Clinical trial NCT00556452: Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Multiple Myeloma
Myelodysplastic Syndrome
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2007-11-12
Enrollment: 46
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Regimen Related Toxicities
timeFrame: two years
measure: One-year Overall Survival Rate for AML
timeFrame: 1 year
Secondary outcomes:
measure: Two-year Overall Survival for All Cases.
timeFrame: 2 years
measure: Five Year Overall Survival for All Cases
timeFrame: five years
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program
state: Michigan
Study officials:
affiliation: University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program
name: John Magenau, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Magenau J, Tobai H, Pawarode A, Braun T, Peres E, Reddy P, Kitko C, Choi S, Yanik G, Frame D, Harris A, Erba H, Kujawski L, Elenitoba-Johnson K, Sanks J, Jones D, Paczesny S, Ferrara J, Levine J, Mineishi S. Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies. Blood. 2011 Oct 13;118(15):4258-64. doi: 10.1182/blood-2011-06-358010. Epub 2011 Aug 12.