Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00304018
First received: March 15, 2006
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and etoposide, before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer 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 before transplant and tacrolimus and prednisone after transplant may stop this from happening.

PURPOSE: This phase I trial is studying how well donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Biological: anti-thymocyte globulin
Biological: sargramostim
Drug: busulfan
Drug: etoposide
Drug: fludarabine phosphate
Drug: prednisone
Drug: tacrolimus
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: umbilical cord blood transplantation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies [ Time Frame: up to 24 months post-transplant ] [ Designated as safety issue: Yes ]
    Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies, in terms of > 80% engraftment rate at day 100 post-transplant and ≤ 50% transplant-related mortality.


Enrollment: 5
Study Start Date: October 2002
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cord blood transplant Biological: anti-thymocyte globulin Biological: sargramostim Drug: busulfan Drug: etoposide Drug: fludarabine phosphate Drug: prednisone Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies, in terms of > 80% engraftment rate at day 100 post-transplant and ≤ 50% transplant-related mortality.

Secondary

  • Determine the toxicity of a myeloablative preparative regimen comprising busulfan, fludarabine, and etoposide prior to UCBT in these patients.
  • Determine the neutrophil and platelet recovery in patients treated with this regimen.
  • Determine the event-free and overall survival of patients treated with this regimen.
  • Evaluate lineage-specific chimerism after UCBT and assess the contribution of each individual cord blood unit to post-transplantation hematopoiesis in these patients.
  • Determine the incidence, severity, and timing of acute and chronic graft-vs-host disease in patients treated with this regimen.

OUTLINE: This is a pilot study.

  • Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours 4 times daily on days -7 and -4, etoposide IV over 4 hours on day -3, and anti-thymocyte globulin IV over 6 hours on days -2 and -1.
  • Donor umbilical cord blood transplantation (UCBT): Patients undergo donor UCBT on day 0. Beginning on day 7, patients receive sargramostim (GM-CSF) IV or subcutaneously once daily until blood counts recover.
  • Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally twice daily beginning on day -2 and continuing until day 180 followed by a taper. Patients also receive oral prednisone twice daily on days 13-50 and then once daily on days 50-60, followed by a rapid taper.

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

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

  Eligibility

Ages Eligible for Study:   18 Years to 55 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:

      • Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:

        • High-risk cytogenetics (-7, -7q, -5, -5q, t[6,9], t[9,11], complex, Philadelphia chromosome positive [Ph+])
        • AML evolved from prior myelodysplasia
        • AML secondary to prior chemotherapy
        • Failed to achieve remission
        • In second or subsequent remission
      • Marrow blasts ≤ 10% (may be achieved using chemotherapy)
    • Myelodysplastic syndromes (MDS) with high-risk features

      • International Prognostic Scoring System (IPSS) score intermediate -2 or high-risk
      • Marrow blasts ≤ 20% (may be achieved using chemotherapy)
    • Acute lymphoblastic leukemia meeting the following criteria:

      • Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:

        • High-risk cytogenetics (Ph+, t[4,11], 11q23 abnormalities, and monosomy 7)
        • Required > 1 induction course to achieve remission
        • Failed to achieve remission
        • In second or subsequent remission
      • Marrow blasts ≤ 10% (may be achieved using chemotherapy)
    • Chronic myelogenous leukemia meeting ≥ 1 of the following criteria:

      • Accelerated phase
      • Chronic phase refractory to imatinib mesylate
      • Blastic phase

        • Marrow blasts ≤ 10% (may be achieved using chemotherapy)
    • Multiple myeloma meeting 1 of the following criteria:

      • Stage II or III disease with > first relapse or refractory disease
      • Newly diagnosed disease with chromosome 13 abnormalities
    • Lymphoma meeting the following criteria:

      • One of the following subtypes:

        • Diffuse large cell lymphoma
        • Mantle cell lymphoma
        • Peripheral T-cell lymphoma
        • T-natural killer (NK) cell lymphoma
        • Hodgkin's lymphoma
      • Disease failed to respond to primary therapy, progressed, or recurred after prior therapy

        • Patients who have failed autologous stem cell transplantation are eligible provided it has been > 1 year since transplant
  • No rapid progression of malignant disease
  • Not eligible for autologous stem cell transplantation
  • Available umbilical cord blood (1-3 units) donor matching at ≥ 4 of 6 HLA antigens (A, B, and DR)

    • Patients with an HLA-identical or 1 antigen-mismatched related donor OR a potential HLA-matched unrelated donor matching at > 6/8 (A, B, C, DR) alleles are not eligible

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Creatinine < 2.0 mg/dL
  • Creatinine clearance > 40 mL/min
  • Bilirubin < 2.0 mg/dL
  • AST and alkaline phosphatase < 3 times upper limit of normal
  • Hepatitis C and active hepatitis B allowed if patient has ≤ grade 2 inflammation or fibrosis by liver biopsy
  • Ejection fraction > 40% by echocardiogram or MUGA
  • DLCO > 40% of predicted
  • Not pregnant or nursing
  • Negative pregnancy test
  • No known HIV infection
  • No active infection requiring ongoing antibiotic treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00304018

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Study Chair: Thomas G. Martin, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00304018     History of Changes
Other Study ID Numbers: CDR0000463370, UCSF-02253, UCSF-H24045-21269-04, UCSF-2207
Study First Received: March 15, 2006
Last Updated: August 13, 2013
Health Authority: United States: Federal Government

Keywords provided by University of California, San Francisco:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
recurrent adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
refractory multiple myeloma
adult acute lymphoblastic leukemia in remission
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
stage II multiple myeloma
stage III multiple myeloma
recurrent adult acute lymphoblastic leukemia
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
recurrent adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
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)
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
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
Neoplasms by Site
Antilymphocyte Serum
Busulfan
Fludarabine phosphate
Tacrolimus
Fludarabine
Etoposide

ClinicalTrials.gov processed this record on August 20, 2014