Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen

NCT ID: NCT00556452

Last Updated: 2017-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2012-09-30

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.

Conditions

Leukemia; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Clo/BU4

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.

Group Type: EXPERIMENTAL

Clofarabine/Busulfan x 4

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

Peripheral blood stem cell transplant, after pre-conditioning drug treatment

Total Lymphoid Irradiation

Intervention Type: RADIATION

Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

Interventions

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

Intervention Type: DRUG

Peripheral blood stem cell transplant

Peripheral blood stem cell transplant, after pre-conditioning drug treatment

Intervention Type: PROCEDURE

Total Lymphoid Irradiation

Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

Intervention Type: RADIATION

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

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Magenau, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

Locations

University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program

Ann Arbor, Michigan, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 21841163 (View on PubMed)

Other Identifiers

UMCC 2007.055

Identifier Type: -

Identifier Source: org_study_id