Clinical Trial Detail

The purpose of this phase II clinical trial is to see if the combination of two chemotherapy drugs, treosulfan and fludarabine with or without low dose radiation, just prior to stem cell transplantation is safe and effective in 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 at the Fred Hutchinson Cancer Research Center in collaboration with Oregon Health & Sciences University, Vanderbilt University, and Medical College of Wisconsin are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan and fludarabine) with or without low dose radiation results in engraftment of the new donor cells without increased toxicities in patients with nonmalignant (noncancerous) diseases

Ages Eligible for Study: up to 54 Years

Genders Eligible for Study: Both

- Patients with a nonmalignant disease treatable by allogeneic HCT

- Patients with a known nonmalignant disease that is not clearly defined will need to be discussed with the protocol principal investigator (PI) (Dr. Lauri Burroughs) and potentially the nonmalignant board to determine if they are eligible for HCT on this study

- DONOR: Human leukocyte antigens (HLA)-identical related donors or unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 or mismatched for a single allele at HLA-A, B, C, DRB1 or a single DQB1 antigen or allele mismatch by high resolution deoxyribonucleic acid (DNA) typing

- DONOR: Bone marrow is the preferred cell source; PBSC are allowed if donor refuses or is unable to give marrow

- DONOR, Umbilical Cord Blood: Unit selection is based on the cryopreserved total nucleated cell (TNC) dose and matching at HLA-A, B antigen level and DRB1 allele level typing. While HLA-C antigen/allele level typing is not considered in the matching criteria, if available, may be used to optimize unit selection.

- DONOR, Umbilical Cord Blood: The patient and the cord blood unit(s) must be matched for at least 4 of 6 loci as defined above.

- DONOR, Umbilical Cord Blood: Selection of two UCB units is allowed to provide sufficient cell dose

Other eligibility criteria may apply.

- Patients with idiopathic aplastic anemia and Fanconi anemia; (patients with aplastic anemia associated with paroxysmal nocturnal hemoglobinuria [PNH] or inherited marrow failure syndromes, except Fanconi anemia, will be allowed)

- Patients with impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist

- Patients with impaired pulmonary function as evidenced by diffusion capacity of the lung for carbon monoxide (DLCO) < 50% of predicted (or, if unable to perform pulmonary function tests, then oxygen [O2] saturation < 92% on room air)

- Patients with impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2X upper normal limit or dialysis-dependent

- Patients with evidence of synthetic dysfunction or severe cirrhosis requiring deferral of conditioning as recommended by a gastroenterology specialist

- Patients with an active infectious disease requiring deferral of conditioning; as recommended by an infectious disease specialist

- Patients who are seropositive for human immunodeficiency virus (HIV)

- Females who are pregnant or breast-feeding

- Patients with a known hypersensitivity to treosulfan and/or fludarabine

- Receiving another experimental drug within 4 weeks of initiation of conditioning (day -6)

- DONOR: Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis

- DONOR: HIV-positive

- DONOR: With active infectious hepatitis

- DONOR: Females with a positive pregnancy test

Other exclusion criteria may apply.