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

NCT ID: NCT01839916

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-04
• Study Completion Date: 2018-08-31

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.

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; 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (DLI)

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

Group Type: EXPERIMENTAL

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

therapeutic allogeneic lymphocytes

Given IV

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

ALLOLYMPH

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hongtao Liu

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2013-00782

Identifier Type: REGISTRY

Identifier Source: secondary_id

12-1191

Identifier Type: -

Identifier Source: org_study_id