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NCT Number: NCT01839916

Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

This pilot phase II trial studies how well giving donor T cells after donor stem cell transplant works in treating patients with hematologic malignancies. In a donor stem cell transplant, the donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.

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Key information

Conditions

Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blast Crisis Blastic Phase Chronic Myelogenous Leukemia Blood Protein Disorders Bone Marrow Diseases Burkitt Lymphoma Carcinogenesis Cardiovascular Diseases Cell Transformation, Neoplastic Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Disease Chronic Phase Chronic Myelogenous Leukemia Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cutaneous B-cell Non-Hodgkin Lymphoma DNA Virus Infections Dendritic Cell Sarcoma, Interdigitating Disease Attributes Epstein-Barr Virus Infections Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Eye Neoplasms Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hepatosplenic T-cell Lymphoma Herpesviridae Infections Histiocytic Disorders, Malignant Histiocytosis Hodgkin Disease Immune System Diseases Immunoblastic Lymphadenopathy Immunoproliferative Disorders Infections Intraocular Lymphoma Leukemia Leukemia, B-Cell Leukemia, Hairy Cell Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myeloid, Acute Leukemia, Myeloid, Chronic-Phase Leukemia, T-Cell Lymphadenopathy Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Lymphoproliferative Disorders Mycosis Fungoides Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Plasma Cell Neoplastic Processes Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Previously Treated Myelodysplastic Syndromes Recurrence Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Grade III Lymphomatoid Granulomatosis Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Relapsing Chronic Myelogenous Leukemia Secondary Myelodysplastic Syndromes Sezary Syndrome Small Intestine Lymphoma Splenic Marginal Zone Lymphoma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Tumor Virus Infections Vascular Diseases Virus Diseases Waldenstrom Macroglobulinemia Waldenström Macroglobulinemia de Novo Myelodysplastic Syndromes

Age range

14 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637-1470, United States

About this study

PRIMARY OBJECTIVES:

I. To determine the feasibility of escalating dose regimen (EDR) donor lymphocyte infusion (DLI) as measured by the proportion of patients who receive at least one DLI.

SECONDARY OBJECTIVES:

I. To assess progression free survival (PFS) at 2 years after stem cell transplant (SCT) for high-risk hematologic malignancies receiving T-cell depleted grafts followed by escalating dose regimen (EDR) prophylactic DLI compared to historical controls not receiving DLI.

II. To assess the safety of EDR DLI for high-risk hematologic malignancies as measured by cumulative incidence of severe grade III-IV acute graft-versus-host disease (GVHD).

III. To measure outcomes of grade II-IV acute GVHD, non-relapse mortality, overall survival and chronic GVHD of EDR DLI.

IV. To assess the full donor chimerism rate in the CD3 compartment and immune reconstitution after EDR DLI.

OUTLINE:

Patients receive DLI intravenously (IV). Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 2 years.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • INCLUSION CRITERIA PRIOR TO TRANSPLANT:
  • The clinical trial will be offered to all high risk (defined 3 below) patients with hematologic malignancies who require stem cell transplants as part of their standard of care using matched related or unrelated donors
  • Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following American Society for Blood and Marrow Transplantation (ASBMT) criteria, including but not limited to conditions listed; these criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning:
  • Refractory acute myelogenous or lymphoid leukemia
  • Relapsed acute myelogenous or lymphoid leukemia
  • Myelodysplastic syndromes with 5% or more blasts
  • Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase
  • Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant
  • High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen
  • DONORS: Matched related or unrelated donor stem cell transplant (SCT) matched at human leukocyte antigen (HLA) A- B, C, and DRB1 by molecular methods; 7 of 8 matched donor acceptable for related donors
  • T-cell depletion with anti-thymocyte globulin (ATG) (rabbit or horse) or at least 30 mg of alemtuzumab total in the conditioning regimen
  • Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant
  • Zubrod performance status (PS) 0-2 or equivalent Karnofsky PS
  • Eligible for allogeneic transplant in the treating physicians' judgment and by institutional standards
  • ELIGIBILITY TO RECEIVE DLI POST-TRANSPLANT:
  • Donor lymphocytes available or able to be collected
  • No evidence of disease by standard morphology; minimal residual disease or molecular evidence of disease will not exclude
  • Absolute neutrophil count >= 500/μl
  • Platelet count >= 20,000/μl without transfusion for 7 days
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 5 x upper limit of normal (ULN)
  • Bilirubin =< 3 x ULN
  • No evidence of grade II or higher acute GVHD or chronic GVHD at initiation of first DLI
  • No systemic corticosteroids or immunosuppressive drugs (topical acceptable); replacement steroids for adrenal insufficiency are not excluded

Exclusion criteria

  • EXCLUSION CRITERIA PRIOR TO TRANSPLANT:
  • Pregnant or lactating females
  • Hepatitis B with positive viral load prior to transplant conditioning or hepatitis C virus
  • Human immune deficiency virus
  • Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent
  • Creatinine >= 2.0 mg/dL
  • SGOT and SGPT >= 5 x ULN; liver biopsy preferred for such patients
  • Bilirubin >= 3 x ULN (unless Gilbert's syndrome)
  • Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% corrected for hemoglobin
  • Left ventricular ejection fraction or shortening fraction < 40%
  • Unlikely to be able to procure additional donor lymphocytes

Treatment and study plan

therapeutic allogeneic lymphocytes

Biological

Given IV

Other names: ALLOLYMPH

laboratory biomarker analysis

Other

Correlative studies

Primary outcomes

  1. Percentage of Patients Who Are Able to Receive at Least One DLI Treatment

    Time frame: Up to 2 years

Secondary outcomes

  1. Progression Free Survival (PFS)

    Time frame: 2 years

    Time to relapse or death as a result of any cause was evaluated at 2 years and the progression free survival rate was reported.

  2. Overall Survival (OS)

    Time frame: At 2 years

    Computed using the Kaplan-Meier product-limit estimate and expressed as probabilities with a 95% CI.

  3. Rate of Acute GVHD (aGVHD) With Any Grade

    Time frame: At 1 year and 2 year

    Estimated by cumulative incidence method.

  4. Rate of Chronic GVHD (cGVHD)

    Time frame: At 1 year and 2 year

    Estimated by cumulative incidence method.

  5. Treatment-related Mortality

    Time frame: At 2 year

    Estimated by cumulative incidence method. Cumulative incidence of treatment-related mortality with relapse of the original disease as the competing risk will be calculated.

Sponsors and collaborators

Lead sponsor

University of Chicago

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study title

Pilot Study of Prophylactic Dose-Escalation Donor Lymphocyte Infusion After T Cell Depleted Allogeneic Stem Cell Transplant in High Risk Patients With Hematologic Malignancies

Important dates

Study start
2013
Primary completion
2018
Study completion
2018
First posted
Apr 25, 2013
Registry last updated
Aug 7, 2019

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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