Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer

October 10, 2017 updated by: University of California, San Francisco

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

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, 94143-0324
        • UCSF 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 70 years (Adult, Older 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:

      • 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

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
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Drug: busulfan
Biological: sargramostim
Drug: tacrolimus
Drug: mycophenolate mofetil
Procedure: umbilical cord blood transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Feasibility of donor cord blood transplant
Time Frame: up to 36 months post transplant
as determined by > 80% engraftment rate at day 180 and a < 50% transplant-related mortality rate at day 100
up to 36 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

  • Principal Investigator: 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

September 1, 2004

Primary Completion (Actual)

July 1, 2009

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

March 9, 2006

First Submitted That Met QC Criteria

March 9, 2006

First Posted (Estimate)

March 13, 2006

Study Record Updates

Last Update Posted (Actual)

October 12, 2017

Last Update Submitted That Met QC Criteria

October 10, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000465362
  • UCSF-04253
  • UCSF-2407
  • UCSF-H24045-25271-02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

Clinical Trials on Lymphoma

Clinical Trials on anti-thymocyte globulin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bangladesh

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe