Allo HSCT for High Risk Hemoglobinopathies

NCT06872333 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2024LS140
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Graft versus Host Disease (GvHD)

  1 year

Secondary Outcomes (4)

• Overall Survival

  1 and 2 years

• Grade 3-4 Acute GvHD

  2 years

• Chronic Graft versus Host Disease (GvHD) Free

  2 years

• Failure Free Survival

  2 years

Study Arms (4)

Arm A

EXPERIMENTAL

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

Drug: Alemtuzumab; Radiation: Total Body Irradiation; Biological: Cell Infusion; Drug: Sirolimus; Drug: Mycophenolate Mofetil

Arm B

EXPERIMENTAL

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

Biological: Cell Infusion; Drug: Thymoglobulin; Drug: Fludarabine; Drug: Busulfan; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Arm C

EXPERIMENTAL

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

Biological: Cell Infusion; Drug: Thymoglobulin; Drug: Fludarabine; Drug: Busulfan; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Arm D

EXPERIMENTAL

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

Radiation: Total Body Irradiation; Biological: Cell Infusion; Drug: Thymoglobulin; Drug: Fludarabine; Drug: Thiotepa; Drug: Cyclophosphamide; Drug: Sirolimus; Drug: Mycophenolate Mofetil

Interventions

Alemtuzumab DRUG

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

Also known as: Campath

Arm A

Total Body Irradiation RADIATION

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

Also known as: TBI

Arm A; Arm D

Cell Infusion BIOLOGICAL

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

Arm A; Arm B; Arm C; Arm D

Thymoglobulin 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.

Also known as: Rabbit ATG

Arm B; Arm C; Arm D

Fludarabine 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).

Arm B; Arm C; Arm D

Busulfan 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.

Arm B; Arm C

Thiotepa DRUG

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

Arm D

Cyclophosphamide 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.

Also known as: Cyclophosphamide with MESNA

Arm D

Sirolimus 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.

Arm A; Arm D

Tacrolimus 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.

Arm B; Arm C

Mycophenolate Mofetil 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.

Also known as: (MMF)

Arm A; Arm B; Arm C; Arm D

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; Hemoglobinopathies

Interventions

Alemtuzumab; Whole-Body Irradiation; Insulin Infusion Systems; thymoglobulin; fludarabine; Busulfan; Thiotepa; Cyclophosphamide; Mesna; Sirolimus; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques; Drug Delivery Systems; Drug Therapy; Infusion Pumps; Equipment and Supplies; Artificial Organs; Surgical Equipment; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Sulfhydryl Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Central Study Contacts

Ashish Gupta, MBBS, MPH

CONTACT

612-626-2961; gupta461@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 12, 2025
• Study Start: November 19, 2024
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2032
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (1)