Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Biological: anti-thymocyte globulin Biological: filgrastim Drug: cyclophosphamide Drug: fludarabine phosphate Drug: thiotepa Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : August 2001
Actual Primary Completion Date : July 2006
Actual Study Completion Date : June 2008

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Minimal transplantation related mortality [ Time Frame: 2 years ]
  2. High disease-free survival at 2 years [ Time Frame: 2 years ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00028730


Locations
Layout table for location information
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Nancy A. Kernan, MD Memorial Sloan Kettering Cancer Center
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00028730    
Other Study ID Numbers: 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
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: December 22, 2015
Last Verified: December 2015
Keywords provided by Memorial Sloan Kettering Cancer Center:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Preleukemia
Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
 Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cyclophosphamide
Thiotepa
Fludarabine
Fludarabine phosphate
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action