Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures

Part of paid clinical trials in Baltimore, Maryland.

Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study ID
NCT04232085
Phase
PHASE2
Status
Recruiting
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Conditions

  • Bone Marrow Failure
  • Dyskeratosis Congenita
  • Fanconi Anemia
  • Hoyeraal-Hreidarsson Syndrome
  • Immune Deficiency Disease
  • Non Fanconi DNA-DSB Repair Disorder
  • Primary Immune Deficiency Disorder
  • Short Telomere Length
  • Short Telomere Syndrome
  • Telomere Biology Disorder

Eligibility Criteria

Sex
ALL
Age
4 Months - 50 Years
Healthy Volunteers
Not accepted

Interventions

  • Alemtuzumab — DRUG
    Preparative regimen
  • Fludarabine — DRUG
    Preparative regimen
  • Melphalan — DRUG
    Preparative regimen
  • Low Dose Total Body Irradiation — RADIATION
    Preparative regimen
  • Cyclophosphamide — DRUG
    GVHD prophylaxis
  • Tacrolimus — DRUG
    GVHD prophylaxis
  • Mycophenolate Mofetil — DRUG
    GVHD prophylaxis

Study Details

Phase II prospective trial to assess the rates of donor engraftment using reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) and post-transplant cyclophosphamide (PTCy) for patients with primary immune deficiencies (PID), immune dysregulatory syndromes (IDS), inherited bone marrow failure syndromes (IBMFS), short telomere syndromes, Fanconi anemia, and non-Fanconi DNA double-strand break (DNA-dsb) repair disorder.

Key Dates

Start date
Feb 12, 2020
Status verified
Nov 2025
Primary completion
Dec 31, 2027
Completion
Dec 31, 2028

Study Design

Enrollment
27 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: PID/IDS/IBMFS
    Alemtuzumab IV infusion over 2 hours on days -14, -13, and -12. Day -14 3 mg followed by 10 mg. Day -13 15 mg (or 10 mg if \<10 kg). Day -12 20 mg (or 10 mg if \<10 kg). Fludarabine 30 mg/m2/day IV infusion over 2 hours on days -6 to -2. Melphalan 70 mg/m2/day IV infusion over 30-60 minutes on days -3 and -2. (Or may be given as a single infusion of 140 mg/m2/day on day -2.) Total body irradiation (PID/IDS): 200 cGy will be administered in a single fraction on day -1. Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Tacrolimus begins on day 5, at least 24 hours after completion of posttransplantation Cy at 0.015mg/kg IBW/dose IV over 4 hours every 12 hours. Mycophenolic acid mofetil (MMF) begins on day 5 at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).
  • Experimental: Short Telomere Syndrome
    Alemtuzumab IV infusion over 2 hours on days -14, -13, and -12. Day -14 3 mg followed by 10 mg. Day -13 15 mg (or 10 mg if \<10 kg). Day -12 20 mg (or 10 mg if \<10 kg). Fludarabine 30 mg/m2/day IV infusion over 2 hours on days -6 to -2. TBI 200 cGY day -1 Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 25-50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Starting dose for haplo/MMUD= 50 mg/kg; starting dose for HLA matched= 25 mg/kg Tacrolimus begins on day 5, at least 24 hours after completion of post transplantation Cy at 0.015mg/kg IBW/dose IV over 4 hours every 12 hours. Mycophenolic acid mofetil (MMF) begins on day 5 at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).
  • Experimental: Fanconi Anemia or DNA-dsb repair
    Alemtuzumab IV infusion over 2 hours on days -14, -13, and -12. Day -14 3 mg followed by 10 mg. Day -13 15 mg (or 10 mg if \<10 kg). Day -12 20 mg (or 10 mg if \<10 kg). Fludarabine 30 mg/m2/day IV infusion over 2 hours on days -6 to -2. TBI 200 cGY day -1 Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 25 mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Tacrolimus begins on day 5, at least 24 hours after completion of post transplantation Cy at 0.015mg/kg IBW/dose IV over 4 hours every 12 hours. Mycophenolic acid mofetil (MMF) begins on day 5 at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).

Primary Outcome Measure

Donor Engraftment [ Time Frame: 60 Days ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Johns Hopkins UniversityBaltimoreMaryland21287
Megan Petrycki, MSN, RN
[email protected]
Heather J Symons, MD (PRINCIPAL_INVESTIGATOR)

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By research site
Johns Hopkins University· Baltimore, MD

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