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Completed

NCT Number: NCT02927769

A Study of Nivolumab Plus Brentuximab Vedotin in Patients Between 5 and 30 Years Old, With Hodgkin's Lymphoma (cHL), Relapsed or Refractory From First Line Treatment

The purpose of this study is to determine whether nivolumab plus brentuximab vedotin (followed by brentuximab vedotin plus bendamustine in patient with suboptimal response) is safe and effective in treating patients with Hodgkin's lymphoma (cHL). Eligible patients are children, adolescents, and young adults relapsed or refractory to first line.

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Key information

Conditions

Hodgkin Disease Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

5 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Local Institution, Calgary, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Classic Hodgkin Lymphoma (cHL), relapsed or refractory
  • Minimal limitation on activities of daily living as measured by Karnofsky ≥ 50 for participants > 16 years of age or Lansky ≥ 50 for participants ≤ 16 years of age.
  • One prior anti-cancer therapy that did not work

Exclusion criteria

  • Active, known, or suspected autoimmune disease or infection
  • Active cerebral/meningeal disease related to the underlying malignancy
  • More than one line of anti-cancer therapy or no treatment at all
  • Received a stem cell transplant for Hodgkin Lymphoma and/or a solid organ transplant
  • Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)

Other protocol defined inclusion/exclusion criteria apply

Treatment and study plan

Nivolumab

Biological

Specified Dose on Specified Days

Other names: BMS-936558, Opdivo

Brentuximab Vedotin

Biological

Specified Dose on Specified Days

bendamustine

Biological

Specified Dose on Specified Days

Primary outcomes

  1. Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1

    Time frame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).

    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR.

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease Participants who stopped study treatment early for toxicity without a CMR were evaluable.

    Confidence interval is based on the Clopper and Pearson method

  2. Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1

    Time frame: At 3 years post first dose of study therapy

    Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death .

    PD :

    Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.

    Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.

    New Lesions: Yes Bone Marrow: New or returning FDG-avid disease

    CMR:

    Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy.

    Based on Kaplan-Meier Estimates.

  3. Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Blinded Independent Centralized Review (BICR) - Cohort 2

    Time frame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)

    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR.

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable.

    Confidence interval is based on the Clopper and Pearson method

Secondary outcomes

  1. Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)

    Time frame: From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).

    Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved a best response of complete metabolic response (CMR) or partial metabolic response (PMR).

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease

    Partial metabolic response (PMR):

    • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
    • New lesions: None
    • Bone marrow: Residual uptake higher than normal, reduced from baseline. Participants who came off early for toxicity without CMR or PMR were evaluable.

  2. Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)

    Time frame: At 3 years post first dose of study therapy

    Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by BICR or death.

    Progressive Disease (PD):

    Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.

    Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.

    New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy for R2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.

    Based on Kaplan-Meier Estimates.

  3. Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)

    Time frame: From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)

    Duration of response (DOR) is the time from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, DOR was censored on the date of last tumor assessment.

    Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent therapy.

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease

    Partial metabolic response (PMR):

    • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
    • New lesions: None
    • Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates

  4. Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1

    Time frame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).

    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR.

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease Participants who come off early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method

  5. Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1

    Time frame: At 3 years post first dose of study therapy

    Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death .

    PD :

    Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.

    Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.

    New Lesions: Yes Bone Marrow: New or returning FDG-avid disease

    CMR:

    Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy.

    Based on Kaplan-Meier Estimates.

  6. Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Investigator - Cohort 2

    Time frame: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)

    The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR.

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable.

    Confidence interval is based on the Clopper and Pearson method.

  7. Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator

    Time frame: From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).

    Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieve a best response of complete metabolic response (CMR) or partial metabolic response (PMR).

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease

    Partial metabolic response:

    • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
    • New lesions: None
    • Bone marrow: Residual uptake higher than normal, reduced from baseline Participants who came off early for toxicity without CMR or PMR were evaluable.

  8. Progression Free Survival (PFS) Rate at 3 Years by Investigator

    Time frame: At 3 years post first dose

    Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by investigator or death.

    Progressive Disease (PD):

    Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.

    Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.

    New Lesions: Yes Bone Marrow: New or returning FDG-avid disease. Participants who neither progressed nor died were be censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy forR2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.

    Based on Kaplan-Meier Estimates.

  9. Duration of Response (DOR) by Investigator

    Time frame: From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)

    Duration of response (DOR) is the time from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, the DOR was censored on the date of last tumor assessment.

    Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.

    Complete metabolic response (CMR):

    • Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
    • New lesions: No
    • Bone marrow: No FDG-avid disease

    Partial metabolic response:

    • Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
    • New lesions: None
    • Bone marrow: Residual uptake higher than normal, reduced from baseline. Based on Kaplan-Meier estimates.

  10. The Number of Participants With Adverse Events (AEs)

    Time frame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).

    An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.

  11. The Number of Participants With Serious Adverse Events (SAEs)

    Time frame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)

    A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose:

    • Results in death
    • Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe)
    • Requires inpatient hospitalization or causes prolongation of existing hospitalization
    • Results in persistent or significant disability/incapacity
    • Is a congenital anomaly/birth defect
    • Is an important medical event.

  12. The Number of Participants With Abnormal Laboratory Values for Specific Thyroid Tests

    Time frame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)

    The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests.

  13. The Number of Participants With Abnormal Laboratory Values for Liver Tests

    Time frame: From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)

    The Number of Participants with Abnormal Laboratory Values for Liver Tests.

  14. Number of Participants With Abnormal Vital Signs Reported as Adverse Events

    Time frame: From first dose to 100 days after last dose of study therapy (assessed for an average of 7 months up until a maximum of 10 months).

    Temperature, blood pressure, and heart rate abnormalities reported as adverse events.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Collaborators

  • Seagen Inc.

Registry information

Official study title

Risk-based, Response-adapted, Phase II Open-label Trial of Nivolumab + Brentuximab Vedotin (N + Bv) for Children, Adolescents, and Young Adults With Relapsed/Refractory (R/R) CD30 + Classic Hodgkin Lymphoma (cHL) After Failure of First-line Therapy, Followed by Brentuximab + Bendamustine (Bv + B) for Participants With a Suboptimal Response (CheckMate 744: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation)

Acronym: CheckMate 744

Important dates

Study start
2017
Primary completion
2024
Study completion
2024
First posted
Oct 7, 2016
Registry last updated
Feb 10, 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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