RECRUITINGPhase 2INTERVENTIONAL

Allo HSCT for High Risk Hemoglobinopathies

Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent Disorders

About This Trial

A single center, open label, interventional, phase II trial for donor transplant for high risk hemoglobinopathies and other red cell transfusion dependent disorders utilizing allogeneic hematopoietic stem cell transplantation (HSCT) regimens.

Who May Be Eligible (Plain English)

Who May Qualify: - Sickle Cell Disease (SCD) - SCD Patients with a fully matched sibling donor (MSD) irrespective of the frequency or severity of symptoms MSD transplant can be considered. Parents/patient must be counseled as to the risks and benefits and provide their voluntary willing to sign a consent form - Transfusion Dependent Alpha- or Beta- Thalassemia - Diamond Blackfan Anemia - Other Non-Malignant Hematologic Disorders - Karnofsky ≥ 60%, Lansky play score ≥ 60. Patients with lower performance score can be considered based on study team's evaluation. - Sexually active persons of childbearing potential or persons with partners of childbearing potential must agree to use a highly effective form of contraception during study treatment and for at least 4 months after the transplant. Who Should NOT Join This Trial: - Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment - HIV Positive - Active, uncontrolled infection - infection that is stable or improving after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections) will be permitted - Known allergy to any of the study components - Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements - Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Sickle Cell Disease (SCD) * SCD Patients with a fully matched sibling donor (MSD) irrespective of the frequency or severity of symptoms MSD transplant can be considered. Parents/patient must be counseled as to the risks and benefits and provide their voluntary informed consent * Transfusion Dependent Alpha- or Beta- Thalassemia * Diamond Blackfan Anemia * Other Non-Malignant Hematologic Disorders * Karnofsky ≥ 60%, Lansky play score ≥ 60. Patients with lower performance score can be considered based on study team's evaluation. * Sexually active persons of childbearing potential or persons with partners of childbearing potential must agree to use a highly effective form of contraception during study treatment and for at least 4 months after the transplant. Exclusion Criteria: * Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment * HIV Positive * Active, uncontrolled infection - infection that is stable or improving after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections) will be permitted * Known allergy to any of the study components * Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements * Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study

Treatments Being Tested

DRUG

Alemtuzumab

Alemtuzumab (Campath) will be administered IV over 2 hours on day -8 to day -4.

RADIATION

Total Body Irradiation

400 cGy in 2 split fractions will be administered per Department of RadiationOncology SOPs.

BIOLOGICAL

Cell Infusion

On day 0 the cells will be infused per cell source specific institutional guidelines

DRUG

Thymoglobulin

ATG will be administered IV every 24 hours beginning on day -8 for all patients. Dosing will be model-based using Bayesian methodology13,14,15. Total doses and total number of doses (1-4 doses) will be determined based on absolute lymphocyte count and weight.

DRUG

Fludarabine

Fludarabine will be administered IV over 1 hour every 24 hours on day -5 to day - 2. The daily dose of fludarabine will be determined by model-based dosing utilizing Bayesian methodology with a cumulative area under the curve (cAUC) of 20 mg\*hr/L (range 18-22 mg\*hr/L).

DRUG

Busulfan

Busulfan dosing and administration and therapeutic drug monitoring (TDM) per institutional guidelines. Initial busulfan dosing will be determined by model-based dosing utilizing Bayesian methods with a cumulative area under the curve (cAUC) of 75 mg\*hr/L.

DRUG

Thiotepa

Thiotepa will be administered at a dose 5 mg/kg IV every 12 hours on day - 7 over 2 hours. Patients will undergo thiotepa skin care per institutional guidelines

DRUG

Cyclophosphamide

Cyclophosphamide will be administered at a dose of 14.5 mg/kg over 2 hours IV daily on days -6 and -5. Cyclophosphamide dosing is calculated based on actual body weight (ABW). For Arm D - Cyclophosphamide 50 mg/kg IV will be administered over 2 hours on days +3 and +4. Cyclophosphamide dosing for post-transplant is calculated based on ideal body weight (IBW) unless patient weighs less than IBW, in which case actual body weight (ABW) will be used.

DRUG

Sirolimus

Patients on Arm A and Arm D will receive sirolimus; beginning on day -3 and continuing until day +180 for patients on Arm A or beginning on day +5 and continuing until 1 year post transplant for patients on Arm D.

DRUG

Tacrolimus

Patients on Arm B and Arm C will receive tacrolimus, beginning on day -3 and continuing until day +180. Tacrolimus dosing and monitoring will be per institutional guidelines.

DRUG

Mycophenolate Mofetil

MMF will begin on day -3 (Arm A, B \& C) or day +5 (Arm D). Patients treated on adult service will receive 15 mg/kg (max 1500 mg/dose) given every 12 hours, rounded to nearest 250 mg. Patients on pediatric service will receive 15 mg/kg (max 1000 mg/dose) given every 8 hours. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. MMF will be stopped at day +30 (Arms A, B \& C) or day +35 (Arm D) or 7 days after engraftment, whichever day is later, if no acute GVHD.

Locations (1)

Masonic Cancer Center

Minneapolis, Minnesota, United States