Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

October 9, 2018 updated by: Damiano Rondelli, MD, University of Illinois at Chicago
New conditioning regimens are still needed to maximize efficacy and limit treatment-related deaths of allogeneic transplantation for advanced hematologic malignancies. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Treatment-related mortality and recurrence of disease account for the majority of treatment failures in allogeneic transplantation for advanced hematologic malignancies. The most commonly utilized conditioning regimens consist of cyclophosphamide and total-body irradiation or busulfan and cyclophosphamide. Other agents such as etoposide or thiotepa are sometimes added to maximize the antileukemic effect. New conditioning regimens are however still needed to maximize efficacy and limit treatment-related deaths. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

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
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago Medical 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

10 years to 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with the following diseases:

    • Acute myeloid or lymphocytic leukemia in first remission at standard or high-risk for recurrence.
    • Acute leukemia in greater than or equal to second remission, or with early relapse, or partial remission.
    • Chronic myelogenous leukemia in accelerated phase or blast-crisis.
    • Chronic myelogenous leukemia in chronic phase
    • Recurrent or refractory malignant lymphoma or Hodgkin's disease
    • Multiple myeloma.
    • Chronic lymphocytic leukemia, relapsed or with poor prognostic features.
    • Myeloproliferative disorder (polycythemia vera, myelofibrosis) with poor prognostic features.
    • Severe aplastic anemia after failure of immunosuppressive therapy.
  • Age 10-65 years.
  • Zubrod performance status less than or equal to 2.
  • Adequate cardiac and pulmonary function. Patients with decreased LVEF < 40% or DLCO < 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol.
  • Patient or guardian able to sign informed consent.

Exclusion Criteria:

  • Life expectancy is severely limited by concomitant illness.
  • Serum creatinine greater than 1.5 mg/dL or Creatinine Clearance less than 50 ml/min .
  • Serum bilirubin greater than or equal to 2.0 mg/dl, SGPT greater than 3 x upper limit of normal
  • Evidence of chronic active hepatitis or cirrhosis
  • HIV-positive
  • Patient is pregnant

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: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Arm 1
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
Drug: fludarabine/busulfan
All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
Other Names:
  • Fludara
  • Busulfex
  • Fludarabine Phosphate
  • Myleran
  • Fludarabine:
  • Busulfan:
Drug: ATG
Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen.
Other Names:
  • Thymoglobulin
ACTIVE_COMPARATOR: Arm 2
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
Drug: ATG
Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen.
Other Names:
  • Thymoglobulin
Drug: fludarabine/ melphalan
All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl).
Other Names:
  • Fludara
  • Alkeran
  • Fludarabine phosphate
  • Fludarabine:
  • Melphalan:

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Engraftment.
Time Frame: Up to 30 days post-transplant
Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant.
Up to 30 days post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants With 100 Day Transplant-related Mortality.
Time Frame: Up to 100 days post-transplant.
Day 100 transplant-related mortality was measured in both groups.
Up to 100 days post-transplant.
Time to ANC and Platelet Engraftment
Time Frame: Up to 30 days post-transplant
Days to ANC or platelet engraftment
Up to 30 days post-transplant
Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD).
Time Frame: Up to 100 days post-transplant (acute GVHD).
Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant.
Up to 100 days post-transplant (acute GVHD).

Collaborators and Investigators

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

Sponsor

University of Illinois at Chicago

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

February 1, 2000

Primary Completion (ACTUAL)

May 1, 2013

Study Completion (ACTUAL)

May 1, 2013

Study Registration Dates

First Submitted

November 23, 2011

First Submitted That Met QC Criteria

December 21, 2011

First Posted (ESTIMATE)

December 26, 2011

Study Record Updates

Last Update Posted (ACTUAL)

November 8, 2018

Last Update Submitted That Met QC Criteria

October 9, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000-0117

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

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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