Status:
COMPLETED
T-Cell-Depleted Allogeneic Stem Cell Transplantation After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Hematologic Malignancies
Lead Sponsor:
National Institutes of Health Clinical Center (CC)
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Chronic Myeloproliferative Disorders
Leukemia
Eligibility:
All Genders
18-55 years
Phase:
PHASE1
Brief 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 rejecte...
Detailed Description
OBJECTIVES: Primary * Determine engraftment in patients with hematologic malignancies treated with T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy an...
Eligibility Criteria
Inclusion
- 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
Exclusion
Key Trial Info
Start Date :
February 1 2004
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2010
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT00080925
Start Date
February 1 2004
End Date
December 1 2010
Last Update
March 8 2012
Active Locations (1)
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1
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182