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NCT Number: NCT03104491

Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects.

The Phase II portion of this study is to see what side effects are seen with medication after transplant.

Inotuzumab ozogamicin is a combination of an antibody and chemotherapy which has been shown to have significant activity against relapsed/refractory acute lymphocytic leukemia (ALL).

Inotuzumab ozogamicin is considered experimental in this study.

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Key information

Conditions

Acute Lymphocytic Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

16 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

The University of Kansas Cancer Center, Westwood, Kansas, United States

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About this study

Study Design This is a Phase I/II study of inotuzumab ozogamicin for the treatment of patients who underwent allogeneic transplantation for ALL and have a high risk of relapse. The Phase I portion of this study will be a 3+3 dose escalation trial. This is followed by a phase 2 cohort at the recommended Phase 2 dose (RP2D). Participants will receive study treatment up to 4 cycles until relapse of disease, unacceptable toxicity, or death, whichever occurs first

Phase I: Inotuzumab Ozogamicin Dosing Escalation Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach.

Phase II: Inotuzumab Ozogamicin Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. In order to be included in the safety profile endpoint review, subjects must have received at least of 1 cycle of treatment.

Primary Objective

Phase I: To define a post hematopoietic stem cell transplantation maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of inotuzumab ozogamicin.

Phase II: To assess the efficacy of inotuzumab ozogamicin as measured by diseasefree survival (DFS) at one year.

Secondary Objective(s)

Phase I:

  • To evaluate disease-free survival (DFS), nonrelapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year.
  • To determine safety profile of inotuzumab ozogamicin after transplant including the incidence of myeloid toxicity and secondary graft failure and the rate of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS).
  • To determine if inotuzumab ozogamicin at these doses is effective at eradicating minimal residual disease in this cohort of participants

Phase II:

  • To assess additional evidence of efficacy and safety as measured by non-relapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year.
  • To determine if inotuzumab ozogamicin at these doses is effective at eradicating MRD.
  • To confirm the safety profile of inotuzumab ozogamicin therapy after transplant including myeloid toxicity, secondary graft failure, and the rate of VOD/SOS.
  • To evaluate the pharmacokinetics of inotuzumab ozogamicin post allogeneic transplant

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Phase 1 Inclusion Criteria

  • Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
  • Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • Patients who are between T+40 and T+100 after allogeneic transplantation. Patients must receive their first dose of inotuzumab at or before T+100.
  • Patients who have/are either:
  • Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation

---Pre- or Post-Transplant Minimal Residual Disease defined by:

----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.

  • In second or third complete remission at the time of allogeneic transplantation
  • Treated with reduced intensity regimens or non-myeloablative conditioning regimens
  • Lymphoid blast crisis of CML
  • Are relapsed or refractory to at least 1 line of chemotherapy
  • Philadelphia-like ALL
  • Patients who have evidence of donor chimerism after allogeneic transplantation.
  • ECOG Performance status < 2
  • Participants must have ANC > 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/µL for 7 days.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Participants must have the ability to understand and the willingness to sign a written informed consent document.

Phase 2 Inclusion Criteria

  • Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
  • Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • Patients who are between T+40 and T+100 after allogeneic transplantation
  • Patients who have/are either:
  • Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation

---Post-Transplant Minimal Residual Disease defined by:

----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.

  • In second or third complete remission at the time of allogeneic transplantation
  • Treated with reduced intensity regimens as defined per institutional standard of practice
  • Lymphoid blast crisis of CML
  • Are relapsed or refractory to at least 1 line of chemotherapy
  • Philadelphia-like ALL
  • Patients who have > 80% donor chimerism after allogeneic transplantation.
  • Philadelphia chromosome positive ALL must have failed at least 1 TKI
  • ECOG Performance status < 1
  • pre-transplant evaluation, see 10.1.1
  • Participants must have ANC > 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/µL for 7 days.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Participants must have the ability to understand and the willingness to sign a written informed consent document.

Phase 1 and 2 Exclusion Criteria:

  • Patients with clinical evidence of disease progression prior to enrollment
  • Persistent prior treatment toxicities Grade 2 and above according to NCI CTCAE Version 4.03 (with the exception for alopecia, neuropathy, etc.)
  • Patients with inadequate organ function as defined by:
  • Creatinine clearance < 30ml/min
  • Bilirubin > 2X institutional upper limit of normal
  • AST (SGOT) > 2X institutional upper limit of normal
  • ALT (SGPT) > 2X institutional upper limit of normal
  • GVHD grade III or IV (for patients with a prior allogeneic transplant).
  • Active acute or chronic GVHD of the liver (for patients with a prior allogeneic transplant)
  • History of VOD
  • Use of concomitant TKI or sirolimus
  • Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast)
  • Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or breastfeeding women are excluded from this study because inotuzumab ozogamicin may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with inotuzumab ozogamicin, breastfeeding should be discontinued if the mother is treated with inotuzumab ozogamicin. These potential risks may also apply to other agents used in this study.
  • Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
  • Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
  • Participation in any other investigational drug study or had exposure to any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
  • Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds

Treatment and study plan

Inotuzumab ozogamicin

Drug

Inotuzumab ozogamicin, IV, 28 day cycles

Phase 1 dosages:

Dose Level -2 (0.1 mg/m^2)

Dose Level -1 (0.2 mg/m^2)

Dose Level 0 (0.3 mg/m^2)

Dose Level 1 (0.4 mg/m^2)

Dose Level 2 (0.5 mg/m^2)

Dose Level 3 (0.6 mg/m^2)

Primary outcomes

  1. Phase I MTD

    Time frame: Up to 112 days (16 weeks)

    Defined post hematopoietic stem cell transplantation MTD

  2. Phase I DLTs

    Time frame: Up to 112 days (16 weeks)

    Frequency of DLTs during the first two cycles in ALL-participants

  3. Phase II Median DFS

    Time frame: At 3 months after initial treatment

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  4. Phase II Median DFS

    Time frame: At 6 months after initial treatment

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  5. Phase II Median DFS

    Time frame: At 9 months after initial treatment

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  6. Phase II Median DFS

    Time frame: At 1 year after initial treatment

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  7. Phase II Median DFS

    Time frame: Post first dose of inotuzumab ozogamicin

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

Secondary outcomes

  1. Phase I Median DFS

    Time frame: At 3 months after initial treatment

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  2. Phase I Median DFS

    Time frame: At 6 months after initial treatment

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  3. Phase I Median DFS

    Time frame: At 9 months after initial treatment

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  4. Phase I Median DFS

    Time frame: At 1 year after initial treatment

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  5. Phase I Median DFS

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  6. Phase I NRM

    Time frame: At 3 months after initial treatment

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  7. Phase I NRM

    Time frame: At 6 months after initial treatment

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  8. Phase I NRM

    Time frame: At 9 months after initial treatment

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  9. Phase I NRM

    Time frame: At 1 year after initial treatment

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  10. Phase I NRM

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Phase I NRM , defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  11. Phase I Relapse

    Time frame: At 3 months after initial treatment

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  12. Phase I Relapse

    Time frame: At 6 months after initial treatment

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  13. Phase I Relapse

    Time frame: At 9 months after initial treatment

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  14. Phase I Relapse

    Time frame: At 1 year after initial treatment

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  15. Phase I Relapse

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  16. Phase I Relapse-related mortality

    Time frame: At 3 months after initial treatment

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  17. Phase I Relapse-related mortality

    Time frame: At 6 months after initial treatment

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  18. Phase I Relapse-related mortality

    Time frame: At 9 months after initial treatment

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  19. Phase I Relapse-related mortality

    Time frame: At 1 year after initial treatment

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  20. Phase I Relapse-related mortality

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  21. Phase I Median OS

    Time frame: At 3 months after initial treatment

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  22. Phase I Median OS

    Time frame: At 6 months after initial treatment

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  23. Phase I Median OS

    Time frame: At 9 months after initial treatment

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  24. Phase I Median OS

    Time frame: At 1 year after initial treatment

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  25. Phase I Median OS

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  26. Phase I Incidence of myeloid toxicity

    Time frame: At 1 year

    Number of patients who develop myeloid toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia CTCAE 4

  27. Phase I Incidence of secondary graft failure

    Time frame: At 1 year

    Number of patients who develop secondary graft failure while on study, defined as:

    Either cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced

  28. Phase I incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS)

    Time frame: At 1 year

    Safety profile of intervention as measured by incidence of VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

  29. Phase I rate of VOD/SOS - number of participants affected

    Time frame: At 1 year

    Safety profile of intervention as measured by number of participants affected by VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

  30. Phase I - Percent of participants with grade 3 + AE/SAEs

    Time frame: At 1 year

    Phase I safety profile of intervention as measured by percent of participants with grade 3 + AE/SAEs

  31. Phase II Non-relapse mortality (NRM)

    Time frame: At 3 months after initial treatment

    Phase II Non-relapse mortality (NRM), defined as time from date of first dose to death due to any cause without prior relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  32. Phase II Relapse

    Time frame: At 6 months after initial treatment

    Phase II relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  33. Phase II Relapse

    Time frame: At 9 months after initial treatment

    Phase II relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  34. Phase II Relapse-related mortality

    Time frame: At 1 year after initial treatment

    Phase II Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  35. Phase II Relapse-related mortality

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Phase II Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

  36. Phase II Median OS

    Time frame: At 3 months after initial treatment

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  37. Phase II Median OS

    Time frame: At 6 months after initial treatment

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  38. Phase II Median OS

    Time frame: At 9 months after initial treatment

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  39. Phase II Median OS

    Time frame: At 1 year after initial treatment

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  40. Phase II Median OS

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

  41. Phase II Response Rate

    Time frame: At 3 months after initial treatment

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

  42. Phase II Response Rate

    Time frame: At 6 months after initial treatment

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

  43. Phase II Response Rate

    Time frame: At 9 months after initial treatment

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

  44. Phase II Response Rate

    Time frame: At 1 year after initial treatment

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

  45. Phase II Response Rate

    Time frame: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

  46. Phase II Incidence of myeloid toxicity

    Time frame: At 1 year

    Number of patients who develop myeloid toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia CTCAE 4

  47. Phase II Incidence of secondary graft failure

    Time frame: At 1 year after initial treatment

    Number of patients who develop secondary graft failure while on study, defined as:

    Either cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced

  48. Phase I incidence of VOD/SOS

    Time frame: At 1 year

    Safety profile of intervention as measured by incidence of VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

  49. Phase II rate of VOD/SOS - number of participants affected

    Time frame: At 1 year

    Safety profile of intervention as measured by number of participants affected by VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

  50. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  51. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 1 (C1D1) after 1 hour (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  52. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 1 (C1D1) after 4 hours (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  53. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 1 Day 7 (C1D7) (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  54. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  55. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  56. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  57. Phase II pharmacokinetic (PK) parameters - Cmax

    Time frame: At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days)

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  58. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  59. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle1 Day 1 (C1D1) after 1 hour (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  60. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle1 Day 1 (C1D1) after 4 hours (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  61. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 1 Day 7 (C1D7) (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  62. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  63. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  64. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

  65. Phase II pharmacokinetic (PK) parameters - Ctrough

    Time frame: At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days)

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

Study contacts

Contact information is provided by the study sponsor or research team.

Leland Metheny, MD

CONTACT

[email protected]

1-800-641-2422

Ron Sobecks, MD

CONTACT

[email protected]

216-444-6833

Sponsors and collaborators

Lead sponsor

Leland Metheny

Other

Registry information

Important dates

Study start
2017
Primary completion
2025
Study completion
2027
First posted
Apr 7, 2017
Registry last updated
Jun 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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