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

May 26, 2026 updated by: Washington University School of Medicine

A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patients < 21 years of age with a non-malignant disorder benefited by hematopoietic stem cell transplant will receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan.

This will be followed by a familial HLA-mismatched bone marrow transplant. The primary objective is to establish safety and donor cell engraftment at 100 days and 1 year post-transplant.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
29

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Ian Snyder, BS, CCRP
  • Phone Number: 314-273-5953
  • Email: ian.s@wustl.edu

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale School of Medicine
        • Principal Investigator:
          • Lakshmanan Krishnamurti, MD
        • Contact:
          • Lakshmanan Krishnamurti, MD
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Nemours Children's Health
        • Principal Investigator:
          • Emi Caywood, MD
        • Contact:
          • Emi Caywood, MD
          • Phone Number: 800-416-4441
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Helen DeVos Children's Hospital
        • Contact:
          • Troy Quigg, DO
        • Principal Investigator:
          • Troy Quigg, DO
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Shalini Shenoy, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 day to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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:

    1. Overt or silent stroke or persistently elevated transcranial doppler velocities despite transfusion therapy
    2. Recurrent acute chest syndrome with significant respiratory compromise each time
    3. Sickle nephropathy
    4. Recurrent admissions for vaso-occlusive episodes resulting in prolonged opioid use and poor quality of life with interrupted school attendance activity
    5. Red cell alloimmunization with the need for chronic transfusions
    6. 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
  • ALT and AST < 5x upper limit of normal for age

  • Participants who have or are receiving >/= 8 packed red blood cell transfusions for >/= 1 year or >/= 20 packed red blood cell transfusions (lifetime cumulative) will undergo liver MRI for estimation of hepatic iron content.

    1. Liver biopsy is indicated for hepatic iron content >/= 7mg Fe/mg liver dry weight by liver MRI. Histologic examination of the liver must document for the absence of cirrhosis, bridging fibrosis, and active hepatitis

  • Female subjects of childbearing potential, must agree to practice 2 methods of contraception at the same time from the time of signing of informed consent through 12 months post transplant. Male subjects must agree to practice effective barrier contraception or practice true abstinence from the time of signing informed consent through 12 months post transplant.
  • Written informed consent must be obtained from all recipients in accordance with the guidelines of the institution's Human Studies Committee.

Exclusion Criteria:

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: RIC Prep Regimen & GVHD Prophylaxis
Single arm study. All patients receive the same Reduced Intensity Conditioning (RIC) regimen and GVHD prophylaxis regimen
Drug: RIC regimen
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
Other Names:
  • Transplant Preparative Regimen
  • Transplant Conditioning Regimen
Drug: GVHD prophylaxis regimen
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)
Other Names:
  • Graft versus Host Disease prophylaxis regimen

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Donor engraftment
Time Frame: 100 days and 1 year post-transplant
as measured by chimerism
100 days and 1 year post-transplant

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to neutrophil engraftment
Time Frame: 100 days post-transplant
as measured by complete blood counts
100 days post-transplant
Time to platelet engraftment
Time Frame: 100 days post-transplant
as measured by complete blood counts
100 days post-transplant
Effect of BMT on pulmonary function
Time Frame: 90 days, 1 year, and 2 years post-transplant
as measured by pulmonary function tests
90 days, 1 year, and 2 years post-transplant
Effect of BMT on hepatic function
Time Frame: 90 days, 180 days, 1 year, and 2 years post-transplant
as measured by laboratory evaluations
90 days, 180 days, 1 year, and 2 years post-transplant
Effect of BMT on neurologic function
Time Frame: 90 days, 1 year, and 2 years post-transplant
as measured by cognitive testing and quality of life surveys
90 days, 1 year, and 2 years post-transplant
Effect of BMT on cardiac function
Time Frame: 90 days, 1 year, and 2 years post-transplant
as measured by echocardiograms
90 days, 1 year, and 2 years post-transplant
Effect of BMT on renal function
Time Frame: 90 days, 180 days, 1 year, and 2 years post-transplant
as measured by laboratory evaluations
90 days, 180 days, 1 year, and 2 years post-transplant
Pharmacokinetics of alemtuzumab
Time Frame: days -19, day 0, day +15, and day +30
as measured by maximum plasma concentration of alemtuzumab
days -19, day 0, day +15, and day +30
Pharmacokinetics of abatacept
Time Frame: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
as measured by maximum plasma concentration of abatacept
days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
Incidence of acute graft-versus-host disease (GVHD)
Time Frame: 1 year post-transplant
as measured by protocol grading scale
1 year post-transplant
Incidence of chronic graft-versus-host disease (GVHD)
Time Frame: 2 years post-transplant
as measured by protocol grading scale
2 years post-transplant
Immune reconstitution
Time Frame: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
as measured by research laboratory evaluations
days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Shalini Shenoy, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 20, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2033

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 3, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201611172

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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