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

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 2

Conditions: Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes

Treatments: Drug: Cladribine; Drug: Cytarabine (Ara-C); Drug: Fludarabine Phosphate; Biological: Filgrastim; Drug: Methylprednisolone; Drug: Cyclosporine; Drug: Idarubicin; Procedure: Peripheral Blood Stem Cell Transplantation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00002833

P30CA016672 (U.S. NIH Grant/Contract)

CDR0000065035 (Registry Identifier)

NCI-G96-1001

MDA-DM-94078 (Other Identifier)

DM94-078

Details and patient eligibility

About

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. Colony stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation plus filgrastim in treating patients who have acute or chronic myelogenous leukemia.

Full description

OBJECTIVES: I. Determine the toxic effects and feasibility of using filgrastim in promoting hematopoietic recovery and leukemia control after intensive but nonmyeloablative salvage chemotherapy. II. Determine the engraftment kinetics and degree of chimerism achievable.

OUTLINE: The trial will have 2 patient groups. Patients not in remission are assigned to group 1, while patients in remission are assigned to group 2. Then, groups are divided into 2 treatment arms. Patients failing fludarabine therapy receive cytarabine (Ara-C) IV over 2 hours on days -7, -6, -5, -4 and -3. Beginning 4 hours before the first dose of Ara-C, patients receive cladribine (2-chlorodeoxyadenosine; 2-CdA) by continuous infusion for 5 days. Patients without prior fludarabine therapy receive fludarabine IV over 30 minutes daily on days -6, -5, -4 and -3. Ara-C IV begins 4 hours after the beginning of the fludarabine infusion and continues for 4 hours. Idarubicin IV is given on days -6, -5 and -4. Donors receive filgrastim SC every 12 hours for 2 days prior to stem cell collection. Cells are infused on day 0. For GVHD prophylaxis, all patients receive cyclosporine via continuous IV infusion. Oral cyclosporine is administered once patients tolerate oral feeding and continued for 6 months postinfusion. Then, the dose of cyclosporine is tapered 10% weekly until discontinued. Methylprednisolone begins 5 days after infusion and is gradually tapered.

PROJECTED ACCRUAL: A maximum of 15 patients per arm are likely to be entered in 24 to 36 months.

Enrollment: 53 patients

Sex: All

Ages: 55 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS: Acute leukemia with poor risk cytogenetic features (-5,-7, +8) in first complete remission Poor risk myelodysplasia Refractory anemia with excess blasts (RAEB) RAEB in transformation (RAEB-T) Chronic myelomonocytic leukemia (CMML) Chronic myelogenous leukemia (CML) in late chronic phase Acute leukemia with greater than first complete remission or transformed CML or CMML

PATIENT CHARACTERISTICS: Age: 55 to 65 65 to 70 (at the discretion of study chairperson on basis of performance status) 55 and under (if declined for conventional high dose chemotherapy due to concurrent medical conditions (i.e. ejection fraction less than 50, FEV1, FVC, or DLCO less than 50%, abnormal LFTs) Performance status: Zubrod less than 2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 3 mg/dL Renal: Serum creatinine less than 2 mg/dL Cardiovascular: Ejection fraction greater than 40% per MUGA scan Pulmonary: Not specified Other: No active uncontrolled infection HLA compatible donor capable of donating stem cells via apheresis

PRIOR CONCURRENT THERAPY: Not specified

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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53 participants in 2 patient groups

Group 1A

Experimental group

Description:

Group 1A - With or Without Remission + Failing Fludarabine therapy: Ara-C IV over 2 hours on days -7, -6, -5, -4 and -3 with Cladribine continuous infusion for 5 days, beginning 4 hours before Ara-C first dose. Idarubicin IV Days -6, -5 and -4. Cells infused on day 0. Cyclosporine via continuous IV infusion, oral cyclosporine administered for 6 months postinfusion (tapered 10% weekly until discontinued). Methylprednisolone begins 5 days after infusion then gradually tapered.

Treatment:

Procedure: Peripheral Blood Stem Cell Transplantation

Drug: Idarubicin

Drug: Cyclosporine

Drug: Methylprednisolone

Biological: Filgrastim

Drug: Cytarabine (Ara-C)

Drug: Cladribine

Group 1B

Experimental group

Description:

Group 1B: With or Without Remission, No previous Fludara Therapy Fludarabine IV over 30 minutes daily on days -6, -5, -4 and -3. Ara-C IV begins 4 hours after fludarabine infusion, continues for 4 hours. Idarubicin IV Days -6, -5 and -4. Cells infused on day 0. Cyclosporine via continuous IV infusion, oral cyclosporine administered for 6 months postinfusion (tapered 10% weekly until discontinued). Methylprednisolone begins 5 days after infusion then gradually tapered.

Treatment:

Procedure: Peripheral Blood Stem Cell Transplantation

Drug: Idarubicin

Drug: Cyclosporine

Drug: Methylprednisolone

Drug: Fludarabine Phosphate

Biological: Filgrastim

Drug: Cytarabine (Ara-C)