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

The University of Chicago

Status and phase: Completed; Phase 2

Conditions: Cutaneous B-cell Non-Hodgkin Lymphoma; Childhood Burkitt Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Splenic Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Childhood Myelodysplastic Syndromes; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Post-transplant Lymphoproliferative Disorder; Small Intestine Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Angioimmunoblastic T-cell Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Childhood Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Waldenström Macroglobulinemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Recurrent Small Lymphocytic Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Accelerated Phase Chronic Myelogenous Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Hepatosplenic T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Refractory Hairy Cell Leukemia; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Recurrent Childhood Acute Lymphoblastic Leukemia; Previously Treated Myelodysplastic Syndromes; Anaplastic Large Cell Lymphoma; Relapsing Chronic Myelogenous Leukemia; Recurrent Adult Diffuse Mixed Cell Lymphoma; Testicular Lymphoma; Recurrent Childhood Acute Myeloid Leukemia; Refractory Chronic Lymphocytic Leukemia; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Noncutaneous Extranodal Lymphoma; Intraocular Lymphoma; Adult Acute Myeloid Leukemia With Del(5q); Childhood Nasal Type Extranodal NK/T-cell Lymphoma; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Diffuse Large Cell Lymphoma; Secondary Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Recurrent Childhood Lymphoblastic Lymphoma; Childhood Diffuse Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult T-cell Leukemia/Lymphoma; Peripheral T-cell Lymphoma

Treatments: Biological: therapeutic allogeneic lymphocytes; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01839916

12-1191

NCI-2013-00782 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 77 patients

Sex: All

Ages: 14 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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77 participants in 1 patient group

Treatment (DLI)

Experimental group

Description:

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

Treatment:

Other: laboratory biomarker analysis

Biological: therapeutic allogeneic lymphocytes