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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by University of Michigan Cancer Center.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00556452
First received: November 8, 2007
Last updated: August 7, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Leukemia
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Multiple Myeloma
Myelodysplastic Syndrome
Drug: Clofarabine/Busulfan x 4
Procedure: Peripheral blood stem cell transplant
Radiation: Total Lymphoid Irradiation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Two-year overall and disease-free survival of all cases. [ Time Frame: two years ] [ Designated as safety issue: Yes ]
  • Five-year overall and disease-free survival of all cases. [ Time Frame: five years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 45
Study Start Date: October 2007
Estimated Study Completion Date: September 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: 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

Procedure: Peripheral blood stem cell transplant
Peripheral blood stem cell transplant, after pre-conditioning drug treatment
Radiation: Total Lymphoid Irradiation
Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

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

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00556452

Locations
United States, Michigan
University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program
Ann Arbor, Michigan, United States, 48170
Sponsors and Collaborators
University of Michigan Cancer Center
Genzyme, a Sanofi Company
Investigators
Principal Investigator: John Magenau, M.D. University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program
  More Information

No publications provided by University of Michigan Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00556452     History of Changes
Other Study ID Numbers: UMCC 2007.055
Study First Received: November 8, 2007
Last Updated: August 7, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Hodgkin Disease
Myelodysplastic Syndromes
Preleukemia
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Busulfan
Clofarabine
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014