- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00028730
Total-Body Irradiation and Chemotherapy Followed By Donor Bone Marrow Transplant in Treating Young Patients With Hematologic Cancer
Phase II Trial of T-Cell Depleted Hematopoietic Stem Cell Transplants (SBA-E-BM) From HLA Compatible Related or Unrelated Donors After a Myeloablative Preparative Regimen of Hyperfractionated TBI, Thiotepa and Cyclophosphamide (TBI/Thio/cy) for Treatment of Patients Less Than or Equal to 18 Years With Lymphohematopoietic Disorders
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.
Study Overview
Status
Detailed Description
OBJECTIVES:
- Determine the efficacy of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide followed by T-cell-depleted allogeneic bone marrow transplantation in children with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, or myelodysplastic syndromes.
- Correlate the progenitor cell dose and dose of clonable T cells with the incidence and quality of engraftment, extent of chimerism, incidence and severity of acute and chronic graft-versus-host disease, characteristics of hematopoietic and immunologic reconstitution, and overall and disease-free survival at 2 years in patients treated with this regimen.
OUTLINE: Patients undergo total body irradiation three times daily on days -9 to -7 and twice on day -6. Patients receive thiotepa IV over 4 hours on days -5 and -4 and cyclophosphamide IV over 30 minutes on days -3 and -2. Patients who cannot receive cyclophosphamide, due to prior hemorrhagic cystitis or exposure to high-dose cyclophosphamide or ifosfamide, receive fludarabine IV over 30 minutes on days -5 to -1. Patients planning to receive family member HLA-mismatched or unrelated bone marrow transplantation receive horse anti-thymocyte globulin IV once daily on days -5 and -4. Patients undergo allogeneic T-cell-depleted bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) IV every 12 hours beginning on day 7 and continuing until blood counts recover.
Patients are followed every 2-4 weeks for the first 100 days post-transplantation, every 6 weeks for 6 months, every 3 months for 1 year, and then every 3-6 months until 2 years post-transplantation.
PROJECTED ACCRUAL: A total of 50 patients (25 with HLA 6/6 antigen-matched related donors and 25 with HLA 5/6 antigen-matched related donors or HLA 5/6 or 6/6 antigen-matched unrelated donors) will be accrued for this study within 3 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pts < than or = 18 years with lymphohematopoietic disorders
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Minimal transplantation related mortality
Time Frame: 2 years
|
2 years
|
High disease-free survival at 2 years
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Nancy A. Kernan, MD, Memorial Sloan Kettering Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- recurrent childhood small noncleaved cell lymphoma
- recurrent childhood large cell lymphoma
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- secondary acute myeloid leukemia
- childhood acute lymphoblastic leukemia in remission
- childhood acute myeloid leukemia in remission
- chronic phase chronic myelogenous leukemia
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- recurrent childhood lymphoblastic lymphoma
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Lymphoma
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Fludarabine
- Fludarabine phosphate
- Thiotepa
- Antilymphocyte Serum
Other Study ID Numbers
- 01-105
- P30CA008748 (U.S. NIH Grant/Contract)
- P01CA023766 (U.S. NIH Grant/Contract)
- P01CA033049 (U.S. NIH Grant/Contract)
- MSKCC-01105
- NCI-H01-0083
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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