Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous or Acute Leukemia
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Purpose
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 | Intervention | 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 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I/II Study of High-Dose Deoxyazacytidine, Busulfan, and Cyclophosphamide With Allogeneic Stem Cell Transplantation for Hematologic Malignancies |
- Maximum Tolerated Dose [ Time Frame: Study Duration 3 Years ] [ Designated as safety issue: Yes ]
| Enrollment: | 24 |
| Study Start Date: | July 1994 |
| Study Completion Date: | December 2002 |
| Primary Completion Date: | December 2002 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Deoxyazacytidine + Busulfan + Cyclophosphamide
Deoxyazacytidine + Busulfan + Cyclophosphamide With Allogeneic Stem Cell Transplantation
|
Biological: Filgrastim
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: Dacogen
Drug: 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: Prograf
Procedure: Allogeneic Bone Marrow Transplantation
Infusion of stem cells on Day 0.
Other Name: ABMT
Procedure: Peripheral Blood Stem Cell Transplantation
Stem cell infusion on Day 0.
Other Name: PBSCT
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 15 Years to 55 Years (Child, Adult) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Acute leukemia past first remission or induction failure Chronic myelogenous leukemia in accelerated phase or blast crisis
PATIENT CHARACTERISTICS: Age: 15 to 55 Performance status: Zubrod 0-2 Life expectancy: Life expectancy not severely limited by concurrent illness Hematopoietic: Not specified Hepatic: No evidence of chronic active hepatitis or cirrhosis Bilirubin no greater than 2 times upper limit of normal SGPT no greater than 4 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: Left ventricular ejection fraction at least 50% No uncontrolled arrhythmias or symptomatic cardiac disease Pulmonary: FEV1, FVC, and DLCO at least 50% No symptomatic pulmonary disease Other: Related donor who is HLA-identical required No effusion or ascites greater than 1 L prior to drainage HIV negative Not pregnant No active CNS disease
PRIOR CONCURRENT THERAPY: Not specified
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: 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 |
More Information
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00002831 History of Changes |
| Other Study ID Numbers: | DM94-064 P30CA016672 MDA-DM-94064 NCI-G96-0999 CDR0000065033 |
| Study First Received: | November 1, 1999 |
| Last Updated: | July 27, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by M.D. Anderson Cancer Center:
|
recurrent adult acute myeloid leukemia accelerated phase chronic myelogenous leukemia blastic phase chronic myelogenous leukemia |
Additional relevant MeSH terms:
|
Leukemia Neoplasms by Histologic Type Neoplasms Cyclophosphamide Methotrexate Cyclosporins Cyclosporine Busulfan Tacrolimus Decitabine Methylprednisolone Hemisuccinate Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone |
Prednisolone hemisuccinate Prednisolone phosphate Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Antimetabolites, Antineoplastic |
ClinicalTrials.gov processed this record on September 26, 2016