Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

Sponsor

City of Hope Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00544115

Collaborator

National Cancer Institute (NCI) (NIH)

260

Enrollment

Arms

254.5

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Precancerous/Nonmalignant Condition	Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: etoposide Drug: fludarabine phosphate Drug: melphalan Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 16, 2001

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: cyclophosphamide Drug: cyclosporine Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation
Active Comparator: 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.	Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation
Active Comparator: Regimen III Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.	Drug: cyclosporine Drug: etoposide Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation
Active Comparator: Regimen IV Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.	Drug: cyclosporine Drug: fludarabine phosphate Drug: melphalan Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation
Active Comparator: Regimen V Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.	Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation
Active Comparator: Regimen VI Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.	Drug: busulfan Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation

Outcome Measures

Primary Outcome Measures

Neutrophil and platelet engraftment [180 days post transplant]
Incidence of acute and chronic graft-versus-host disease (GVHD) [1 year post transplant]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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