Overview

This trial is active, not recruiting.

Conditions chronic myeloproliferative disorders, graft versus host disease, leukemia, lymphoma, multiple myeloma and plasma cell neoplasm, myelodysplastic syndromes, myelodysplastic/myeloproliferative diseases, precancerous/nonmalignant condition
Treatments busulfan, cyclophosphamide, cyclosporine, etoposide, fludarabine phosphate, melphalan, methotrexate, mycophenolate mofetil, sirolimus, tacrolimus, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, total-body irradiation
Phase phase 2
Targets mTOR, FKBP-12
Sponsor City of Hope Medical Center
Collaborator National Cancer Institute (NCI)
Start date September 2001
End date August 2016
Trial size 260 participants
Trial identifier NCT00544115, 01089, CDR0000566376, CHNMC-01089, P30CA033572

Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil, and sirolimus before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor peripheral stem cell transplant works in treating patients with advanced hematologic cancer or other disorders.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
cyclophosphamide
cyclosporine
methotrexate
mycophenolate mofetil
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation
(Active Comparator)
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
busulfan
cyclophosphamide
cyclosporine
methotrexate
mycophenolate mofetil
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
(Active Comparator)
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
cyclosporine
etoposide
methotrexate
mycophenolate mofetil
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation
(Active Comparator)
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
cyclosporine
fludarabine phosphate
melphalan
methotrexate
mycophenolate mofetil
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
(Active Comparator)
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
cyclosporine
fludarabine phosphate
methotrexate
mycophenolate mofetil
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation
(Active Comparator)
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
busulfan
cyclosporine
fludarabine phosphate
methotrexate
mycophenolate mofetil
sirolimus
tacrolimus
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation

Primary Outcomes

Measure
Neutrophil and platelet engraftment
time frame: 180 days post transplant
Incidence of acute and chronic graft-versus-host disease (GVHD)
time frame: 1 year post transplant

Secondary Outcomes

Measure
Impact of HLA class I and class II allele-matching on the incidence of GVHD and on the survival outcome
time frame: 1 year post transplant
Overall survival
time frame: 2 years post transplant
Disease-free survival
time frame: 2 years post transplant
Relapse
time frame: At the time of relapse post transplant

Eligibility Criteria

Male or female participants up to 120 years old.

DISEASE CHARACTERISTICS: - Diagnosis of one of the following: - Acute lymphocytic leukemia (ALL), meeting one of the following criteria: - In first relapse or beyond - High-risk ALL, defined by any of the following: - Hypoploidy (≤ 44 chromosomes) - Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14), excluding B-cell ALL - Elevated WBC at presentation (WBC > 20,000/mm³ [for patients > 18 years of age]; WBC > 200,000/mm³ [for patients 12-18 years of age]) - Acute myeloid leukemia (AML), meeting one of the following criteria: - In first complete remission - Failed to achieve remission - In first relapse or beyond - Secondary AML (> 30% blasts in marrow aspirate) - Should receive induction chemotherapy to obtain remission, if possible, before transplant - Chronic myelogenous leukemia, meeting one of the following criteria: - In first or second chronic phase or accelerated phase - In blast crisis, defined as > 30% promyelocytes plus blasts in the bone marrow - Myelodysplastic syndromes, including any of the following: - Refractory anemia with excess blasts (RAEB) - Chronic myelomonocytic leukemia - RAEB in transformation - Refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, or multiple myeloma - Received and failed front-line therapy, high-dose therapy and autologous stem cell transplantation, or salvage therapy - Myeloproliferative disorders/myelofibrosis may be allowed on a case by case basis - Severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, or any other hematologic disorder requiring transplantation - Patients > 55 years of age with hematologic diseases treatable by allogeneic stem cell transplantation who are not eligible for IRB 99190 are eligible - No uncontrolled CNS involvement of disease - No matched (6/6) related donor available - HLA-identical unrelated donor available - HLA-phenotypically identical for HLA-A and HLA-B alleles and identical for DRB1 alleles by DNA typing for both class I and class II antigens - Allele mismatch for HLA class I (i.e., B 2701 vs B 2702) allowed if no alternative donors - Allele mismatch for class II (i.e., DRB1 0401 vs 0402) or minor mismatch for class I cross reactive group (CREG) (i.e., A 2 vs A 28) allowed in patients ≤ 35 years of age requiring urgent transplant PATIENT CHARACTERISTICS: - Karnofsky performance status 50-100% - Life expectancy > 8 weeks - LVEF ≥ 45% at rest - AST ≤ 2 times normal (unless liver function abnormality is due to underlying disease) - Total bilirubin < 1.5 times normal (unless liver function abnormality is due to underlying disease) - Creatinine ≤ 1.5 times normal OR creatinine clearance ≥ 60 mL/min - DLCO ≥ 40% of predicted (corrected for hemoglobin) - No coexisting medical problem that would significantly increase the risk of the transplant procedure - HIV negative - Not pregnant PRIOR CONCURRENT THERAPY: - See Disease Characteristics

Additional Information

Official title A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Unrelated Donors in Patients With Advanced Hematologic Malignancies and Hematological Disorders
Description OBJECTIVES: Primary - To evaluate hematopoietic recovery, using neutrophil and platelet engraftment as the primary criterion, in patients with advanced hematologic malignancies or other disorders undergoing allogeneic peripheral blood stem cell (PBSC) transplantation from matched unrelated donors. - To evaluate the incidence of acute and chronic graft-versus-host-disease (GVHD) in patients undergoing allogeneic PBSC transplantation from matched unrelated donors. Secondary - To evaluate the impact of HLA class I and class II allele-matching on the incidence of GVHD and on the survival outcome of these patients. - To evaluate overall survival, disease-free survival, and relapse in these patients. OUTLINE: Patients are stratified according to type of conditioning regimen (myeloablative vs reduced-intensity myeloablative). Patients are assigned to a conditioning regimen according to diagnosis, age, disease status, prior radiotherapy, and prior autologous stem cell transplantation. - Conditioning regimen: - Regimen I: Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1. - Regimen II: Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2. - Regimen III: Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3. - Regimen IV: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2. - Regimen V: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0. - Regimen VI: Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2. - Allogeneic peripheral blood stem cell (PBSC) transplantation: All patients undergo allogeneic PBSC transplantation on day 0. - Graft-versus-host disease (GVHD) prophylaxis: Patients receive one of the following GVHD prophylaxis regimens: - Regimen A: Patients receive tacrolimus IV or orally on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11. - Regimen B: Patients receive cyclosporine IV or orally twice daily on days -1 to 180, mycophenolate mofetil IV over 2 hours or orally twice daily on days 0-27, and methotrexate IV on days 1, 3, and 6. - Regimen C: Patients receive tacrolimus IV continuously or orally, and oral sirolimus beginning on day -3. Patients also receive methotrexate IV on days 1, 3, and 6. After completion of study therapy, patients are followed periodically.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by City of Hope Medical Center.