T-Cell-Depleted Allogeneic Stem Cell Transplantation After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Hematologic Malignancies
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms |
Biological: filgrastim Biological: graft-versus-tumor induction therapy Biological: rituximab Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: cyclosporine Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide Drug: fludarabine phosphate Drug: prednisone Drug: vincristine sulfate Procedure: peripheral blood stem cell transplantation |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | T-Cell Depleted, Reduced-Intensity Allogeneic Stem Cell Transplantation From Haploidentical Related Donors For Hematologic Malignancies |
| Estimated Enrollment: | 20 |
| Study Start Date: | February 2004 |
| Study Completion Date: | December 2010 |
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Maryland | |
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | |
| Bethesda, Maryland, United States, 20892-1182 | |
| Study Chair: | Michael R. Bishop, MD | National Cancer Institute (NCI) |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00080925 History of Changes |
| Other Study ID Numbers: | 040116, 04-C-0116, CDR0000357432 |
| Study First Received: | April 7, 2004 |
| Last Updated: | March 7, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
prolymphocytic leukemia accelerated phase chronic myelogenous leukemia chronic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia refractory chronic lymphocytic leukemia de novo myelodysplastic syndromes myelodysplastic/myeloproliferative neoplasm, unclassifiable previously treated myelodysplastic syndromes secondary myelodysplastic syndromes secondary acute myeloid leukemia recurrent adult Hodgkin lymphoma refractory anemia with excess blasts refractory multiple myeloma primary myelofibrosis recurrent adult diffuse large cell lymphoma |
recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent adult Burkitt lymphoma recurrent mantle cell lymphoma adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission chronic myelomonocytic leukemia polycythemia vera essential thrombocythemia stage II multiple myeloma |
Additional relevant MeSH terms:
|
Neoplasms Leukemia Lymphoma Multiple Myeloma Neoplasms, Plasma Cell Plasmacytoma Myelodysplastic Syndromes Preleukemia Myeloproliferative Disorders Hematologic Neoplasms Myelodysplastic-Myeloproliferative Diseases Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Bone Marrow Diseases Precancerous Conditions Neoplasms by Site Cyclophosphamide Cyclosporins Cyclosporine Cytarabine |
ClinicalTrials.gov processed this record on May 16, 2013