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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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.
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Decrease of incidence of HCT failure to less than 20% [ Time Frame: At 200 days ]

HCT failure will be defined as graft rejection (defined as < 5% donor T-cell chimerism) or disease progression within 200 days of transplant. 80% confidence intervals will be used.


Original Primary Outcome:

  • Efficacy of low-dose total-body irradiation in terms of graft rejection rate and disease progression at 200 days
  • Safety


Current Secondary Outcome:

  • Incidence of infections [ Time Frame: 5 years ]
  • Kinetics of donor engraftment in peripheral blood and whole bone marrow [ Time Frame: 1 year post-transplant ]
    Assessed by mixed or full donor chimerism. Mixed chimerism will be defined as the detection of donor T-cells (CD3+) and granulocytes (CD 33+), as a proportion of the total T-cell and granulocyte population, respectively, of greater than 5% and less than 95% in the peripheral blood. Full donor chimerism is defined as >= 95% donor CD3+ T-cells.
  • Probability of progression-free survival in patients with MPD or MDS-RA and those with CMML or MDS-RAEB [ Time Frame: 5 years ]
    80% confidence intervals will be used.
  • Rate of relapse/progression in patients with MPD or MDS-RA and those with CMML or MDS-RAEB [ Time Frame: 5 years ]
    Evidence of disease progression will be an indication for therapeutic intervention. Defined as any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of an incremental increase in 5% blasts in MDS/CMML; defined as any evidence of blastic transformation in agnogenic myeloid metaplasia/atypical CML; and defined as progressive erythrocytosis, thrombocytosis, or evidence of leukemic transformation in polycythemia vera and essential thrombocythemia. 80% confidence intervals will be used.


Original Secondary Outcome:

  • Rate of relapse or progression
  • Probability of progression-free survival
  • Kinetics of donor engraftment
  • Incidence of infections


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: November 9, 2006
Date Started: January 2006
Date Completion:
Last Updated: March 6, 2017
Last Verified: November 2016