NCT03128996

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at P25-P50 for phase_1

Timeline
83mo left

Started Mar 2017

Longer than P75 for phase_1

Geographic Reach
1 country

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress58%
Mar 2017Apr 2033

Study Start

First participant enrolled

March 20, 2017

Completed
14 days until next milestone

First Submitted

Initial submission to the registry

April 3, 2017

Completed
23 days until next milestone

First Posted

Study publicly available on registry

April 26, 2017

Completed
10.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2028

Expected
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2033

Last Updated

May 29, 2026

Status Verified

May 1, 2026

Enrollment Period

11 years

First QC Date

April 3, 2017

Last Update Submit

May 26, 2026

Conditions

Severe Sickle Cell DiseaseBone Marrow Failure SyndromesMetabolic DisordersImmunologic DisordersHemoglobinopathiesNon-malignant Disorders

Keywords

Bone marrow transplantTransplantTransplantationReduced IntensityFamilial HLA mismatched

Outcome Measures

Primary Outcomes (1)

  • Donor engraftment

    as measured by chimerism

    100 days and 1 year post-transplant

Secondary Outcomes (12)

  • Time to neutrophil engraftment

    100 days post-transplant

  • Time to platelet engraftment

    100 days post-transplant

  • Effect of BMT on pulmonary function

    90 days, 1 year, and 2 years post-transplant

  • Effect of BMT on hepatic function

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

  • Effect of BMT on neurologic function

    90 days, 1 year, and 2 years post-transplant

  • +7 more secondary outcomes

Study Arms (1)

RIC Prep Regimen & GVHD Prophylaxis

EXPERIMENTAL

Single arm study. All patients receive the same Reduced Intensity Conditioning (RIC) regimen and GVHD prophylaxis regimen

Drug: RIC regimenDrug: GVHD prophylaxis regimen

Interventions

RIC regimenDRUG

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

Also known as: Transplant Preparative Regimen, Transplant Conditioning Regimen
RIC Prep Regimen & GVHD Prophylaxis
GVHD prophylaxis regimenDRUG

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)

Also known as: Graft versus Host Disease prophylaxis regimen
RIC Prep Regimen & GVHD Prophylaxis

Eligibility Criteria

Age1 Day - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy
  • For patients with sickle cell disease, must have one of the following severe manifestations:
  • 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
  • Recurrent admissions for vaso-occlusive episodes resulting in prolonged opioid use and poor quality of life with interrupted school attendance activity
  • Red cell alloimmunization with the need for chronic transfusions
  • Recurrent osteonecrosis or multiple joint involvement from avascular necrosis
  • Patients with sickle cell disease must have hemoglobin S \< 30% within 30 days prior to beginning alemtuzumab
  • Age \</= 20.99 years at the time of enrollment
  • Performance score \>/= 50
  • Left ventricular ejection fraction \> 40% or left ventricular shortening fraction \> 26% by echocardiogram
  • DLCO \> 40% (corrected for hemoglobin) or pulse oximetry with a baseline O2 saturation of \>/= 90% on room air if too young to perform PFTs
  • Serum creatinine \</= 1.5x upper limit of normal for age and/or GFR \> 70 mL/min/1.73m2
  • Direct bilirubin \< 2x upper limit of normal for age
  • +5 more criteria

You may not qualify if:

  • 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
  • Patients who have received a previous stem cell transplant
  • Patients who have received an investigational drug or device or off-label use of a drug or device within 3 months of enrollment
  • Females who are pregnant or breast feeding
  • Patients with active autoimmune disease (e.g. sarcoidosis, lupus, scleroderma)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Yale School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

Nemours Children's Health

Wilmington, Delaware, 19803, United States

RECRUITING

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (1)

  • Ngwube A, Shah N, Godder K, Jacobsohn D, Hulbert ML, Shenoy S. Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease. Blood Adv. 2020 Aug 25;4(16):3894-3899. doi: 10.1182/bloodadvances.2020002236.

    PMID: 32813873DERIVED

MeSH Terms

Conditions

Anemia, Sickle CellBone Marrow Failure DisordersMetabolic DiseasesImmune System DiseasesHemoglobinopathies

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesBone Marrow DiseasesNutritional and Metabolic Diseases

Study Officials

  • Shalini Shenoy, MD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Shalini Shenoy, MD

CONTACT

314-454-6018shalinishenoy@wustl.edu

Ian Snyder, BS, CCRP

CONTACT

314-273-5953ian.s@wustl.edu

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 3, 2017

First Posted

April 26, 2017

Study Start

March 20, 2017

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2033

Last Updated

May 29, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will not share

Locations

US(4)