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

August 13, 2013 updated by: University of California, San Francisco

Pilot Study of Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: cord blood transplant
Drug: prednisone
Drug: etoposide
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: busulfan
Biological: sargramostim
Drug: tacrolimus
Procedure: umbilical cord blood transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
up to 24 months post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Thomas G. Martin, MD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2002

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

March 15, 2006

First Submitted That Met QC Criteria

March 15, 2006

First Posted (Estimate)

March 17, 2006

Study Record Updates

Last Update Posted (Estimate)

August 14, 2013

Last Update Submitted That Met QC Criteria

August 13, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000463370
  • UCSF-02253
  • UCSF-H24045-21269-04
  • UCSF-2207

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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