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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01839916
Recruitment Status : Completed
First Posted : April 25, 2013
Results First Posted : August 7, 2019
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Chicago

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Blastic Phase Chronic Myelogenous Leukemia 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 Phase Chronic Myelogenous Leukemia Cutaneous B-cell Non-Hodgkin Lymphoma de Novo Myelodysplastic Syndromes Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes 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 Small Intestine Lymphoma Splenic Marginal Zone Lymphoma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Waldenström Macroglobulinemia Biological: therapeutic allogeneic lymphocytes Other: laboratory biomarker analysis Phase 2

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : April 4, 2013
Actual Primary Completion Date : August 2018
Actual Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Organ Donation
Genetic and Rare Diseases Information Center resources: Lymphosarcoma B-cell Lymphoma Follicular Lymphoma Diffuse Large B-Cell Lymphoma Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Marginal Zone Lymphoma Myelodysplastic Syndromes Cutaneous T-cell Lymphoma Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Peripheral T-cell Lymphoma Extranodal Nasal NK/T Cell Lymphoma Hodgkin Lymphoma Acute Graft Versus Host Disease Anaplastic Large Cell Lymphoma Chronic Myeloid Leukemia Childhood Acute Lymphoblastic Leukemia Waldenstrom Macroglobulinemia Burkitt Lymphoma Chronic Graft Versus Host Disease Post-transplant Lymphoproliferative Disease Mycosis Fungoides Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Hairy Cell Leukemia Aggressive NK Cell Leukemia T-cell Large Granular Lymphocyte Leukemia Adult T-cell Leukemia/lymphoma Sezary Syndrome Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Leukemia, T-cell, Chronic Lymphomatoid Granulomatosis Chronic Myeloproliferative Disorders

Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment (DLI)
Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
 Biological: therapeutic allogeneic lymphocytes
Given IV
Other Name: ALLOLYMPH

Other: laboratory biomarker analysis
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Patients Who Are Able to Receive at Least One DLI Treatment [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   14 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01839916


Locations
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United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
University of Chicago
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Hongtao Liu University of Chicago Comprehensive Cancer Center
  Study Documents (Full-Text)

Documents provided by University of Chicago:
Study Protocol and Statistical Analysis Plan  [PDF] June 12, 2019

More Information
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01839916    
Other Study ID Numbers: 12-1191
NCI-2013-00782 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: April 25, 2013    Key Record Dates
Results First Posted: August 7, 2019
Last Update Posted: August 7, 2019
Last Verified: June 2019
Additional relevant MeSH terms:
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Burkitt Lymphoma
Mycoses
Lymphoma
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Follicular
Preleukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Mantle-Cell
 Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, B-Cell, Marginal Zone
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Hematologic Neoplasms
Mycosis Fungoides
Sezary Syndrome
Leukemia, T-Cell
Lymphoma, T-Cell, Cutaneous
Waldenstrom Macroglobulinemia
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, Large-Cell, Anaplastic