Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide
N/A
70 Years
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Trial Information
Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide
OBJECTIVES:
- Determine the minimum effective dose of pretransplant cyclophosphamide to induce
engraftment of haploidentical allogeneic bone marrow without the use of myeloablative
conditioning in patients with hematologic malignancies.
- Determine the incidence and severity of graft versus host disease and nonhematologic
toxicities with this treatment regimen in these patients.
- Correlate the pretreatment phenotypic and functional immunologic characteristics in
these patients in relation to risk of graft rejection with this treatment regimen.
OUTLINE: This is a dose-escalation study of cyclophosphamide.
Patients receive fludarabine IV over 1 hour on days -6 to -2; cyclophosphamide IV over 1
hour on days -6, -5, and 3; total body irradiation on day -1; and allogeneic bone marrow
transplantation on day 0. Patients also receive tacrolimus IV or orally twice a day on days
4-50; oral mycophenolate mofetil on days 4-35; and filgrastim (G-CSF) subcutaneously or IV
starting on day 4 and continuing until blood counts recover.
Cohorts of 3-6 patients receive escalating doses of cyclophosphamide until the minimum
effective dose necessary to induce chimerism without unacceptable toxicity in these patients
is determined.
Patients are followed at 2 and 6 months, at one year, and then annually thereafter.
PROJECTED ACCRUAL: At least 23 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Patients with any of the following diagnoses:
- Chronic myelogenous leukemia
- Chronic phase 1
- Failed prior interferon alfa therapy OR
- Relapsed after prior autologous stem cell transplantation
- Chronic phase 2
- Acute leukemia
- Standard risk
- Age over 60 years
- Complete remission 1 (CR1)
- High risk
- High WBC at presentation, unfavorable cytogenetics, mixed lineage,
delayed response to induction chemotherapy
- CR1
- Complete remission 2 or higher
- Acute lymphocytic leukemia
- CR1 or higher
- Myelodysplastic syndrome
- Untreated OR
- CR1
- Acute myeloid leukemia in CR1
- Chronic lymphocytic leukemia
- Rai stage III or IV OR
- Received prior autologous stem cell transplantation
- Multiple myeloma
- Stage II or III
- Stable or progressive disease after prior chemotherapy OR
- Received prior autologous stem cell transplantation
- Non-Hodgkin's Lymphoma
- Hodgkin's lymphoma
- Ineligible for or refused autologous or standard allogeneic bone marrow
transplantation
- Ineligible for bone marrow transplantation from an HLA matched, sibling donor or from
an HLA matched, unrelated donor
- Must have an HLA mismatched, related donor (3-5 out of 6)
PATIENT CHARACTERISTICS:
Age:
- 0.5 to 70
Performance status:
- ECOG 0-1
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin less than 3.1 mg/dL
Renal:
- Not specified
Cardiovascular:
- Left ventricular ejection fraction at least 35%
Pulmonary:
- FEV_1 and FVC at least 40% of predicted OR
- FEV_1 and FVC at least 60% in patients who have received prior thoracic or mantle
radiotherapy
Other:
- HIV negative
- No other debilitating medical or psychiatric illness that would preclude study
compliance
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- No prior transfusions from donor
Chemotherapy:
- See Disease Characteristics
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Ephraim J. Fuchs, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000068057, J9966
NCT ID:
NCT00006042
Start Date:
December 1999
Completion Date:
Related Keywords:
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Diseases
- recurrent adult Hodgkin lymphoma
- Burkitt lymphoma
- refractory multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- recurrent childhood lymphoblastic lymphoma
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- relapsing chronic myelogenous leukemia
- refractory chronic lymphocytic leukemia
- chronic phase chronic myelogenous leukemia
- adult acute myeloid leukemia in remission
- adult acute lymphoblastic leukemia in remission
- childhood acute myeloid leukemia in remission
- childhood acute lymphoblastic leukemia in remission
- recurrent/refractory childhood Hodgkin lymphoma
- stage II adult lymphoblastic lymphoma
- stage III grade 3 follicular lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III adult Burkitt lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult Burkitt lymphoma
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- recurrent childhood small noncleaved cell lymphoma
- recurrent childhood large cell lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- recurrent mantle cell lymphoma
- childhood chronic myelogenous leukemia
- atypical chronic myeloid leukemia
- myelodysplastic/myeloproliferative disease, unclassifiable
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- childhood myelodysplastic syndromes
- Neoplasms
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
