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

Primary Purpose

Leukemia, Lymphoma, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
filgrastim
cyclophosphamide
fludarabine phosphate
thiotepa
allogeneic bone marrow transplantation
radiation therapy
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pts < than or = 18 years with lymphohematopoietic disorders

Arm Description

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.

Outcomes

Primary Outcome Measures

Minimal transplantation related mortality
High disease-free survival at 2 years

Secondary Outcome Measures

Full Information

First Posted
January 4, 2002
Last Updated
December 21, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00028730
Brief Title
Total-Body Irradiation and Chemotherapy Followed By Donor Bone Marrow Transplant in Treating Young Patients With Hematologic Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
August 2001 (undefined)
Primary Completion Date
July 2006 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pts < than or = 18 years with lymphohematopoietic disorders
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
thiotepa
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Minimal transplantation related mortality
Time Frame
2 years
Title
High disease-free survival at 2 years
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy A. Kernan, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

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

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