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

NCT ID: NCT00002831

Last Updated: 2018-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-08-01

Study Completion Date

2002-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Deoxyazacytidine + Busulfan + Cyclophosphamide

Deoxyazacytidine + Busulfan + Cyclophosphamide With Allogeneic Stem Cell Transplantation

Group Type EXPERIMENTAL

Filgrastim

Intervention Type BIOLOGICAL

Subcutaneously (SQ) daily every 12 hours starting 2-4 days prior to the first stem cell collection and before DAC infusion.

Busulfan

Intervention Type DRUG

Administered orally every 6 hours on consecutive days -6 through -4.

Cyclophosphamide

Intervention Type DRUG

Given intravenously (IV) over 1 hour on consecutive days -3 and -2.

Cyclosporine

Intervention Type DRUG

Patients intolerant to tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment.

Decitabine (DAC)

Intervention Type DRUG

IV over 4 hours on days -8 and -7.

Methotrexate

Intervention Type DRUG

Given intrathecally or intraventricularly monthly, beginning on the second month through the eighth month of treatment.

Methylprednisolone

Intervention Type DRUG

Given according to clinical grade of GVHD procedures.

Tacrolimus

Intervention Type DRUG

IV beginning one day before stem cell infusion, then orally following tolerance to tacrolimus.

Allogeneic Bone Marrow Transplantation

Intervention Type PROCEDURE

Infusion of stem cells on Day 0.

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Stem cell infusion on Day 0.

Interventions

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Filgrastim

Subcutaneously (SQ) daily every 12 hours starting 2-4 days prior to the first stem cell collection and before DAC infusion.

Intervention Type BIOLOGICAL

Busulfan

Administered orally every 6 hours on consecutive days -6 through -4.

Intervention Type DRUG

Cyclophosphamide

Given intravenously (IV) over 1 hour on consecutive days -3 and -2.

Intervention Type DRUG

Cyclosporine

Patients intolerant to tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment.

Intervention Type DRUG

Decitabine (DAC)

IV over 4 hours on days -8 and -7.

Intervention Type DRUG

Methotrexate

Given intrathecally or intraventricularly monthly, beginning on the second month through the eighth month of treatment.

Intervention Type DRUG

Methylprednisolone

Given according to clinical grade of GVHD procedures.

Intervention Type DRUG

Tacrolimus

IV beginning one day before stem cell infusion, then orally following tolerance to tacrolimus.

Intervention Type DRUG

Allogeneic Bone Marrow Transplantation

Infusion of stem cells on Day 0.

Intervention Type PROCEDURE

Peripheral Blood Stem Cell Transplantation

Stem cell infusion on Day 0.

Intervention Type PROCEDURE

Other Intervention Names

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C-CSF Neupogen Busulfex Myleran Cytoxan Neosar Sandimmune CYA Cyclosporin A Dacogen Depo-Medrol Medrol Solu-Medrol Prograf ABMT PBSCT

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

15 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sergio Giralt, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

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University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MDA-DM-94064

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-G96-0999

Identifier Type: -

Identifier Source: secondary_id

CDR0000065033

Identifier Type: REGISTRY

Identifier Source: secondary_id

DM94-064

Identifier Type: -

Identifier Source: org_study_id

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