Total-Body Irradiation and Chemotherapy Followed By Donor Bone Marrow Transplant in Treating Young Patients With Hematologic Cancer

NCT00028730 | Completed Phase 2

• 6 other identifiers: 01-105P30CA008748P01CA033049P01CA023766MSKCC-01105NCI-H01-0083
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening. PURPOSE: This phase II trial is studying how well total-body irradiation and chemotherapy followed by T-cell depleted donor bone marrow transplant works in treating young patients with hematologic cancer.

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Keywords

recurrent childhood lymphoblastic lymphoma; chronic phase chronic myelogenous leukemia; childhood acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; myelodysplastic/myeloproliferative neoplasm, unclassifiable

Outcome Measures

Primary Outcomes (2)

• Minimal transplantation related mortality

  2 years

• High disease-free survival at 2 years

  2 years

Study Arms (1)

Pts < than or = 18 years with lymphohematopoietic disorders

EXPERIMENTAL

This is a phase II, single-center study to evaluate a cytoreductive regimen of hyperfractionated TBI, thiotepa and cyclophosphamide (HFTBI/thio/cy) followed by infusions of SBA-E- T-cell depleted marrow in pediatric leukemia recipients of either HLA-identical or HLA-1Ag non-identical related or unrelated donors.

Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: thiotepa; Procedure: allogeneic bone marrow transplantation; Radiation: radiation therapy

Interventions

anti-thymocyte globulin BIOLOGICAL

Pts < than or = 18 years with lymphohematopoietic disorders

filgrastim BIOLOGICAL

Pts < than or = 18 years with lymphohematopoietic disorders

cyclophosphamide DRUG

Pts < than or = 18 years with lymphohematopoietic disorders

fludarabine phosphate DRUG

Pts < than or = 18 years with lymphohematopoietic disorders

thiotepa DRUG

Pts < than or = 18 years with lymphohematopoietic disorders

allogeneic bone marrow transplantation PROCEDURE

Pts < than or = 18 years with lymphohematopoietic disorders

radiation therapy RADIATION

Pts < than or = 18 years with lymphohematopoietic disorders

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * One of the following diagnoses: * Histologically confirmed good-risk acute myeloid leukemia (AML) in first remission with an HLA-compatible related donor * Ineligible for unrelated bone marrow transplantation unless failed first-line induction chemotherapy or have molecular evidence of disease at time of transplantation * Histologically confirmed high-risk AML in first remission * High risk defined by cytogenetics, biphenotypic and undifferentiated leukemia phenotype, secondary AML, or AML after myelodysplastic syndromes (MDS) * Eligible for related or unrelated donor transplantation * Histologically confirmed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) in first remission with high risk for relapse or in second or third remission * High risk for relapse defined by hypodiploidy, pseudodiploidy with translocations t(9;22) or infant t(4;11), or failure to achieve remission after four weeks of induction therapy * Eligible for related or unrelated donor transplantation * Histologically confirmed chronic myelogenous leukemia (CML) in at least first chronic phase or acceleration with an HLA-compatible related donor * Histologically confirmed CML in first chronic phase if failed conventional therapy or in at least second chronic phase or acceleration with an HLA-compatible unrelated donor * Histologically confirmed non-Hodgkin's lymphoma beyond first complete remission or primary induction failure and tumors that are chemosensitive defined as at least 50% reduction in mass size * Eligible for related or unrelated donor transplantation * Histologically confirmed MDS with intermediate or high-risk disease defined by International Prognostic Scoring System and paroxysmal nocturnal hematuria * Eligible for related or unrelated donor transplantation * Treatment-related MDS or leukemia allowed if primary malignancy (e.g., neuroblastoma or Ewing's sarcoma) at low risk of recurrence * No AML, ALL, or LL in relapse or greater than third remission * No CML in blast crisis defined as more than 30% blasts plus promyelocytes * No active CNS involvement * History of leukemia cutis allowed * HLA compatible donor available * 5/6 or 6/6 HLA antigen matched related or unrelated PATIENT CHARACTERISTICS: Age: * 18 and under Performance status: * Karnofsky 70-100% OR * Lansky 50-100% Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * Bilirubin no greater than 2.5 times upper limit of normal (ULN) * AST no greater than 3 times ULN (unless liver involvement is present) Renal: * Creatinine normal OR * Creatinine clearance greater than 60 mL/min Cardiovascular: * LVEF at least 50% at rest (if less than 50% at rest, must increase with exercise) Pulmonary: * Asymptomatic with no prior risk features OR * DLCO greater than 40% predicted (corrected for hemoglobin) if symptomatic Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV I/II negative * No uncontrolled viral, bacterial, or fungal infection * No known hypersensitivity to bovine proteins PRIOR CONCURRENT THERAPY: Biologic therapy: * See Disease Characterisitics Chemotherapy: * See Disease Characteristics Endocrine therapy: * Not specified Radiotherapy: * No prior radiotherapy that would preclude total body irradiation dose Surgery: * Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Chronic-Phase; Burkitt Lymphoma; Dendritic Cell Sarcoma, Interdigitating; Myeloproliferative Disorders

Interventions

Antilymphocyte Serum; Filgrastim; Cyclophosphamide; fludarabine phosphate; Thiotepa; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Histiocytic Disorders, Malignant; Histiocytosis

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Nancy A. Kernan, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2002
• First Posted: January 27, 2003
• Study Start: August 1, 2001
• Primary Completion: July 1, 2006
• Study Completion: June 1, 2008
• Last Updated: December 22, 2015

Record last verified: 2015-12

Locations

US (1)