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Study of Stem Cell Transplant for Leukemia and Myelodysplastic Syndromes Using Clofarabine and Busulfan Regimen

Primary Purpose

Leukemia, Myelodysplastic Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Clofarabine with Busulfan
Sponsored by
Baylor Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring conditioning, preparative, clofarabine; transplant, Busulfan, leukemia, myelodysplastic syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Disease Criteria:

  • Acute myelogenous leukemia (AML)
  • Acute lymphocytic leukemia (ALL)
  • Myelodysplastic syndromes (MDS) Refractory anemia (RA) with adverse cytogenetics (SWOG criteria) or beyond (RAEB, RAEB-T, AML)
  • Other Myeloproliferative Disorders Myelofibrosis, Agnogenic Myeloid Metaplasia, Chronic Myelomonocytic Leukemia (CMML)
  • Chronic lymphocytic leukemia (CLL) High risk or advanced disease

Other Inclusion Criteria:

  • 18 years of age or older

  • Related or unrelated donor with HLA criteria as follows:

    • Related donors: a serologic equivalent HLA Class I (A, B, and C) and Class II DRB1 or DQB1 matched donor OR a donor who is a single 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci
    • Unrelated donors: sequence-based typing fully matched A, B, C, DRB1, and DQB1 allele-matched donor OR a donor who is no greater than 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci
  • Able to provide valid informed consent.
  • Female patients must have a negative serum pregnancy test within 2 weeks prior to enrollment.
  • Male and female patients must use an effective contraceptive method during the study and for up to 12 months after study treatment.

Exclusion Criteria:

Organ Function Criteria:

  • Cardiac: symptomatic coronary artery disease or ejection fraction <45% or uncontrolled cardiac failure
  • Pulmonary: FEV1 or DLCO (corrected) <50% of predicted values and/or receiving continuous supplementary oxygen
  • Hepatic: Bilirubin ≥ 1.2 mg/dL or AST/ALT ≥ 3x upper limit of normal (ULN) unless the liver is involved with malignant disease
  • Renal: creatinine clearance < 60 mL/min (24-hour urine collection) or <50 mL/min (Glofil test)
  • Karnofsky score <60%
  • Active CNS disease
  • Prior hematopoietic transplantation (autologous or allogeneic) <6 months prior to study entry
  • Use of investigational agents less than or equal to 30 days before study entry.
  • Life threatening, or clinically significant infection
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
  • Female patients who are pregnant or breast feeding
  • HIV-positive

Sites / Locations

  • Baylor University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Clofarabine with Busulfan

Arm Description

Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days

Outcomes

Primary Outcome Measures

Disease free survival at one and two year

Secondary Outcome Measures

Incidence of hematopoietic engraftment
Incidence and severity of acute toxicities
Pharmacokinetic profiles of high dose busulfan and standard dose clofarabine
Acute GVHD

Full Information

First Posted
February 25, 2009
Last Updated
April 1, 2013
Sponsor
Baylor Research Institute
Collaborators
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00852163
Brief Title
Study of Stem Cell Transplant for Leukemia and Myelodysplastic Syndromes Using Clofarabine and Busulfan Regimen
Official Title
Phase II Trial of Clofarabine With Parenteral Busulfan (Busulfex®) Followed by Allogeneic Related or Unrelated Donor Transplantation for the Treatment of Hematologic Malignancies and Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baylor Research Institute
Collaborators
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether Clofarabine in combination with Busulfan is effective as a preparative transplant regimen for the treatment of leukemia and myelodysplastic syndromes
Detailed Description
The success of allogeneic hematopoietic transplantation in the treatment of myeloid malignancies is determined by two main factors: the limiting of regimen-related toxicity and the prevention of recurrent leukemia. Over the past 10 years, considerable clinical research has been devoted to the reduction of regimen-related toxicity through the use of reduced-intensity (nonmyeloablative) transplants. However, leukemic relapse has remained a difficult obstacle. Thus, the need for highly effective, yet non-toxic regimens persists, particularly for elderly patients for whom very little overall progress has been made. Clofarabine is a chemotherapeutic agent with novel myelotoxic properties and proven low toxicity in older patients. These qualities suggest clofarabine may be a useful component of conditioning regimens for stem cell transplantation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndrome
Keywords
conditioning, preparative, clofarabine; transplant, Busulfan, leukemia, myelodysplastic syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clofarabine with Busulfan
Arm Type
Experimental
Arm Description
Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days
Intervention Type
Drug
Intervention Name(s)
Clofarabine with Busulfan
Other Intervention Name(s)
Clofarabine:CLOLAR, clofarabine; CAFdA; Cl-F-ara-A;, Busulfan: Busulfex™
Intervention Description
Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days
Primary Outcome Measure Information:
Title
Disease free survival at one and two year
Time Frame
At 1 year and 2 Year
Secondary Outcome Measure Information:
Title
Incidence of hematopoietic engraftment
Time Frame
100 days
Title
Incidence and severity of acute toxicities
Time Frame
100 days
Title
Pharmacokinetic profiles of high dose busulfan and standard dose clofarabine
Time Frame
Lesss than 8 days
Title
Acute GVHD
Time Frame
100 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Disease Criteria: Acute myelogenous leukemia (AML) Acute lymphocytic leukemia (ALL) Myelodysplastic syndromes (MDS) Refractory anemia (RA) with adverse cytogenetics (SWOG criteria) or beyond (RAEB, RAEB-T, AML) Other Myeloproliferative Disorders Myelofibrosis, Agnogenic Myeloid Metaplasia, Chronic Myelomonocytic Leukemia (CMML) Chronic lymphocytic leukemia (CLL) High risk or advanced disease Other Inclusion Criteria: 18 years of age or older Related or unrelated donor with HLA criteria as follows: Related donors: a serologic equivalent HLA Class I (A, B, and C) and Class II DRB1 or DQB1 matched donor OR a donor who is a single 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci Unrelated donors: sequence-based typing fully matched A, B, C, DRB1, and DQB1 allele-matched donor OR a donor who is no greater than 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci Able to provide valid informed consent. Female patients must have a negative serum pregnancy test within 2 weeks prior to enrollment. Male and female patients must use an effective contraceptive method during the study and for up to 12 months after study treatment. Exclusion Criteria: Organ Function Criteria: Cardiac: symptomatic coronary artery disease or ejection fraction <45% or uncontrolled cardiac failure Pulmonary: FEV1 or DLCO (corrected) <50% of predicted values and/or receiving continuous supplementary oxygen Hepatic: Bilirubin ≥ 1.2 mg/dL or AST/ALT ≥ 3x upper limit of normal (ULN) unless the liver is involved with malignant disease Renal: creatinine clearance < 60 mL/min (24-hour urine collection) or <50 mL/min (Glofil test) Karnofsky score <60% Active CNS disease Prior hematopoietic transplantation (autologous or allogeneic) <6 months prior to study entry Use of investigational agents less than or equal to 30 days before study entry. Life threatening, or clinically significant infection Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. Female patients who are pregnant or breast feeding HIV-positive
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Agura, MD
Organizational Affiliation
Baylor Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States

12. IPD Sharing Statement

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Study of Stem Cell Transplant for Leukemia and Myelodysplastic Syndromes Using Clofarabine and Busulfan Regimen

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