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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00852163
• Other study ID #: 006-150
• Status: Completed
• Phase: Phase 2
• First received: February 25, 2009
• Last updated: April 1, 2013
• Start date: March 2007
• Est. completion date: December 2011

Study information

• Verified date: April 2013
• Source: Baylor Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

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

Locations

Country	Name	City	State
United States	Baylor University Medical Center	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor Research Institute	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival at one and two year		At 1 year and 2 Year	No
Secondary	Incidence of hematopoietic engraftment		100 days	No
Secondary	Incidence and severity of acute toxicities		100 days	Yes
Secondary	Pharmacokinetic profiles of high dose busulfan and standard dose clofarabine		Lesss than 8 days	No
Secondary	Acute GVHD		100 Days	Yes