Combination Chemotherapy and Donor Stem Cell Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
About this trial
This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring recurrent childhood acute lymphoblastic leukemia, recurrent cutaneous T-cell non-Hodgkin lymphoma, Burkitt lymphoma, Waldenstrom macroglobulinemia, 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, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic 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, polycythemia vera, essential thrombocythemia, refractory anemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, T-cell large granular lymphocyte leukemia, acute undifferentiated leukemia, 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, recurrent adult T-cell leukemia/lymphoma, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, prolymphocytic leukemia, intraocular lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent mantle cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, recurrent mycosis fungoides/Sezary syndrome, primary myelofibrosis, childhood chronic myelogenous leukemia, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, 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, 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, aplastic anemia, unspecified adult solid tumor, protocol specific, unspecified childhood solid tumor, protocol specific
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of one of the following: Severe aplastic anemia as defined by either of the following: Marrow cellularity (< 25% [or 25-50% cellularity with < 30% of remaining cells hematopoietic in origin]) At least 2 of the following abnormal peripheral blood counts: Reticulocyte count < 1% (corrected for hematocrit) Platelet count < 20,000/mm^3 Neutrophil count < 500/mm^3 Histologically confirmed hematologic malignancy, including any of the following: Acute leukemia Resistant or recurrent disease after combination chemotherapy with at least one standard regimen OR in first remission and at high risk of relapse Acute myeloid leukemia (AML) (antecedent myelodysplastic syndromes [MDS], secondary AML, or high-risk cytogenetic abnormalities) Acute lymphoblastic leukemia (ALL) (high-risk cytogenetic abnormalities) Chronic myeloid leukemia (CML) Chronic phase, accelerated phase, or blast phase Myeloproliferative disorders or MDS, including any of the following: Myelofibrosis Polycythemia vera* Essential thrombocythemia* Refractory anemia Refractory anemia with excess blasts Refractory anemia with excess blasts in transformation Chronic myelomonocytic leukemia NOTE: * Only if transformed to AML or MDS Lymphoproliferative disease Recurrent or persistent, symptomatic disease after first-line chemotherapy, including any of the following: Chronic lymphocytic leukemia (CLL) (≥ 20% marrow involvement) Waldenstrom macroglobulinemia Low-grade non-Hodgkin lymphoma Intermediate or high-grade non-Hodgkin lymphoma, meeting 1 of the following criteria: Resistant or recurrent disease after combination chemotherapy with one standard regimen Lymphoblastic lymphoma or small noncleaved cell lymphoma in first remission and at high risk of relapse CNS disease Bone marrow disease and LDH greater than 300 Solid tumor that would otherwise be treated on RPCI-DS-9115 (or equivalent autologous stem transplant protocol) AND has a syngeneic donor Autologous bone marrow transplant not possible (or desirable) due to 1 of the following: History of marrow tumor Inadequate marrow dose Abnormal marrow histology or function prior to storage Thrombocytopenia or leukopenia Marrow cellularity < 20% Histocompatible donor identified Well-matched donor, as defined by 1 of the following: Family member matched for 5 or 6 HLA specificities (A, B, DR)* Unrelated donor meeting compatibility criteria of the National Marrow Donor Program (matched for HLA A, B, and DRB1 antigens)* Identical twin sibling If a compatible cord blood donor is identified and there is no suitable unrelated donor available, patient may receive cord blood transplant NOTE: *Patients ≤ 25 years of age may be singly mismatched at the A or B loci NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age: 4 to 70 Performance status: Zubrod 0-2 OR Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin < 3 times normal (unless due to disease) Alkaline phosphatase < 3 times normal (unless due to disease) SGOT < 3 times normal (unless due to disease) Hepatitis B surface antigen negative No severe hepatic disease that would preclude study participation Renal: Creatinine normal Creatinine clearance ≥ 50 mL/min No severe renal disease that would preclude study participation Cardiovascular: Cardiac ventricular ejection fraction ≥ 50% by MUGA or echocardiogram No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction, congestive heart failure, symptomatic angina, life threatening arrhythmia, or hypertension within the past 6 months) Pulmonary: DLCO or DLVA ≥ 50% predicted (corrected for hemoglobin or alveolar ventilation) Other: No serious concurrent medical or psychiatric illness No other serious organ dysfunction (unless due to underlying disease), including the following: Uncontrolled bacterial, viral, or fungal infection Uncontrolled peptic ulcer disease Uncontrolled diabetes mellitus HIV negative Cytomegalovirus status known Not pregnant PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Pretransplant cytoreductive chemotherapy allowed for patients with relapsed or refractory disease Endocrine therapy: Not specified Radiotherapy: Not eligible for total-body irradiation if prior radiotherapy exceeded the following limits: Mediastinum: 3,600 cGy Heart: 3,600 cGy Whole lungs: 1,200 cGy Small bowel: 3,600 cGy Kidneys: 1,200 cGy Whole liver: 1,600 cGy Cranial spinal: 3,600 cGy Brain: 4,000 cGy Retina: 4,000 cGy Surgery: Not specified
Sites / Locations
- Roswell Park Cancer Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Regimen 1
Regimen 2
Regimen 3
Regimen 4
Regimen 5
Regimen 6
Regimen 7
Regimen 8
Regimen 9
Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.
Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and total-body irradiation (TBI) twice daily on days -3 to -1.
Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2.
Patients receive etoposide IV over 26 hours beginning on day -5, cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.
Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.
Patients receive fludarabine IV over 30 minutes on days -5 to -1 and anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.
Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.