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Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: UCSF Helen Diller Family Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00301951
  Purpose

RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant helps stop both the growth of cancer cells and 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 chemotherapy, such as fludarabine and busulfan, and antithymocyte globulin before transplant and tacrolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving low-dose fludarabine and busulfan together with anti-thymocyte globulin, followed by donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.


Condition Intervention
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Drug: anti-thymocyte globulin
Drug: busulfan
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Drug: sargramostim
Drug: tacrolimus
Procedure: umbilical cord blood transplantation

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma
Drug Information available for: Fludarabine Fludarabine monophosphate Tacrolimus Sargramostim Granulocyte-macrophage colony-stimulating factor Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Tacrolimus anhydrous Busulfan
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies

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

Estimated Enrollment: 10
Study Start Date: December 2005
Detailed Description:

OBJECTIVES:

Primary

  • Assess the feasibility of performing umbilical cord blood transplants in older patients or younger infirm patients with advanced hematologic malignancies using a reduced-intensity preparative regimen, as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100.

Secondary

  • Describe the time to neutrophil and platelet recovery in patients treated with this regimen.
  • Determine disease-specific, event-free, and overall survival rate at days 180 and 360.
  • Determine the incidence, severity, and timing of acute and chronic graft-versus-host disease in patients treated with this regimen.
  • Evaluate T-cell, B-cell, and natural killer cell recovery in patients treated with this regimen.
  • Assess lineage-specific chimerism after transplantation and describe the contribution of each individual cord blood unit to post-transplantation hematopoiesis.

OUTLINE: This is a pilot study.

  • Reduced-intensity preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, busulfan IV over 2 hours 4 times daily on days -4 and -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1.
  • Allogeneic umbilical cord blood transplantation: Patients undergo allogeneic umbilical cord blood transplant on day 0. Patients receive sargramostim (GM-CSF) subcutaneously or IV beginning on day 7 and continuing until blood counts recover.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally (as tolerated) beginning on day -2 and continuing for approximately 9 months. Patients also receive oral mycophenolate mofetil twice daily on days 1-50.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following advanced hematologic malignancies:

    • Acute myeloid leukemia (AML) meeting the following criteria:

      • Considered incurable with chemotherapy
      • Marrow blasts ≤ 10% (may be achieved using standard chemotherapy regimen)
      • Meets any of the following criteria:

        • High-risk cytogenetics (-7, -7q, -5, -5q, t(6,9), t(9,11), complex [≥ 3 abnormalities], Philadelphia chromosome positive [Ph+])
        • AML evolved from prior myelodysplasia
        • AML secondary to prior chemotherapy
        • Failed to achieve remission
        • In second or subsequent remission
        • Refractory relapse
    • Myelodysplastic syndromes (MDS) meeting the following criteria:

      • Must have high-risk features, including any of the following:

        • Intermediate-2 or high risk International Prognostic Scoring System (IPSS) score
        • Chronic myelomonocytic leukemia
      • Marrow blasts ≤ 20% (chemotherapy may be given to achieve target blast levels)
      • No rapidly progressive disease
    • Acute lymphoblastic leukemia meeting the following criteria:

      • Considered incurable with chemotherapy
      • Meets any of the following criteria:

        • High-risk cytogenetics (Ph+, t(4,11), 11q23 abnormalities, or monosomy 7)
        • Required > 1 induction course to achieve remission
        • Failed to enter remission
        • In second or subsequent remission
      • Marrow blasts ≤ 10% (chemotherapy may be given to achieve target blast levels)
    • Chronic myelogenous leukemia (CML) meeting 1 of the following criteria:

      • Chronic phase CML that failed imatinib mesylate therapy, as defined by progressive disease or failed to achieve a major cytogenetic response at 1 year after initiation of therapy
      • Accelerated phase CML meeting 1 of the following criteria:

        • Failed to achieve a complete cytogenetic remission at 1 year after initiation of therapy
        • Failed to achieve any cytogenetic response after 6 months of therapy
        • Progressive disease, as demonstrated by worsening cytogenetic response in 2 consecutive analyses separated by 4 weeks
      • In blast crisis with < 10% blasts in bone marrow
    • Multiple myeloma meeting the following criteria:

      • Stage I-III disease
      • Meets any of the following criteria:

        • In relapse after autologous transplantation
        • Refractory to ≥ 2 prior conventional myeloma therapies
        • Chromosome 13 abnormalities (may be enrolled at diagnosis or after initial progression)
    • Lymphoma

      • The following subtypes are eligible:

        • Diffuse large cell
        • Follicular large cell
        • Mantle cell
        • Peripheral T-cell
        • T-natural killer (T-NK) cell
        • Hodgkin's lymphoma
      • Must have progressed, recurred after prior therapy, or failed to respond to primary therapy
      • Relapsed disease after autologous stem cell transplantation (SCT) allowed
    • Low-grade non-Hodgkin's lymphoma meeting 1 of the following criteria:

      • Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
      • Relapsed after autologous SCT
    • Chronic lymphocytic leukemia

      • Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
      • Relapsed after autologous SCT
  • Meets 1 of the following criteria:

    • Age 55-70 years
    • Under age 55 and deemed ineligible for conventional high-dose chemotherapy, as indicated by any of the following:

      • Poor cardiac function (i.e., LVEF < 40%)
      • Poor pulmonary function (i.e., DLCO < 50%)
      • Hepatic dysfunction
      • Prior myeloablative therapy
  • Not eligible for autologous SCT or conventional therapy
  • Umbilical cord blood donor available

    • Matched at ≥ 4 of 6 HLA antigens (A, B, and DR)
    • Has 1-3 units of umbilical cord blood available
    • Must not have an HLA-identical or 1 antigen mismatched related donor or potential HLA-matched unrelated donor readily available 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:

  • ECOG performance status 0-2
  • Creatinine clearance > 40 mL/min
  • Creatinine < 2.0 mg/dL
  • AST and alkaline phosphatase < 3 times upper limit of normal (ULN)
  • Bilirubin < 2.0 mg/dL
  • Hepatitis C or active hepatitis B virus (HBV) allowed if ≤ grade 2 fibrosis and/or inflammation by liver biopsy

    • Patients with history of HBV infection should be tested for hepatitis B epsilon (HBe) antigen, anti-HBe, and HBV DNA (quantitative)
    • Patients with active HBV viral replication should receive antiviral therapy
  • Ejection fraction > 30%
  • DLCO ≥ 40%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active infection requiring ongoing antibiotic treatment
  • HIV negative

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00301951

Locations
United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0324
Sponsors and Collaborators
UCSF Helen Diller Family Comprehensive Cancer Center
Investigators
Principal Investigator: Thomas G. Martin, MD UCSF Helen Diller Family Comprehensive Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000465362, UCSF-04253, UCSF-2407, UCSF-H24045-25271-02
Study First Received: March 9, 2006
Last Updated: November 16, 2008
ClinicalTrials.gov Identifier: NCT00301951  
Health Authority: United States: Federal Government

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)
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
angioimmunoblastic T-cell lymphoma
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
anaplastic large cell lymphoma
nodal marginal zone B-cell lymphoma
previously treated myelodysplastic syndromes
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult diffuse large cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent small lymphocytic lymphoma

Study placed in the following topic categories:
Blast Crisis
Sezary syndrome
Chronic myelogenous leukemia
Chronic myelomonocytic leukemia
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Tacrolimus
Mycoses
Preleukemia
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Mycophenolate mofetil
Neoplasm Metastasis
Lymphoma, Large-Cell, Anaplastic
Acute myeloid leukemia, adult
Hodgkin Disease
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Acute myelogenous leukemia
Leukemia, Myeloid
Multiple Myeloma

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Disease
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Neoplasms by Site
Therapeutic Uses
Syndrome
Myeloablative Agonists
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 15, 2009