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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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ClinicalTrials.gov Identifier: NCT00028730
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : December 22, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE January 4, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date December 22, 2015
Study Start Date  ICMJE August 2001
Actual Primary Completion Date July 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
  • Minimal transplantation related mortality [ Time Frame: 2 years ]
  • High disease-free survival at 2 years [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Total-Body Irradiation and Chemotherapy Followed By Donor Bone Marrow Transplant in Treating Young Patients With Hematologic Cancer
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
Intervention  ICMJE
  • Biological: anti-thymocyte globulin
  • Biological: filgrastim
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Drug: thiotepa
  • Procedure: allogeneic bone marrow transplantation
  • Radiation: radiation therapy
Study Arms  ICMJE 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.
Interventions:
  • Biological: anti-thymocyte globulin
  • Biological: filgrastim
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Drug: thiotepa
  • Procedure: allogeneic bone marrow transplantation
  • Radiation: radiation therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 18, 2014)
25
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2008
Actual Primary Completion Date July 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00028730
Other Study ID Numbers  ICMJE 01-105
P30CA008748 ( U.S. NIH Grant/Contract )
P01CA033049 ( U.S. NIH Grant/Contract )
P01CA023766 ( U.S. NIH Grant/Contract )
MSKCC-01105
NCI-H01-0083
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Nancy A. Kernan, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP