Donor stem cell transplant for high-risk hemoglobinopathies and transfusion-dependent red cell disorders

• Alemtuzumab

  Intervention · DRUG

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

• Total Body Irradiation

  Intervention · RADIATION

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

• Cell Infusion

  Intervention · BIOLOGICAL

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

• Thymoglobulin

  Intervention · DRUG

  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.

• Fludarabine

  Intervention · DRUG

  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).

• Busulfan

  Intervention · DRUG

  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.

• Cyclophosphamide

  Intervention · DRUG

  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.

• Sirolimus

  Intervention · DRUG

  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.

• Tacrolimus

  Intervention · DRUG

  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.

• Mycophenolate Mofetil

  Intervention · DRUG

  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.

• Plerixafor (mozobil)

  Intervention · DRUG

  Plerixafor will beused to significantly increase stem cell yields on a second collection day compared to donors who continued mobilization on G-CSF only.

Official title

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

Sponsor

Masonic Cancer Center, University of Minnesota

Conditions

Graft Failure · Sickle Cell Disease · Hemoglobinopathies

Enrolling

62 people

Starts

2024-11-19

Est. completion

2032-06-01

Design

Open-label, non-randomized, parallel groups, Phase 2

Record

View on ClinicalTrials.gov ↗

The sponsor hasn't published answers to common questions for this trial.