Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen

October 30, 2017 updated by: University of Michigan Rogel Cancer Center

Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity conditioning (Clo/BU4 regimen) prior to transplant and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for stem cell transplant in the treatment of aggressive hematologic malignancies in subjects where more conventional approaches are failing.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Transplants with stem cells collected from the blood of an unrelated donor (allo-HSCT) are being used more commonly for many blood cancers which are not curable with more conventional methods of chemotherapy. Although allo-HSCT has great potential, there are still high risks due to infections, graft-versus-host disease (GVHD), where the donor's cells attack the recipient's tissues as foreign, and due to toxic effects of the chemotherapy drugs given to prepare (or condition) the recipient's bone marrow for transplant.

As a reduced intensity conditioning, a combination of Fludarabine and a lower dose of Busulfan (Flu/BU2) is one of the most popular regimens. Among full-intensity regimens, a combination of Fludarabine and standard-dose Busulfan (Flu/BU4) has been investigated recently and shown to be very well tolerated.

Clofarabine, similar to Fludarabine, is known to have a stronger anti-tumor effect than Fludarabine and has shown promise in treating aggressive acute leukemias. In addition, evidence is that it is well-tolerated with manageable side effects especially in older subjects. Thus replacing Fludarabine with Clofarabine in a full-intensity transplant regimen, Clo/BU4 may provide a regimen with increased anti-tumor activity without adding significant risks of toxicity.

The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity regimen (Clo/BU4) and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for HSCT in the treatment for aggressive hematologic malignancies, in subjects where more conventional approaches are failing.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2
  • 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
    • Michigan
      • Ann Arbor, Michigan, United States, 48170
        • University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

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

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Disease Criteria

  • Acute leukemia or chronic myelogenous leukemia in blastic crisis or accelerated phase, not in remission at the time of transplant
  • Myelodysplastic syndrome, with more than 5% blasts in bone marrow at the time of transplant
  • Hodgkin and Non-Hodgkin Lymphomas: Not in CR in PET scan or CT scan before transplant, or relapsed within 1 year from previous remission
  • CLL not in remission
  • Multiple Myeloma, not in remission
  • Suitable donor available (related or unrelated)

Age, Organ Function Criteria

  • Age: ≤ 70 years
  • Cardiac: LV Ejection Fraction ≥ 40% by MUGA or Echocardiogram
  • Pulmonary: FEV1 and FVC ≥ 40% predicted, and DLCO (corrected for hemoglobin) ≥ 40% of predicted
  • Renal: Adult population: serum creatinine ≤ 1.0 mg/dL (if serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation)
  • Renal: Pediatric population: serum creatinine clearance ≥ 90 ml/min/1.73 m2 as calculated by the Schwartz formula for estimated GFR
  • Hepatic: serum total bilirubin ≤ 2.0 mg/dl and AST / ALT ≤ ULN x 4
  • Performance status: Karnofsky ≥ 70%

Exclusion Criteria:

  • Other active life-threatening cancer requiring treatment other than allo-HSCT
  • HIV1 or HIV2 positive
  • Uncontrolled medical or psychiatric disorder
  • Uncontrolled viral or fungal infection
  • Active CNS leukemia
  • Non-compliant to medications
  • No appropriate caregivers identified

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: Clo/BU4

Study will start at the 2nd dose level of three Clofarabine levels, in combination with Busulfan. The Clofarabine level that each subsequent patient is treated at is determined by a method using continual reassessment.

After pre-conditioning, subjects will receive a peripheral blood stem cell transplant.
Drug: Clofarabine/Busulfan x 4

Clofarabine IV (dose levels)

  • 1st dose level: 20 mg/m2/day x 5 days
  • 2nd dose level: 30 mg/m2/day x 5 days
  • 3rd dose level: 40 mg/m2/day x 5 days

Busulfan IV 3.2 mg/kg daily x 4 days

Procedure: Peripheral blood stem cell transplant
Peripheral blood stem cell transplant, after pre-conditioning drug treatment
Radiation: Total Lymphoid Irradiation
Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Regimen Related Toxicities
Time Frame: two years
The incidence of non-hematological toxicities (Common Terminology Criteria for Adverse Events (CTCAE) 3.0) from initiation of conditioning to Day + 30 or toxicities after day +30, possibly, probably or definitely related to conditioning for all patients treated with Clofarabine (independent of dose level).
two years
One-year Overall Survival Rate for AML
Time Frame: 1 year
Percent Overall Survival (OS) for at one year for subjects with Acute Myeloid Leukemia (AML).
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Two-year Overall Survival for All Cases.
Time Frame: 2 years
Percent Overall Survival (OS) at two years for all patients.
2 years
Five Year Overall Survival for All Cases
Time Frame: five years
The number of patients alive at 5 years
five years

Collaborators and Investigators

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

Sponsor

University of Michigan Rogel Cancer Center

Collaborators

Genzyme, a Sanofi Company

Investigators

  • Principal Investigator: John Magenau, M.D., University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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, 2007

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

November 8, 2007

First Submitted That Met QC Criteria

November 9, 2007

First Posted (Estimate)

November 12, 2007

Study Record Updates

Last Update Posted (Actual)

December 5, 2017

Last Update Submitted That Met QC Criteria

October 30, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCC 2007.055

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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