This trial is active, not recruiting.

Conditions leukemia, hodgkin lymphoma, non-hodgkin lymphoma, multiple myeloma, myelodysplastic syndrome
Treatments clofarabine/busulfan x 4, peripheral blood stem cell transplant, total lymphoid irradiation
Phase phase 1/phase 2
Sponsor University of Michigan Cancer Center
Collaborator Genzyme, a Sanofi Company
Start date October 2007
End date June 2011
Trial size 45 participants
Trial identifier NCT00556452, UMCC 2007.055


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose prevention
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.
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
peripheral blood stem cell transplant
Peripheral blood stem cell transplant, after pre-conditioning drug treatment
total lymphoid irradiation
Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

Primary Outcomes

To establish the toxicity profile of three doses of Clofarabine in combination with Busulfan and assess the one-year overall survival rate for subjects receiving the dose of Clofarabine with a DLT rate closest to 20%.
time frame: one year

Secondary Outcomes

Two-year overall and disease-free survival of all cases.
time frame: two years
Five-year overall and disease-free survival of all cases.
time frame: five years

Eligibility Criteria

Male or female participants up to 70 years old.

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

Additional Information

Official title Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen
Principal investigator John Magenau, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2012.
Information provided to ClinicalTrials.gov by University of Michigan Cancer Center.