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: October 26, 2018
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief Summary:

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

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: August 1, 1995
• Actual Primary Completion Date: December 31, 2002
• Actual Study Completion Date: December 31, 2002

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose [ Time Frame: Study Duration 3 Years ]

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 55 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Texas

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

• Study Chair: Sergio Giralt, MD; M.D. Anderson Cancer Center

More Information

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00002831
• Other Study ID Numbers: DM94-064; P30CA016672 ( U.S. NIH Grant/Contract ); MDA-DM-94064 ( Other Identifier: UT MD Anderson Cancer Center ); NCI-G96-0999; CDR0000065033 ( Registry Identifier: NCI's PDQ Database )
• First Posted: July 29, 2004
• Last Update Posted: October 26, 2018
• Last Verified: October 2018

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; Cyclosporine; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Busulfan; Methotrexate; Decitabine; Tacrolimus; Cyclosporins; 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