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 (LCCC 0306)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00448201
First received: March 14, 2007
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

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 immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Immunosuppressive therapy may improve bone marrow function and may be an effective treatment for hematologic cancer or other disease.

PURPOSE: This clinical trial is studying the side effects and how well giving busulfan and fludarabine with or without antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer or other disease.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Biological: anti-thymocyte globulin
Biological: sargramostim
Biological: therapeutic allogeneic lymphocytes
Drug: busulfan
Drug: fludarabine phosphate
Drug: methotrexate
Drug: tacrolimus
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Disorders Who Are Ineligible or Inappropriate for Treatment With a More Intensive Therapeutic Regimen

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphoma, Small Cleaved-cell, Diffuse Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Multiple Myeloma Chronic Myeloproliferative Disorders Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Myelofibrosis Burkitt Lymphoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia, Childhood Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Mycosis Fungoides Sezary Syndrome Anaplastic Plasmacytoma
U.S. FDA Resources

Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Treatment-related mortality [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response at 6 and 12 months post-transplant [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Complete or mixed donor chimerism at 30, 60, and 90 days post-transplant [ Time Frame: Days 30, 60, and 90 ] [ Designated as safety issue: No ]
  • 5-year disease-free survival [ Time Frame: Year 5 ] [ Designated as safety issue: No ]
  • Graft-vs-host disease at 6 months post-transplant [ Time Frame: 6 Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: November 2003
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Methotrexate Only Arm
GVHD Prophylaxis with Methotrexate
Biological: sargramostim
GM-CSF 500 ug QD subcutaneously will be given to recipients who remain with an ANC < 1000/uL past day 20
Biological: therapeutic allogeneic lymphocytes
A minimum total CD34+ cell dose of 3 x 10^6 cells/kg and a maximum 8 x 10^6 cells/kg will be infused on day 0
Drug: busulfan
6.4 mg/kg by continuous IV infusion over 48 hours on Days -6 and -5
Drug: fludarabine phosphate
fludarabine 30 mg/m^2/day x 5 days IVPB over 30 minutes on Days -7 through -3
Drug: methotrexate
Methotrexate 5 mg/m^2 per day on days +1, +3 and +6
Drug: tacrolimus
Suggested starting dose is 0.03 mg/kg po bid starting on Day -1
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0
Procedure: peripheral blood stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0
Active Comparator: 2 Doses ATG + Methotrexate
GVHD prophylaxis with ATG + Methotrexate
Biological: anti-thymocyte globulin
0.5 mg/kg on day -3, 2.5 mg/kg on day -2 (groups 2, 3 and 4) and 3 mg/kg on day -1 (group 4 only)
Biological: sargramostim
GM-CSF 500 ug QD subcutaneously will be given to recipients who remain with an ANC < 1000/uL past day 20
Biological: therapeutic allogeneic lymphocytes
A minimum total CD34+ cell dose of 3 x 10^6 cells/kg and a maximum 8 x 10^6 cells/kg will be infused on day 0
Drug: busulfan
6.4 mg/kg by continuous IV infusion over 48 hours on Days -6 and -5
Drug: fludarabine phosphate
fludarabine 30 mg/m^2/day x 5 days IVPB over 30 minutes on Days -7 through -3
Drug: methotrexate
Methotrexate 5 mg/m^2 per day on days +1, +3 and +6
Drug: tacrolimus
Suggested starting dose is 0.03 mg/kg po bid starting on Day -1
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0
Procedure: peripheral blood stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0
Active Comparator: 2 Doses ATG
GVHD prophylaxis with 2 doses ATG
Biological: anti-thymocyte globulin
0.5 mg/kg on day -3, 2.5 mg/kg on day -2 (groups 2, 3 and 4) and 3 mg/kg on day -1 (group 4 only)
Biological: sargramostim
GM-CSF 500 ug QD subcutaneously will be given to recipients who remain with an ANC < 1000/uL past day 20
Biological: therapeutic allogeneic lymphocytes
A minimum total CD34+ cell dose of 3 x 10^6 cells/kg and a maximum 8 x 10^6 cells/kg will be infused on day 0
Drug: busulfan
6.4 mg/kg by continuous IV infusion over 48 hours on Days -6 and -5
Drug: fludarabine phosphate
fludarabine 30 mg/m^2/day x 5 days IVPB over 30 minutes on Days -7 through -3
Drug: tacrolimus
Suggested starting dose is 0.03 mg/kg po bid starting on Day -1
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0
Procedure: peripheral blood stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0
Active Comparator: 3 Doses ATG
GVHD prophylaxis with 3 doses ATG
Biological: anti-thymocyte globulin
0.5 mg/kg on day -3, 2.5 mg/kg on day -2 (groups 2, 3 and 4) and 3 mg/kg on day -1 (group 4 only)
Biological: sargramostim
GM-CSF 500 ug QD subcutaneously will be given to recipients who remain with an ANC < 1000/uL past day 20
Biological: therapeutic allogeneic lymphocytes
A minimum total CD34+ cell dose of 3 x 10^6 cells/kg and a maximum 8 x 10^6 cells/kg will be infused on day 0
Drug: busulfan
6.4 mg/kg by continuous IV infusion over 48 hours on Days -6 and -5
Drug: fludarabine phosphate
fludarabine 30 mg/m^2/day x 5 days IVPB over 30 minutes on Days -7 through -3
Drug: tacrolimus
Suggested starting dose is 0.03 mg/kg po bid starting on Day -1
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0
Procedure: peripheral blood stem cell transplantation
Minimum total CD34+ cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on Day 0

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 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 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)
  • AST ≤ 3 times ULN
  • DLCO > 40% with no symptomatic pulmonary disease
  • LVEF ≥ 30% by 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00448201

Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Thomas C. Shea, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00448201     History of Changes
Other Study ID Numbers: LCCC 0306, P30CA016086, UNC-LCCC-0306, CDR0000549851
Study First Received: March 14, 2007
Last Updated: February 14, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
United States: Federal Government

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
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)
prolymphocytic leukemia
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
blastic phase chronic myelogenous leukemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:
Neoplasms
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Methotrexate
Fludarabine monophosphate
Tacrolimus

ClinicalTrials.gov processed this record on April 15, 2014