Overview

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