RECRUITING

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

Conditions

Severe Sickle Cell Disease Bone Marrow Failure Syndromes Metabolic Disorders Immunologic Disorders Hemoglobinopathies Non-malignant Disorders Bone marrow transplant Transplant Transplantation Reduced Intensity Familial HLA mismatched

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2017-03-20

Study Completion:2031-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03128996

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.

Ages Eligible for Study:1 Day to 21 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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.	* 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)

Inclusion Criteria

Exclusion 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.

* 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)

Contacts and Locations

Study Contact

Shalini Shenoy, MD

CONTACT

314-454-6018

shalinishenoy@wustl.edu

Stephanie Hyde, CCRP

CONTACT

314-286-1180

stephanie.day@wustl.edu

Principal Investigator

Shalini Shenoy, MD

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Yale School of Medicine

New Haven, Connecticut, 06510

United States

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Shalini Shenoy, MD, PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

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 Registration Dates

Study Start Date2017-03-20

Study Completion Date2031-04

Study Record Updates

Study Start Date2017-03-20

Study Completion Date2031-04

Terms related to this study

Keywords Provided by Researchers

Bone marrow transplant
Transplant
Transplantation
Reduced Intensity
Familial HLA mismatched

Additional Relevant MeSH Terms

Severe Sickle Cell Disease
Bone Marrow Failure Syndromes
Metabolic Disorders
Immunologic Disorders
Hemoglobinopathies
Non-malignant Disorders