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Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders

ConditionsSevere Sickle Cell DiseaseBone Marrow Failure SyndromesMetabolic DisordersImmunologic DisordersHemoglobinopathiesNon-malignant Disorders
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age1-21
SponsorWashington University School of Medicine

About this trial

This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy

Overt or silent stroke or persistently elevated transcranial doppler velocities despite transfusion therapy

Recurrent acute chest syndrome with significant respiratory compromise each time

Sickle nephropathy

Disqualifiers

Patients who have an HLA-identical sibling who is able and willing to donate bone marrow

Patients with cirrhosis or established bridging fibrosis of the liver or active hepatitis

Uncontrolled bacterial, viral, or fungal infection within 6 weeks prior to enrollment

Evidence of HIV infection or known HIV positive serology

Trial design

Design model

Single group

Treatments tested in this trial

  • RIC regimen

    Drug

    Days -60 to -21: hydroxyurea (30mg/kg/day po) \>6hrs prior to 1st dose: alemtuzumab (3mg IV) Day -21: alemtuzumab (10mg IV or S/C) Day -20: alemtuzumab (15mg IV or S/C) (10mg if \< 10kg) Day -19: alemtuzumab (20mg IV or S/C) (10mg if \< 10kg) Days -8 to -4: fludarabine (30mg/m2/day IV) Day -4: thiotepa (8mg/kg IV) Day -3: melphalan (140mg/m2) Days -2 to -1: rest days/no therapy Day 0: bone marrow transplant

  • GVHD prophylaxis regimen

    Drug

    Day +3 to +4: cyclophosphamide (50mg/kg/day IV) Day +5: Start of tacrolimus \& Start of mycophenolate mofetil (MMF) Days +5, +14, +30, +60, +90: abatacept (IND) (10mg/kg/day IV) Day +90: rituximab (375mg/m2 IV once) Patients \>/= 12 yrs - Days +120 to +180: abatacept (IND) monthly (10mg/kg/day IV) Patients \>/= 12 yrs - Days +210 to +390: abatacept (IND) monthly (5mg/kg/day) Patients \<12 yrs - Days +120 to +390: abatacept (IND) monthly (5mg/kg/day IV)

Treatment groups

29 Participants
are divided into 1 treatment group
Group A: RIC Prep Regimen & GVHD ProphylaxisExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Donor engraftment

as measured by chimerism

Time frame
100 days and 1 year post-transplant

Secondary outcomes

1

Time to neutrophil engraftment

as measured by complete blood counts

Time frame
100 days post-transplant
2

Time to platelet engraftment

as measured by complete blood counts

Time frame
100 days post-transplant
3

Effect of BMT on pulmonary function

as measured by pulmonary function tests

Time frame
90 days, 1 year, and 2 years post-transplant
4

Effect of BMT on hepatic function

as measured by laboratory evaluations

Time frame
90 days, 180 days, 1 year, and 2 years post-transplant

Other outcomes

Sponsors and contacts

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

Washington University School of Medicine

Lead sponsor

Source ClinicalTrials.gov
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