Clinical Trial: Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Treosulfan Based Preparative Regimen

Brief Summary: This phase II trial studies how well giving treosulfan together with fludarabine phosphate and total-body irradiation (TBI) works in treating patients with hematological cancer who are undergoing umbilical cord blood transplant (UCBT). Giving chemotherapy, such as treosulfan and fludarabine phosphate, and TBI before a donor UCBT helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related or unrelated donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. 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. Graft failure/rejection and secondary graft failure.

II. Day -200 non-relapse mortality.

SECONDARY OBJECTIVES:

I. Platelet engraftment by six months.

II. Grade II-IV and III-IV acute graft-versus-host disease (GVHD) at day 100 and one year.

III. Chronic GVHD.

IV. Clinically significant infections.

V. Overall survival.

VI. Relapse or disease progression.

VII. Immune reconstitution (Fred Hutchinson Cancer Research Center [FHCRC] only).

VIII. Emergence of a dominant unit (FHCRC only).

OUTLINE:

ARM I (low risk for graft failure): Patients receive a conditioning regimen comprising fludarabine phosphate intravenously (IV) over 1 hour once daily (QD) on days -6 to -2 and treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV or orally (PO) 2-3 times daily on days -3 to 100, followed by a taper in the absence of GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed by a taper in the absence of GVHD.

ARM II (high risk for graft failure): Patients receive a conditioning regimen, TBI, donor UCBT, GVHD prophylaxis, and mycophenolate mofetil as in Arm I.

Current Primary Outcome:

• Incidence of graft failure/rejection [ Time Frame: Up to 2 years ]
• Incidence of non-relapse mortality [ Time Frame: At day -200 ]
• Incidence of secondary graft failure [ Time Frame: At day 55 ]

Original Primary Outcome:

• Combined incidence of primary graft failure/rejection and secondary graft failure
• Non-relapse mortality at day 200

Current Secondary Outcome:

• Incidence of acute GVHD [ Time Frame: Day 100 ]
  Determined based on the organ stage, response to treatment and whether GVHD was a major cause of death.
• Incidence of acute or chronic GVHD [ Time Frame: At 1 year ]
  Overall GVHD is determined based on the organ stage, response to treatment and whether GVHD was a major cause of death. Chronic GVHD will be defined according to the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Described as mild, moderate, or severe as graded according to the attached Organ Scoring Sheet. Symptoms consistent with both chronic and acute GVHD occurring after day 100 will be considered overlap chronic GVHD syndrome.
• Incidence of clinically significant infections [ Time Frame: At 6 months ]
  Collected and graded according to the modified National Cancer Institute Common Toxicity Criteria.
• Incidence of platelet engraftment [ Time Frame: At 6 months ]
• Incidence of relapse or disease progression [ Time Frame: Up to 2 years ]
• Non-relapse mortality [ Time Frame: Up to 2 years ]
  Summarized using Kaplan-Meier and cumulative incidence estimates.
• One year survival [ Time Frame: At 1 year ]
  Summarized using Kaplan-Meier and cumulative incidence estimates.
• Overall survival [ Time Frame: Up to 2 years ]
  Summarized using Kaplan-Meier and cumulative incidence estimates.
• Progression-free survival [ Time Frame: Up to 2 years ]
  Summarized using Kaplan-Meier and cumulative incidence estimates.

Original Secondary Outcome:

• 1-year survival
• Overall survival
• Incidence of platelet engraftment at 6 months
• Incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) at day 100 and 1 year
• Incidence of chronic GVHD at 1 year
• Incidence of clinically significant infections at 6 months, 1 year, and 2 years
• Progression-free survival
• Relapse

Dates:
Date Received: November 21, 2008
Date Started: October 2008
Date Completion:
Last Updated: December 16, 2016
Last Verified: December 2016