T-Cell-Depleted Allogeneic Stem Cell Transplantation After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Hematologic Malignancies

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Donor peripheral stem cell transplantation may be able to replace bone marrow and immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor are rejected by the body's normal cells. Eliminating the T cells from the donor cells before transplanting them and giving cyclosporine may prevent this from happening.

PURPOSE: This phase I trial is studying the side effects of T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning (chemotherapy) in treating patients with hematologic malignancies.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Cyclosporine; Cyclosporins; Cytarabine; Doxorubicin; Etoposide; Fludarabine; Fludarabine phosphate; Liposomal doxorubicin; Prednisone; Rituximab; Vincristine

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

• Acute myeloid leukemia (AML), meeting 1 of the following criteria:

• In first complete remission (CR1), meeting 1 of the following criteria:

• Adverse cytogenetics with minimal residual disease detectable by flow cytometry, cytogenetic analysis, fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR), defined as 1 of the following:

• Complex karyotype [≥ 3 abnormalities]

• inv(3) or t(3;3)

• t(6;9)

• t(6;11)

• Monosomy 7

• Trisomy 8, alone or with an abnormality other than t(8;21), t(9;11), inv(16), or t(16;16)

• t(11;19) (q23;p13.1)

• Failed to achieve CR after primary induction chemotherapy

• Secondary AML

• In second or subsequent remission (CR2 or greater)

• Acute lymphoblastic leukemia, meeting 1 of the following criteria:

• In CR1, meeting 1 of the following criteria:

• Adverse cytogenetics with minimal residual disease detectable by flow cytometry, cytogenetic analysis, FISH, or PCR, defined as the following:

• Translocations involving 11q23, t(9;22), or bcr-abl rearrangement

• Failed to achieve CR after primary induction chemotherapy

• In CR2, if CR1 was < 12 months

• In CR3 or greater

• Myelodysplastic syndromes (MDS)

• INT-2 or high-risk by International Prognostic Scoring System

• No MDS with Fanconi anemia

• Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

• Accelerated phase with treatment failure after imatinib mesylate

• Blast phase

• Myeloproliferative disorders, meeting 1 of the following criteria:

• Agnogenic myeloid metaplasia with adverse-risk features, meeting at least 2 of the following criteria:

• Hemoglobin < 10 g/dL or > 10g/dL if transfusion-dependent

• WBC < 4,000/mm^3 OR > 30,000/mm^3 OR requires cytoreductive therapy to maintain WBC < 30,000/mm^3

• Abnormal cytogenetics, including +8, 12p-

• Polycythemia vera or essential thrombocythemia in transformation to secondary AML

• Myelodysplastic/myeloproliferative disease

• Chronic myelomonocytic leukemia

• Hodgkin's lymphoma or non-Hodgkin's lymphoma

• Refractory lymphoma with progressive disease during combination chemotherapy

• Relapse after OR ineligible for autologous stem cell transplantation (SCT)

• Chronic lymphocytic leukemia

• Treatment failure* after fludarabine, chlorambucil, and at least 1 other salvage regimen

• Prolymphocytic leukemia (PLL), meeting 1 of the following criteria:

• T-PLL

• Treatment failure* after alemtuzumab and at least 1 other regimen

• B-PLL

• Treatment failure* after fludarabine and at least 1 other salvage regimen

• Multiple myeloma, meeting 1 of the following criteria:

• Relapse after autologous SCT

• Plasma cell leukemia

• Adverse cytogenetics, defined as 1 of the following:

• del(13q) = 11q translocation NOTE: *Treatment failure is defined as relapse within 6 months OR failure to achieve remission

• Less than 10% blasts in bone marrow and no circulating blasts in peripheral blood for the following diagnoses:

• Primary or secondary leukemia

• Refractory anemia with excess blasts

• CML

• Other eligible diagnosis in transformation to acute leukemia

• Expected survival of approximately 1 year or less with conventional therapy

• No active CNS involvement by malignancy*

• Prior CNS involvement with no current evidence of CNS malignancy allowed NOTE:

*Active CNS malignancy is defined by lymphoma: tumor mass on CT scan or leptomeningeal disease OR leukemia: blasts present on cerebrospinal fluid cytospin

• Availability of a donor who is a sibling, parent, or offspring who shares 1 full haplotype (HLA-A, -B, or -DR)

• Recipient and donor must have at least a 2-antigen disparity in either the host-versus-graft or graft-versus-host direction

• Parent or offspring donor who is mismatched for a single HLA antigen (i.e., 5/6 HLA) is allowed

• No sibling donor who is 6/6 HLA-matched OR mismatched for a single HLA antigen (i.e., 5/6 HLA)

• No unrelated donor identified in a prior or current National Marrow Donor Program registry search

PATIENT CHARACTERISTICS:

Age

• 18 to 55

Performance status

• ECOG 0-2 OR

• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

• See Disease Characteristics

• Absolute neutrophil count ≥ 1,000/mm^3*

• Platelet count ≥ 20,0000/mm^3* (without transfusion) NOTE: *Lower values may be accepted at the discretion of the principal investigator or study chairperson if due to bone marrow involvement by malignancy

Hepatic

• ALT and AST ≤ 2.5 times upper limit of normal (ULN)*

• Bilirubin ≤ 2.5 times ULN*

• Unconjugated hyperbilirubinemia consistent with Gilbert's syndrome allowed

• No chronic active hepatitis B infection

• Hepatitis B core antibody positive allowed provided patient is surface antigen negative and has no evidence of active infection

• No hepatitis C viral infection

• Seronegative for anti-hepatitis C antibody and detectable hepatitis C viral RNA by reverse transcriptase-polymerase chain reaction assay NOTE: *Higher levels may be accepted at the discretion of the principle investigator or study chairperson if such elevations are due to liver involvement by malignancy

Renal

• Creatinine ≤ 1.5 mg/dL OR

• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• LVEF ≥ 45%

Pulmonary

• DLCO ≥ 50% of expected value (corrected for blood hemoglobin level and alveolar volume)

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 1 year after study participation

• HIV negative

• No active infection not responding to antimicrobial therapy

• No psychiatric disorder that would preclude study compliance or informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• At least 2 weeks since prior monoclonal antibody therapy

Chemotherapy

• See Disease Characteristics

• At least 2 weeks since prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Recovered from all prior therapy

• No administration of tyrosine kinase (TK) inhibitors, including imatinib mesylate and dasatinib, during the conditioning regimen; TK inhibitor administration may resume 28 days after transplantation