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Cytarabine, Cyclophosphamide, Alemtuzumab, and Total Body Irradiation Followed By a Donor Stem Cell Transplant and Donor T-cell Infusions in Treating Patients With Leukemia or Other Hematologic Disorders
This study has been completed.
First Received: February 22, 2008   Last Updated: July 14, 2009   History of Changes
Sponsored by: Baylor College of Medicine
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00622297
  Purpose

RATIONALE: Giving chemotherapy, a monoclonal antibody, and total body irradiation before a donor stem cell 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 certain 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 infusions of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory with immunotoxin after the transplant may keep this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells when given together with a donor stem cell transplant after chemotherapy, monoclonal antibody therapy, and total body irradiation in treating patients with leukemia or other hematologic disorders.


Condition Intervention Phase
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Precancerous/Nonmalignant Condition
Biological: RFT5-dgA immunotoxin
Biological: alemtuzumab
Biological: therapeutic allogeneic lymphocytes
Drug: cyclophosphamide
Drug: cytarabine
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label
Official Title: A PHASE I TRIAL EVALUATING THE USE OF RFT5-DGA TO DEPLETE ALLOREACTIVE CELLS PRIOR TO HAPLOIDENTICAL STEM CELL TRANSPLANTATION

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of donor lymphocytes given to patients [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immune reconstitution [ Designated as safety issue: Yes ]
  • Overall survival at 100 days and 1 year [ Designated as safety issue: No ]
  • Disease-free survival at 100 days and 1 year [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: July 2000
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • To determine the number of donor lymphocytes that can be given to recipients of haploidentical stem cell transplants after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin, and will result in a rate of grade III/IV graft-versus-host disease ≤ 25%.
  • To analyze immune reconstitution in these patients.
  • To measure their overall and disease-free survival at 100 days and at 1 year.

OUTLINE:

  • Preparative regimen: Patients receive cytarabine IV every 12 hours on days -8 to -5, cyclophosphamide IV on days -7 to -6, and alemtuzumab IV on days -3 to -1. Patients also undergo total body irradiation twice daily on days -4 to -1.
  • Stem cell infusion: Patients undergo allogeneic stem cell transplantation.
  • Allogeneic T-cell infusion: Patients undergo allogeneic T- cell transplantation.
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Confirmed diagnosis of one of the following:

    • Acute lymphoblastic leukemia meeting the following criteria:

      • Stage III or IV disease
      • Relapsed disease or primary refractory disease
    • Stage III or IV high-grade non-Hodgkin lymphoma meeting 1 of the following criteria:

      • Relapsed disease
      • Primary refractory disease
    • Myelodysplastic syndromes
    • Acute myeloid leukemia after first relapse or with primary refractory disease
    • Chronic myelogenous leukemia hemophagocytic lymphohistiocytosis
    • Familial hemophagocytic lymphohistiocytosis
    • Viral-associated hemophagocytic syndrome
    • X-linked lymphoproliferative disease with severe, chronic, active Epstein-Barr virus infection with predilection for T- or NK-cell malignancy
  • Lack of suitable conventional donor (i.e., 5/6 or 6/6 related or 5/6 or 6/6 unrelated donor) or presence of a rapidly progressive disease not permitting time to identify an unrelated donor NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

  • Life expectancy > 6 months (not limited by disease other than leukemia)
  • No symptomatic cardiac disease or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction < 25%)
  • Creatinine clearance ≥ 40 mL/min
  • No pre-existing severe restrictive pulmonary disease
  • FVC ≥ 40% of predicted
  • Direct bilirubin ≤ 3 μg/dL
  • AST ≤ 500 μg/dL
  • No severe personality disorder or mental illness that would preclude compliance with the study
  • No severe infection that would precluded ablative chemotherapy or successful transplantation
  • No HIV positivity

PRIOR CONCURRENT THERAPY:

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00622297

Locations
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Study Chair: Malcolm K. Brenner, MD, PhD Baylor College of Medicine
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000582429, BCM-H-9033
Study First Received: February 22, 2008
Last Updated: July 14, 2009
ClinicalTrials.gov Identifier: NCT00622297     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent childhood acute lymphoblastic leukemia
childhood myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
hemophagocytic lymphohistiocytosis
childhood immunoblastic large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
stage III childhood small noncleaved cell lymphoma
stage IV childhood small noncleaved cell lymphoma
Burkitt lymphoma
recurrent adult Burkitt lymphoma

Study placed in the following topic categories:
Anti-Infective Agents
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Follicular Lymphoma
Mycoses
Preleukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Alemtuzumab
Lymphoma, Large-Cell, Anaplastic
Neoplasm Metastasis
Myelodysplastic Myeloproliferative Disease
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphohistiocytosis, Hemophagocytic
Immunoproliferative Disorders
Hematologic Diseases
Myeloproliferative Disorders
Leukemia, Myeloid
Waldenstrom Macroglobulinemia
B-cell Lymphomas
Hemophagocytic Lymphohistiocytosis
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin
Antimetabolites
Acute Lymphoblastic Leukemia, Childhood
Leukemia, Lymphoid
Immunologic Factors
Precancerous Conditions
Lymphoma, Follicular

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Precancerous Conditions
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Leukemia
Preleukemia
Pathologic Processes
Therapeutic Uses
Syndrome
Alemtuzumab
Lymphoma, Large-Cell, Immunoblastic
Alkylating Agents
Lymphoma
Cytarabine
Neoplasms by Histologic Type
Immunoproliferative Disorders
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Immunotoxins

ClinicalTrials.gov processed this record on September 03, 2009