NCT00919503

Treosulfan and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders

Allogeneic Hematopoietic Cell Transplantation for Patients With Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 98 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 49 Years
• Healthy volunteers: Not accepted

Summary

This phase II clinical trial studies how well treosulfan and fludarabine phosphate with or without low dose radiation before donor stem cell transplantation works in treating patients with nonmalignant (noncancerous) diseases. Hematopoietic cell transplantation has been shown to be curative for many patients with nonmalignant (noncancerous) diseases such as primary immunodeficiency disorders, bone marrow failure syndromes, hemoglobinopathies, and inborn errors of metabolism (metabolic disorders). Powerful chemotherapy drugs and/or radiation are often used to condition the patient before infusion of the new healthy donor cells. The purpose of the conditioning therapy is to destroy the patient's abnormal bone marrow which doesn't work properly in order to make way for the new healthy donor cells which functions normally. Although effective in curing the patient's disease, many hematopoietic cell transplantation regimens use intensive chemotherapy and/or radiation which can be quite toxic, have significant side effects, and can potentially be life-threatening. Investigators are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan and fludarabine phosphate) with or without low dose radiation results in new blood-forming cells (engraftment) of the new donor cells without increased toxicities in patients with nonmalignant (noncancerous) diseases.

Detailed description

OUTLINE: CONDITIONING REGIMEN: Patients receive treosulfan intravenously (IV) over 2 hours on days -6 to -4 and fludarabine phosphate IV over 1 hour on days -6 to -2. Patients receive anti-thymocyte globulin IV over 4-6 hours on days -4 to -2. Patients undergoing umbilical cord blood transplantation will also receive low dose total-body irradiation on day -1. TRANSPLANTATION: Patients receive either bone marrow, peripheral blood stem cells (PBSC), or umbilical cord blood (UCB) from the donor on day 0. The use of either bone marrow, PBSC, or umbilical cord blood will depend on the donor status. IMMUNOSUPPRESSION: Patients receive a combination of immunosuppressive medications to try and prevent graft-versus-host disease. There are 2 regimens depending on the donor. Regimen A: Patients undergoing bone marrow or PBSC transplantation receive tacrolimus daily from day -1 to 50 followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Regimen B: Patients undergoing UCB transplantation receive cyclosporine on days -3 to 100 followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil on days 0 to 40 followed by a taper until day 96 in the absence of GVHD. After completion of study treatment, patients are followed up periodically for 5 years.

Conditions

• Non-Neoplastic Hematologic and Lymphocytic Disorder

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Bone Marrow Transplantation	Infused IV
BIOLOGICAL	Anti-Thymocyte Globulin	Given IV
DRUG	Cyclosporine	Given IV or PO
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Methotrexate	Given IV
DRUG	Mycophenolate Mofetil	Given IV or PO
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Infused IV
DRUG	Tacrolimus	Given IV or PO
RADIATION	Total-Body Irradiation	Undergo total body irradiation
DRUG	Treosulfan	Given IV
PROCEDURE	Umbilical Cord Blood Transplantation	Single or double unit umbilical cord blood transplant, infused IV

Timeline

• Start date: 2009-07-31
• Primary completion: 2020-06-10
• Completion: 2020-06-10
• First posted: 2009-06-12
• Last updated: 2021-08-13
• Results posted: 2021-08-13

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study