Clinical trial NCT00005852: Bone Marrow Transplantation in Treating Patients With Severe Aplastic Anemia or Rejection of Previous Bone Marrow Transplant
Official title: Allogeneic Bone Marrow Transplantation for Marrow Failure States
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
primary myelofibrosis
childhood acute promyelocytic leukemia (M3)
refractory hairy cell leukemia
recurrent/refractory childhood Hodgkin 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
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
graft versus host disease
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
childhood myelodysplastic syndromes
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-26
Sex: ALL
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Bone marrow from donors may be able to treat patients with severe aplastic anemia and patients whose bodies have rejected previous bone marrow transplantation.

PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have severe aplastic anemia or whose bodies have rejected previous bone marrow transplant.

Detailed description: OBJECTIVES: I. Determine the graft failure rate and overall survival of patients with severe aplastic anemia after receiving an allogeneic bone marrow transplant. II. Determine the efficacy of high dose cyclophosphamide and antithymocyte globulin as conditioning regimen for a second bone marrow transplant in patients who reject their first graft. III. Determine the efficacy of methylprednisolone and anti-CD3 monoclonal antibody as a conditioning regimen for a second bone marrow transplant in patients who reject their first graft and are poor candidates for cyclophosphamide and antithymocyte globulin.

OUTLINE: Patients with graft failure with the following organ function and performance status are assigned to arm I: Performance status: Karnofsky 60-100% Pulmonary: FEV1 and DLCO at least 50% Cardiac: Left ventricular ejection fraction at least 45% Hepatic: None to mild venoocclusive disease Patients with graft failure with the following organ function and performance status are assigned to arm II: Performance status: Karnofsky 20-50% Pulmonary: FEV1 or DLCO less than 50% Cardiac: Left ventricular ejection fraction less than 45% Hepatic: Moderate to severe venoocclusive disease Patients with aplastic anemia are assigned to arm I. Arm I: Patients receive cyclophosphamide IV over 1 hour on days -5 to -2, antithymocyte globulin IV over 8 hours on days -5 to -3, and bone marrow transplant on day 0. Arm II: Patients receive methylprednisolone IV twice a day on days -5 to 62; monoclonal antibody OKT3 IV on days -1 to 24; bone marrow transplant on day 0; oral cyclosporine twice a day starting day 20; and filgrastim (G-CSF) subcutaneously once a day starting day -5 until blood counts recover. Patients are followed once a week for 3 months and then monthly for one year.

PROJECTED ACCRUAL: A total of 40 patients (20 with aplastic anemia and 20 with graft failure) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed aplastic anemia Must have related donor with a genotypic 6 out of 6 HLA A, B, and DR match OR Bone marrow transplant failure Must have related donor with at least a 5 out of 6 HLA match OR Must have an unrelated donor with at least a 5 out of 6 HLA match

PATIENT CHARACTERISTICS: Age: 15 to 55 Performance status: Aplastic anemia patients: Karnofsky 80-100% Graft failure patients: Karnofsky 20-100% Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Aplastic anemia patients: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 3 times normal PT/PTT normal (except when aplastic anemia secondary to viral hepatitis) Graft failure patients: Mild to severe venoocclusive disease allowed Renal: Aplastic anemia patients: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: Aplastic anemia patients: Left ventricular ejection fraction at least 45% by MUGA or echocardiography No myocardial infarction within the past 6 months No uncontrolled arrhythmias Pulmonary: Aplastic anemia patients: FEV1 and DLCO at least 50% predicted Other: Aplastic anemia patients: No uncontrolled diabetes mellitus or thyroid disease No active serious infections HIV negative Not pregnant or nursing Negative pregnancy test No psychosocial problem that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Steven C. Goldstein, MD
role: STUDY_CHAIR
References: