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

Phase 2

Completed

• Conditions: Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Secondary Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Interventions: Biological: therapeutic allogeneic lymphocytes; Other: laboratory biomarker analysis

• Registration Number: NCT01839916
• Lead Sponsor: University of Chicago

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2013-04-04
• Study First Submitted: 2013-04-22
• Study First Submitted QC: 2013-04-22
• Study First Posted: 2013-04-25
• Primary Completion: 2018-08
• Study Completion: 2018-08
• Status Verified: 2019-06
• Results First Submitted: 2019-06-12
• Results First Submitted QC: 2019-07-17
• Last Update Submitted: 2019-07-17
• Results First Posted: 2019-08-07
• Last Update Posted: 2019-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 77

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (DLI)	therapeutic allogeneic lymphocytes	Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
Treatment (DLI)	laboratory biomarker analysis	Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Who Are Able to Receive at Least One DLI Treatment	Up to 2 years

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	At 2 years	Computed using the Kaplan-Meier product-limit estimate and expressed as probabilities with a 95% CI.
Rate of Acute GVHD (aGVHD) With Any Grade	At 1 year and 2 year	Estimated by cumulative incidence method.
Treatment-related Mortality	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.
Rate of Chronic GVHD (cGVHD)	At 1 year and 2 year	Estimated by cumulative incidence method.
Progression Free Survival (PFS)	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.

Trial Locations

Locations (1)

University of Chicago Comprehensive Cancer Center; 🇺🇸 Chicago, Illinois, United States