Allogeneic Blood or Marrow Transplantation for Hematologic Malignancy and Aplastic Anemia
busulfan
+ cyclophosphamide
+ anti-thymocyte globulin
Lymphadenopathy+85
+ Bone Marrow Failure Disorders
+ Anemia
Treatment Study
Summary
Study start date: October 19, 1998
Actual date on which the first participant was enrolled.OBJECTIVES: Compare the morbidity, mortality, and overall outcome of patients with severe aplastic anemia or hematologic malignancy treated with standard vs novel conditioning regimens followed by allogeneic stem cell transplantation. Examine the influence of donor histocompatibility on outcome by comparing matched/related, mismatched/related (with or without T-cell depletion), and matched/unrelated transplants with stratification for type of preparative regimen. Ensure that patients with uncommon diagnoses will be treated in a uniform fashion with the best therapy available. OUTLINE: Patients are stratified according to risk of relapse (standard-risk: acute leukemia in first complete remission, chronic myelogenous leukemia in first chronic phase, lymphoma in sensitive first relapse or second remission, primary or untreated myelodysplastic syndromes, or untreated severe aplastic anemia vs high-risk: all others). Patients are assigned to one of the following conditioning regimens based on diagnosis, risk of relapse, and donor relatedness: Regimen 1: 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. Regimen 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. Regimen 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. Regimen 4: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 1 hour on days -3 and -2. Regimen 5: 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. Regimen 6: Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. Regimen 7: 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. Regimen 8: 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. Regimen 9: 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. All patients then receive donor stem cell infusions on day 0. Some patients may undergo involved-field radiotherapy 4-8 weeks after transplant. Patients will be taken off study after a minimum of 4 years of follow up. PROJECTED ACCRUAL: At least 405 patients will be accrued for this study within 5 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.361 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 4 to 70 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.9 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalGroup III
ExperimentalGroup IV
ExperimentalGroup 5
ExperimentalGroup 6
ExperimentalGroup 7
ExperimentalGroup 8
ExperimentalGroup 9
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Roswell Park Cancer Institute
Buffalo, United StatesOpen Roswell Park Cancer Institute in Google Maps