Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen
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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 |
- 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 ]
- 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)
Busulfan IV 3.2 mg/kg daily x 4 days 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 |
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| United States, Michigan | |
| University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program | |
| Ann Arbor, Michigan, United States, 48170 | |
| 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:
|
Hodgkin Disease Leukemia Lymphoma Lymphoma, Non-Hodgkin Multiple Myeloma Neoplasms, Plasma Cell Myelodysplastic Syndromes Preleukemia Hematologic Neoplasms 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 Neoplasms by Site Busulfan Clofarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on October 17, 2012
