Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan in Treating Patients With Hematologic Cancers

January 5, 2018 updated by: University of California, Davis

Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan

Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It also stops 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 cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of giving donor peripheral stem cell transplant together with fludarabine and busulfan and to see how well it works in treating patients with hematologic cancers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OUTLINE:

  • Conditioning regimen: Patients receive busulfan IV over 3 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
  • Allogeneic peripheral blood stem cell transplant (PBSC): Patients undergo allogeneic PBSC on day 0.
  • Immunosuppressive therapy/graft-versus-host disease (GVHD) prophylaxis: Patients achieve100% donor T-cell chimerism on day 30 without disease recurrence, and cyclosporine A (CSA) IV continuously over 24 hours or orally every 12 hours on days -1 to 60 followed by a taper until day 100 and oral mycophenolate mofetil (MMF) once every 12 hours on days 1-40, in the absence of ≥ grade 2 GVHD.

Patients with recurrent disease or < 100% donor T-cell chimerism (on day 30) undergo a 12-day CSA and MMF taper followed by escalating doses of previously collected donor leukocyte infusion every 4 weeks until 100% donor T-cell chimerism or disease regression, in the absence of ≥ grade 2 GVHD.

After completion of study treatment, patients are followed periodically.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

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
      • Sacramento, California, United States, 95817
        • University of California Davis 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 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosed with any of the following:

    • Acute myeloid leukemia (AML), meeting 1 of the following criteria:

      • Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
      • In first complete remission (CR1) with poor-risk cytogenetics, antecedent hematological disease (i.e., myelodysplasia), or treatment-related leukemia

    • Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

      • Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
      • CR1 with Philadelphia chromosome or poor-risk cytogenetics

    • Chronic myelogenous leukemia (CML), meeting the following criteria:

      • First or second chronic phase

        • Must be documented disease progression after imatinib mesylate therapy OR documented lack of cytogenetic response 6 months post-imatinib mesylate initiation OR imatinib mesylate intolerance

    • Chronic lymphocytic leukemia (CLL), meeting the following criteria:

      • Recurrent disease after fludarabine-based therapy

        • Must have chemosensitive disease at the time of relapse, defined as greater than 50% reduction of WBC and lymphadenopathy

    • Recurrent Hodgkin lymphoma, recurrent non-Hodgkin lymphoma (NHL) (low-, intermediate-, or high-grade disease*), or transformed NHL, meeting 1 of the following criteria:

      • Received prior autologous transplantation and cytoreductive therapy at the time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu) as defined by the International Workshop
      • Relapsed disease that required more than 2 salvage regimens to achieve CR or CRu

    • Recurrent multiple myeloma, meeting the following criteria:

      • Must have received prior autologous transplantation and demonstrate chemosensitivity at the time of relapse, defined as greater than 50% reduction of M-component or plasma-cell marrow infiltration

    • Myelodysplastic syndrome

      • Refractory anemia (RA)/RA with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD)/refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD-RS), or RA with excess blasts (RAEB) I, meeting the following criteria:

        • Must be transfusion-dependent and have an IPSS score ≥ 1.5, based on WHO criteria
        • No RAEB II or del(5q)
  • No uncontrolled CNS metastases
  • 5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor (both patient and donor) available

PATIENT CHARACTERISTICS:

  • Karnofsky performance status ≥ 50%
  • Serum creatinine ≤ 2 mg/dL
  • Not pregnant
  • Fertile patients must use effective contraception

  • 50 years of age or older

    • Patients 18-50 years of age are eligible if meeting 1 of the following criteria:

      • Have a preexisting medical condition
      • Received prior therapy (i.e., autologous transplantation) and are considered to be too high risk for conventional myeloablative transplantation
  • Must be willing to accept or comprehend irreversible sterility as a side effect of therapy
  • No uncontrolled active infection
  • No psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
  • Cardiac ejection fraction ≥ 30%
  • Corrected pulmonary-diffusing capacity ≥ 35%
  • No serologic evidence of infection with HIV
  • No decompensated liver disease with serum bilirubin > 2.0 mg/dL

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
Other: RIST for Heme malignancies
Busulfan 3.3 mg/kg over 3 hours on day -6 and day -5 Fludarabine 30 mg/m2 IV over 30 minutes on day -6 to day -2 followed by Transplant followed by Immunosuppressive/GVHD therapy
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: busulfan
Procedure: peripheral blood stem cell transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Day 100 Transplant-related Mortality
Time Frame: 24 months after day 100 transplant
Patients were followed for death and whether or not that death was attributed to the day 100 transplant via physician assessment for 24 months after day 100 transplant.
24 months after day 100 transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Without Progression After Day 100 Transplant
Time Frame: 24 months after day 100 transplant
All patients will be followed for progression for 24 months after their day 100 transplant.
24 months after day 100 transplant
Number of Patients Alive 24 Months Post Day 100 Transplant
Time Frame: 24 months post day 100 transplant
Patients will be followed for survival for 24 months post day 100 transplant.
24 months post day 100 transplant

Collaborators and Investigators

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

Sponsor

University of California, Davis

Investigators

  • Study Chair: Carol M. Richman, MD, University of California, Davis

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

June 1, 2007

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

February 20, 2008

First Submitted That Met QC Criteria

February 20, 2008

First Posted (Estimate)

February 21, 2008

Study Record Updates

Last Update Posted (Actual)

January 10, 2018

Last Update Submitted That Met QC Criteria

January 5, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCDCC#196
  • 288263 (Other Identifier: UC Davis)
  • UCD-196 (Other Identifier: UCDCC)

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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