Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

Completed · Not applicable

Conditions studied: Accelerated Phase Chronic Myelogenous Leukemia, Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), 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 Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Aplastic Anemia, Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, Childhood Myelodysplastic Syndromes, Childhood Nasal Type Extranodal NK/T-cell Lymphoma, Chronic Eosinophilic Leukemia, Chronic Myelomonocytic Leukemia, Chronic Neutrophilic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Fanconi Anemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Burkitt Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Paroxysmal Nocturnal Hemoglobinuria, Previously Treated Myelodysplastic Syndromes, Primary Myelofibrosis, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Anaplastic Large Cell Lymphoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Splenic Marginal Zone Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma, Waldenström Macroglobulinemia

In brief

This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell transplant works in treating patients with hematologic cancer or bone marrow failure disorders. Giving low doses of chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect)

Key facts

Study ID

NCT00856388

Run by

Roswell Park Cancer Institute

People needed

62

Starts

2009-01-14

Expected to finish

2019-03-13

Last updated by the study team

2019-11-13

Who can join

Age: 3 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Diagnosis of a histology documented hematologic malignancy or marrow disorder
• Bone marrow failure disorders and other non-malignant hematologic or immunologic disorders:
• Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH):
• Primary allogeneic hematopoietic stem cell transplantation (HSCT) is appropriate for selected patients with severe aplastic anemia; however, patients with aplastic anemia must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully-matched donor is not available
• Patients with PNH must have a history of thrombosis related to PNH
• Hereditary bone marrow failure disorders include Fanconi anemia or related chromosomal breakage syndrome dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, congenital amegakaryocytic thrombocytopenia:
• Fanconi anemia or related chromosomal breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable
• Dyskeratosis: diagnosis is supported by using either telomerase reverse transcriptase (TERC) gene mutation in autosomal dominant Dyskeratosis Congenita or Xlinked DKC1 gene mutation
• Other non-malignant hematologic or immunologic disorders that require transplantation
• Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia)
• Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)
• Congenital primary immunodeficiencies (including but not limited to Severe Combined Immunodeficiency Syndrome, Wiskott-Aldrick syndrome, CD40 ligand deficiency, T-cell deficiencies)
• Acute leukemias:
• Subjects must be ineligible for conventional myeloablative transplantation;
• Resistant or recurrent disease after at least one standard combination chemotherapy regime or first remission patients at high risk of relapse OR First remission patients at high risk of relapse:
• Acute myeloid leukemia (AML)- antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular features (e.g. Flt3-ITD mutation, mixed-lineage leukemia [MLL], wildtype NPM1);
• Acute lymphocytic leukemia (ALL)- high or standard risk ALL
• Chronic Myeloid Leukemia (CML):
• Chronic phase (intolerant or unresponsive to imatinib and/or other tyrosine kinase inhibitors), second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation
• Myeloproliferative and myelodysplastic syndromes (MDS):
• Myelofibrosis (with/without splenectomy) with intermediate to high risk features
• Advanced polycythemia vera not responding to standard therapy
• MDS with an international prostate symptom score (IPSS) score of Int-2 or higher
• MDS with lower IPSS scores Int-1 or less with severe clinical features such as severe neutropenia or thrombocytopenia or high risk chromosome abnormalities such as monosomy 7
• Secondary massively parallel signature sequencing (MPSS) with any IPSS scores

You may not qualify if…

• Uncontrolled central nervous system (CNS) disease (for hematologic malignancies)
• Karnofsky (adult) or Lansky (for =< 16 years) performance status =< 50%
• Diffusing capacity of the lung for carbon monoxide (DLCO) less than 40% predicted, corrected for hemoglobin (Hb) and/or alveolar ventilation
• Cardiac: left ventricular ejection fraction less than 40%
• Bilirubin >= 3 x upper limit of normal
• Liver alkaline phosphatase >= 3 x upper limit of normal
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvate transaminase (SGPT) >= 3 x upper limit of normal
• Child's class B and C liver failure
• Calculated creatinine clearance < 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics
• Patients who have received maximally allowed doses (given in 2 Gy fractions, or equivalent) of previous radiation therapy to various organs as follows:
• Mediastinum 40 Gy
• Heart (any volume) 36 Gy
• Whole lungs 12 Gy
• Small bowel (any volume) 46 Gy
• Kidneys 12 Gy
• Whole liver 20 Gy
• Spinal cord (any volume) 36 Gy
• Whole brain 30 Gy Enrollment of patients who previously receive higher than allowed dose of radiation to a small volume of lungs, liver, and brain will be determine by the discretion of the radiation oncologist on the study
• Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
• Human immunodeficiency virus (HIV) positive
• Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening
• Females of childbearing potential with a positive pregnancy test

Where it is running

• Roswell Park Cancer Institute — Buffalo, New York, United States

Full record on ClinicalTrials.gov

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