Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous or Acute Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00002831
First received: November 1, 1999
Last updated: July 27, 2012
Last verified: July 2012
  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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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:
  • C-CSF
  • Neupogen
Drug: Busulfan
Administered orally every 6 hours on consecutive days -6 through -4.
Other Names:
  • Busulfex
  • Myleran
Drug: Cyclophosphamide
Given intravenously (IV) over 1 hour on consecutive days -3 and -2.
Other Names:
  • Cytoxan
  • Neosar
Drug: Cyclosporine
Patients intolerant to tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment.
Other Names:
  • Sandimmune
  • CYA
  • Cyclosporin A
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:
  • Depo-Medrol
  • Medrol
  • Solu-Medrol
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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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: NCT00002831

Locations
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Sergio Giralt, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

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
Cyclosporins
Cyclosporine
Tacrolimus
Methotrexate
Busulfan
Decitabine
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents

ClinicalTrials.gov processed this record on September 22, 2014