Clinical trial NCT00852163: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndrome
Keywords: conditioning, preparative
clofarabine; transplant
Busulfan
leukemia
myelodysplastic syndrome
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2009-02-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease free survival at one and two year
timeFrame: At 1 year and 2 Year
Secondary outcomes:
measure: Incidence of hematopoietic engraftment
timeFrame: 100 days
measure: Incidence and severity of acute toxicities
timeFrame: 100 days
measure: Pharmacokinetic profiles of high dose busulfan and standard dose clofarabine
timeFrame: Lesss than 8 days
measure: Acute GVHD
timeFrame: 100 Days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: Baylor Health Care System
name: Edward Agura, MD
role: PRINCIPAL_INVESTIGATOR
References: