Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression
18 Years
75 Years
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Trial Information
Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression
OBJECTIVES:
- Determine a minimal (short-duration) post-transplant immunosuppression regimen
comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus
that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease
(GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic
bone marrow or peripheral blood stem cell transplantation from an HLA-identical related
donor.
- Determine the post-transplant immunosuppression regimen that results in < 10% incidence
of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in
these patients.
- Determine the incidence and severity of acute GVHD in patients treated with these
regimens.
- Determine the frequency of mixed chimerism in patients treated with these regimens.
OUTLINE:
- Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem
cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and
undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or
PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF)
beginning on day 5 and continuing until at least day 15 or until blood counts recover.
- Sequentially increasing levels of post-transplant immunosuppression: Cohorts of
patients are enrolled into 1 of the following regimens:
- Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on
day 3 only.
- Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil
(MMF) once on day 3 and then twice daily on days 4-32.
- Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on
days 3 and 4 and MMF twice daily on days 4-33.
- Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and
MMF as in regimen 3.
- Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and
MMF as in regimen 3 and tacrolimus twice daily on days 4-33.
Cohorts of approximately 10-20 patients receive sequentially increasing levels of
post-transplant immunosuppression until a minimal (short-duration) post-transplant
immunosuppression regimen is identified. The minimal post-transplant immunosuppression
regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II
or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to
engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression
regimen is identified, an additional 10 patients are treated with that regimen.
Patients are followed for 60 days after transplantation.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following hematologic malignancies:
- Stage II or III multiple myeloma
- Amyloidosis
- Myelofibrosis with ≥ 2 of the following high-risk features:
- Over 55 years of age
- Hemoglobin < 10 g/dL
- WBC < 3,000/mm^3 OR > 10,000/mm^3
- Platelet count < 100,000/mm^3
- Cytogenetic abnormalities
- Mycosis fungoides, meeting 1 of the following criteria:
- Stage IIB or III disease with evidence of histologic conversion to an
aggressive lymphoma
- Must demonstrate chemosensitivity
- Stage IV disease
- Paroxysmal nocturnal hemoglobinuria
- Not meeting criteria for other bone marrow transplantation (BMT) or
treatment studies
- Diagnosis of 1 of the following hematologic malignancies, for which patient is
not eligible for potentially curative allogeneic BMT due to end-organ
dysfunction, age 65 to 75, or the amount of prior chemotherapy:
- Acute myeloid or acute lymphoblastic leukemia
- High-risk disease in first or second (or further) complete remission
- Relapsed aggressive non-Hodgkin's lymphoma
- Not eligible for autologous or standard allogeneic BMT
- Hodgkin's lymphoma in second or further complete or partial remission
- Not eligible for autologous or standard allogeneic BMT
- Myelodysplastic syndromes or myelodysplastic/myeloproliferative diseases
- Any of the following subtypes:
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
- Any morphologic subtype with multiple chromosomal abnormalities
- Any subset with life-threatening cytopenias in all 3 cell lines,
defined as platelet count ≤ 20,000/mm^3, absolute neutrophil
count ≤ 500/mm^3, and reticulocyte count ≤ 50,000/mm^3
- Meets both of the following criteria:
- Less than 20% blasts by bone marrow biopsy
- Not eligible for standard allogeneic BMT
- No refractory anemia with ringed sideroblasts
- No 5q syndrome
- Stage III or IV chronic lymphocytic leukemia
- Not meeting criteria for other BMT studies
- Chronic myelogenous leukemia in first or second chronic phase
- Not meeting criteria for other BMT studies or treatment
- Stage III or IV indolent small lymphocytic or follicular lymphoma
- Not eligible for autologous or standard allogeneic BMT or other active
protocols at Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins
- Must have an HLA-identical related donor available
PATIENT CHARACTERISTICS:
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 3.0 mg/dL
- AST ≤ 175 U/L
- ALT ≤ 200 U/L
Renal
- Creatinine ≤ 3.0 mg/dL
Cardiovascular
- LVEF ≥ 30%
Pulmonary
- FEV_1 ≥ 40% predicted
- Forced vital capacity ≥ 40% predicted
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
PRIOR CONCURRENT THERAPY:
Chemotherapy
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant
Principal Investigator
Carol A. Huff, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000449652
NCT ID:
NCT00255710
Start Date:
July 2002
Completion Date:
Related Keywords:
- Chronic Myeloproliferative Disorders
- Graft Versus Host Disease
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Diseases
- graft versus host disease
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute lymphoblastic leukemia in remission
- adult acute myeloid leukemia in remission
- chronic idiopathic myelofibrosis
- chronic myelomonocytic leukemia
- chronic phase chronic myelogenous leukemia
- myelodysplastic/myeloproliferative disease, unclassifiable
- previously treated myelodysplastic syndromes
- recurrent adult Burkitt lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- stage II multiple myeloma
- stage III adult Hodgkin lymphoma
- stage III chronic lymphocytic leukemia
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III multiple myeloma
- stage III small lymphocytic lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV chronic lymphocytic leukemia
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV small lymphocytic lymphoma
- stage II mycosis fungoides/Sezary syndrome
- stage III mycosis fungoides/Sezary syndrome
- stage IV mycosis fungoides/Sezary syndrome
- refractory anemia with excess blasts in transformation
- refractory anemia with excess blasts
- refractory cytopenia with multilineage dysplasia
- primary systemic amyloidosis
- de novo myelodysplastic syndromes
- secondary acute myeloid leukemia
- secondary myelodysplastic syndromes
- atypical chronic myeloid leukemia
- Neoplasms
- Graft vs Host Disease
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
