Recruiting
Phase 2

HSCT

Sponsor:

Masonic Cancer Center, University of Minnesota

Code:

NCT06872333

Conditions

Graft Failure

Sickle Cell Disease

Hemoglobinopathies

Eligibility Criteria

Sex: All

Age: 0 - 55

Healthy Volunteers: Accepted

Interventions

Alemtuzumab

Total Body Irradiation

Cell Infusion

Thymoglobulin

Fludarabine

Study Details

Brief summary:

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.

Conditions

Graft Failure

Sickle Cell Disease

Hemoglobinopathies

Study ID

NCT06872333

Start date

Nov 19, 2024

Status verified date

Jun, 2026

Completion date

Jun 1, 2032

Anticipated

Primary completion date

Jun 1, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 55

Healthy Volunteers: Accepted

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 30 days of the start of treatment
  • HIV infection with a detectable viral load. All HIV+ patients must be evaluated by infectious disease (ID) and an HIV management plan established prior to transplantation.
  • 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

Study Design

Enrollment

62 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Arm A - Closed

Arm A Matched sib regimen - Age 6 -55 (per physician preference for patients over 6) Campath/TBI

experimental: Arm B

Arm B Matched sib regimen - 0-55 (per physician preference for patients over 6) ATG/Flu/Bu

experimental: Arm C

Arm C Fully Matched unrelated donor (MUD)- - 0-55 years; ATG/Flu/Bu

experimental: Arm D

Arm D: Haploindentical or mismatched unrelated donors (MMUD) - 0-55 years; ATG/Thiotepa/Cyclophosphamide/MESNA/Flu/TBI

experimental: Arm E

Matched sib regimen - Age 6-55 (per physician preference for patients over 6) Campath/TBI with peripheral blood stem cell graft

Interventions

Alemtuzumab

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

Total Body Irradiation

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

Cell Infusion

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

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.

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).

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.

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.

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.

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.

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.

Plerixafor (mozobil)

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

Primary outcome measure

  • Incidence of Graft versus Host Disease (GvHD) [ Time Frame: 1 year ]

Central Contacts and Locations

Central contacts

Ashish Gupta, MBBS, MPH

612-626-2961gupta461@umn.edu

Locations

Masonic Cancer Center

Recruiting

Minneapolis, Minnesota, United States, 55455

More Information

Sponsor

Masonic Cancer Center, University of Minnesota

Last update posted

Jun 4, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Masonic Cancer Center, University of Minnesota on 2026-06-04.