Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders

Chronic Myelomonocytic Leukemia Clinical Trial

Official title: Low-Dose TBI Dose Escalation to Decrease Risks of Progression and Graft Rejection After Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning as Treatment for Untreated Myelodysplastic Syndrome or Myeloproliferative Disorders - A Multi-Center Trial

Status Completed

Clinical Trial Summary

This phase II trial studies the side effects and best dose of total-body irradiation when given together with fludarabine phosphate followed by a donor peripheral stem cell transplant in treating patients with myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD). Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Decrease the incidence of day-200 hematopoietic cell transplantation (HCT) failure to < 20% in patients with MDS-Refractory anemia (RA)-(ringed sideroblasts [RS])/MPD and in patients with chronic myelomonocytic leukemia (CMML)/refractory anemia with excess blasts (RAEB).

SECONDARY OBJECTIVES:

I. The rate of relapse/progression in patients with MPD or MDS-RA and those with CMML or MDS-RAEB.

II. The probability of progression free survival (PFS) in patients with MPD or MDS-RA and those with CMML or MDS-RAEB.

III. The kinetics of donor engraftment.

IV. The incidence of infections.

OUTLINE: This is a dose-escalation study of total body irradiation (TBI).

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.

PERIPHERAL BLOOD STEM CELL (PBSC) TRANSPLANTATION: Patients undergo filgrastim (G-CSF)-mobilized PBSC infusion after TBI on day 0.

IMMUNOSUPPRESSION:

Matched Related Donor: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56, followed by a taper until day 180. Patients also receive mycophenolate mofetil (MMF) PO BID beginning 4-6 hours after transplantation on day 0 and continue until day 27.

Unrelated Donor: Patients receive cyclosporine PO BID on days -3 to 100, followed by a taper until day 180. Patients also receive MMF PO three times daily beginning 4-6 hours after transplantation on day 0 and continue until day 40, followed by a taper until day 96.

After completion of study treatment, patients are followed periodically. ;

Related Conditions & MeSH terms

• Anemia
• Anemia, Refractory, with Excess of Blasts
• Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndrome
• Essential Thrombocythemia
• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Paroxysmal Nocturnal Hemoglobinuria
• Polycythemia
• Polycythemia Vera
• Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
• Preleukemia
• Primary Myelofibrosis
• Refractory Anemia
• Refractory Anemia With Excess Blasts
• Refractory Anemia With Ring Sideroblasts
• Refractory Cytopenia With Multilineage Dysplasia
• Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts
• Syndrome
• Thrombocythemia, Essential
• Thrombocytosis

• NCT number: NCT00397813
• Study type: Interventional
• Source: Fred Hutchinson Cancer Research Center
• Status: Completed
• Phase: Phase 2
• Start date: January 2006
• Completion date: March 2018