Status:

COMPLETED

Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

Lead Sponsor:

UNC Lineberger Comprehensive Cancer Center

Collaborating Sponsors:

National Cancer Institute (NCI)

Conditions:

Chronic Myeloproliferative Disorders

Leukemia

Eligibility:

All Genders

10+ years

Phase:

PHASE2

Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as busulfan and fludarabine, before a donor stem cell transplant helps stop the growth of cancer and abnormal cells. It also helps stop the patient's ...

Detailed Description

OBJECTIVES: Primary * Determine the clinical efficacy and toxicity profiles of a nonmyeloablative preparative regimen comprising busulfan and fludarabine with or without anti-thymocyte globulin foll...

Eligibility Criteria

Inclusion

  • DISEASE CHARACTERISTICS:
  • Histologically confirmed diagnosis of 1 of the following:
  • Chronic lymphocytic leukemia (CLL), meeting the following criteria:
  • Absolute lymphocyte count \> 5,000/mm³
  • Lymphocytes must appear morphologically mature with \< 55% prolymphocytes
  • Lymphocyte phenotype with expression of CD19 and cluster of differentiation 5 (CD5)
  • Prolymphocytic leukemia (PLL), meeting the following criteria:
  • Absolute lymphocyte count \> 5,000/mm³
  • More than 55% prolymphocytes
  • Morphologically diagnosed
  • Chronic myelogenous leukemia (CML), meeting the following criteria:
  • Diagnosis of CML or similar myeloproliferative disorders based on t(9;22) or related t(9;12) cytogenetic abnormalities AND characterized by elevated white blood cell (WBC) counts in peripheral blood or bone marrow
  • In first chronic phase CML and a candidate for treatment with reduced-dose busulfan
  • Patients with other cytogenetic abnormalities, such as t(9;12), that are associated with an aggressive clinical course are eligible
  • Non-Hodgkin's lymphoma (NHL), meeting the following criteria:
  • Any World Health Organization (WHO) class histologic subtype allowed
  • Core biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping
  • Bone marrow biopsies as sole means of diagnosis are not allowed for follicular lymphoma
  • Hodgkin's lymphoma, meeting the following criteria:
  • Any WHO class histologic subtype allowed
  • Core biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping
  • Multiple myeloma, meeting the following criteria:
  • Active disease requiring treatment (Durie-Salmon stages I, II, or III)
  • Acute myeloid leukemia with documented control, defined as \< 10% bone marrow blasts and no circulating blasts
  • Acute lymphoblastic leukemia, meeting the following criteria:
  • In early first relapse or beyond OR in first complete remission and has 1 of the following high-risk features:
  • t(9;22) or t(4;11)
  • WBC count \> 30,000/mm³ at presentation
  • Non-T-cell phenotype
  • More than 30 years of age
  • Agnogenic myeloid metaplasia/myelofibrosis
  • Patients who are transfusion dependent or who have evolving myelodysplastic or leukemic features or high-risk cytogenetic abnormalities are eligible
  • Myelodysplastic syndromes (MDS) as defined by WHO criteria
  • Meets 1 of the following criteria:
  • Over 55 years of age
  • Ineligible for busulfan-based therapy based on diminished organ function or poor performance status
  • Indolent and chemotherapy-responsive CLL, low-grade NHL, small lymphocytic lymphoma, or PLL
  • Patients who have undergone prior autologous stem cell transplantation are preferentially enrolled on clinical trial CALGB-100002, if available and patient is eligible
  • HLA-matched or mismatched related donor or HLA-matched unrelated donor available
  • HLA-identical sibling (6/6 or 9/10) (minimal serologic typing required for class I \[A, B\]; molecular typing required for class II (DRB1))
  • 9/10 matched unrelated donor (MUD) (molecular analysis at HLA A, B, C, DRB1, and DQB1 by high resolution typing required)
  • 5/6 MUD (molecular analysis at HLA A, B, and DRB1 required)
  • No syngeneic donors
  • PATIENT CHARACTERISTICS:
  • Creatinine clearance ≥ 40 mL/min
  • Bilirubin ≤ 3 times upper limit of normal (ULN)
  • aspartate aminotransferase (AST) ≤ 3 times ULN
  • Diffusing capacity of the lungs for carbon monoxide (DLCO) \> 40% with no symptomatic pulmonary disease
  • Left ventricular ejection fraction (LVEF) ≥ 30% by multigated acquisition scan (MUGA)
  • No uncontrolled diabetes mellitus or active serious infection
  • No known hypersensitivity to Escherichia coli-derived products
  • No HIV infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • PRIOR CONCURRENT THERAPY:
  • See Disease Characteristics
  • More than 4 weeks since prior chemotherapy, radiotherapy (except prophylactic cranial x-ray therapy), or surgery

Exclusion

    Key Trial Info

    Start Date :

    January 7 2011

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    May 23 2012

    Estimated Enrollment :

    71 Patients enrolled

    Trial Details

    Trial ID

    NCT00448201

    Start Date

    January 7 2011

    End Date

    May 23 2012

    Last Update

    May 30 2017

    Active Locations (1)

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    1

    Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, United States, 27599-7295