Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous or Acute Leukemia
|ClinicalTrials.gov Identifier: NCT00002831|
Recruitment Status : Completed
First Posted : July 29, 2004
Last Update Posted : July 31, 2012
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.
PURPOSE: Phase I/II trial to study the effectiveness of high-dose chemotherapy plus peripheral stem cell transplantation in treating patients with chronic myelogenous or acute leukemia.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Biological: Filgrastim Drug: Busulfan Drug: Cyclophosphamide Drug: Cyclosporine Drug: Decitabine (DAC) Drug: Methotrexate Drug: Methylprednisolone Drug: Tacrolimus Procedure: Allogeneic Bone Marrow Transplantation Procedure: Peripheral Blood Stem Cell Transplantation||Phase 1 Phase 2|
OBJECTIVES: I. Determine the maximum tolerated dose of decitabine in combination with busulfan and cyclophosphamide in patients with hematologic malignancies. II. Establish the pharmacokinetics of decitabine and busulfan in this patient population. III. Determine the effectiveness of this combination in achieving durable complete remission in patients with chronic myelogenous leukemia (CML) in blast crisis or acute myelogenous leukemia (AML) in relapse undergoing allogeneic stem cell transplantation.
OUTLINE: In cohorts of 3, patients receive escalating doses of decitabine (DAC) IV over 4 hours on days -8 and -7. Busulfan is administered orally every 6 hours on consecutive days -6 through -4. Cyclophosphamide is given by vein (IV) over 1 hour on consecutive days -3 and -2. The maximum tolerated dose of DAC is defined as the dose at which 2 patients experience dose limiting toxicity. Donors receive filgrastim subcutaneously (SQ) daily every 12 hours starting 2-4 days prior to the first stem cell collection and before DAC infusion. Leukapheresis is conducted daily. If insufficient number of cells are collected, blood marrow is harvested for supplementation. Stem cells are infused on day 0. For graft vs host disease prophylaxis (GVHD), patients receive tacrolimus IV beginning one day before stem cell infusion, then orally following tolerance to tacrolimus. Patients intolerant to tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment. All patients receive methylprednisolone given according to clinical grade of GVHD procedures. For CNS prophylaxis, methotrexate is given intrathecally or intraventricularly monthly, beginning on the second month through the eighth month of treatment. Allogeneic patients are followed until the end of 1 year.
PROJECTED ACCRUAL: An estimated 30 allogeneic recipients will be recruited in 2 years for the expected study duration of 2-3 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of High-Dose Deoxyazacytidine, Busulfan, and Cyclophosphamide With Allogeneic Stem Cell Transplantation for Hematologic Malignancies|
|Study Start Date :||July 1994|
|Primary Completion Date :||December 2002|
|Study Completion Date :||December 2002|
Experimental: Deoxyazacytidine + Busulfan + Cyclophosphamide
Deoxyazacytidine + Busulfan + Cyclophosphamide With Allogeneic Stem Cell Transplantation
Subcutaneously (SQ) daily every 12 hours starting 2-4 days prior to the first stem cell collection and before DAC infusion.
Other Names:Drug: Busulfan
Administered orally every 6 hours on consecutive days -6 through -4.
Other Names:Drug: Cyclophosphamide
Given intravenously (IV) over 1 hour on consecutive days -3 and -2.
Other Names:Drug: Cyclosporine
Patients intolerant to tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment.
Other Names:Drug: Decitabine (DAC)
IV over 4 hours on days -8 and -7.
Other Name: DacogenDrug: Methotrexate
Given intrathecally or intraventricularly monthly, beginning on the second month through the eighth month of treatment.Drug: Methylprednisolone
Given according to clinical grade of GVHD procedures.
Other Names:Drug: Tacrolimus
IV beginning one day before stem cell infusion, then orally following tolerance to tacrolimus.
Other Name: PrografProcedure: Allogeneic Bone Marrow Transplantation
Infusion of stem cells on Day 0.
Other Name: ABMTProcedure: Peripheral Blood Stem Cell Transplantation
Stem cell infusion on Day 0.
Other Name: PBSCT
- Maximum Tolerated Dose [ Time Frame: Study Duration 3 Years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002831
|United States, Texas|
|University of Texas - MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Chair:||Sergio Giralt, MD||M.D. Anderson Cancer Center|