Health TrialsbyHealthPanel

Allo HSCT for High Risk Hemoglobinopathies

ConditionsGraft FailureSickle Cell DiseaseHemoglobinopathies
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeUp to 55
SponsorMasonic Cancer Center, University of Minnesota

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Alemtuzumab

    Drug

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

  • Total Body Irradiation

    Radiation

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

  • Cell Infusion

    Biological/Vaccine

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

  • 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.

  • 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).

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • Plerixafor (mozobil)

    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.

Treatment groups

62 Participants
are divided into 5 treatment groups
Group A: Arm A - ClosedExperimental treatment 5 interventions
Group B: Arm BExperimental treatment 6 interventions
Group C: Arm CExperimental treatment 7 interventions
Group D: Arm DExperimental treatment 3 interventions
Group E: Arm EExperimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

Incidence of Graft versus Host Disease (GvHD)

Time frame
1 year

Secondary outcomes

1

Overall Survival

Overall survival post HCT

Time frame
1 and 2 years
2

Grade 3-4 Acute GvHD

Grade 3-4 acute Graft versus Host Disease (GvHD) at 2 years post HCT.

Time frame
2 years
3

Chronic Graft versus Host Disease (GvHD) Free

Chronic Graft versus Host Disease (GvHD) Free at 2 years post HCT.

Time frame
2 years
4

Failure Free Survival

Failure Free Survival 2 years post HCT.

Time frame
2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Masonic Cancer Center, University of Minnesota

Lead sponsor

Source ClinicalTrials.gov
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