RecruitingPhase 1 / Phase 2

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
1 Day to 21 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests how well bone marrow transplants from a partly matched family member work and what harmful effects they cause. It uses a less intense treatment plan before transplant. It is for people younger than 21 who have a disease that is not cancer and need a bone marrow transplant.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be younger than 21 and need a transplant for a disease affecting bone marrow, metabolism (how the body uses food), the immune system, or hemoglobin (the protein that carries oxygen in blood).
  • For sickle cell disease, have at least one severe problem: stroke or ongoing high blood flow speeds in the brain despite transfusions; repeated serious chest problems; kidney damage; repeated hospital stays for pain needing long-term strong pain drugs and disrupting school and daily life; antibodies against donated red blood cells while needing ongoing transfusions; or repeated bone death or damage in several joints from poor blood supply.
  • For sickle cell disease, have hemoglobin S, the sickle cell form of hemoglobin, below 30% within 30 days before starting alemtuzumab.
  • Have a score of at least 50 on a test of ability to do daily activities. Meet the study’s heart and lung test limits.
  • Meet the study’s kidney and liver blood test limits.
  • If you have had many red blood cell transfusions, have a liver MRI to check iron levels. High iron levels require a liver tissue test showing no major scarring or active liver inflammation.
  • If able to become pregnant, agree to use two birth control methods together. Males must use effective barrier birth control or avoid sex. These rules last from signing consent through 12 months after transplant.
  • Provide written consent to join the study.

Who can't join

  • Have a fully tissue-matched brother or sister who can and will donate bone marrow.
  • Have cirrhosis or bridging fibrosis (serious liver scarring), or active hepatitis (liver inflammation).
  • Have an uncontrolled bacterial, viral, or fungal infection within 6 weeks before joining.
  • Have HIV infection or a known positive HIV test.
  • Have had a stem cell transplant before.
  • Have used an experimental drug or device, or a drug or device for an unapproved use, within 3 months before joining.
  • Be pregnant or breastfeeding.
  • Have an active autoimmune disease, where the immune system attacks the body, such as sarcoidosis, lupus, or scleroderma.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 sites (4)

CT

  • Yale School of Medicine · New Haven, CT 06510Lakshmanan Krishnamurti, MD · Study contactLakshmanan Krishnamurti, MD · Principal investigatorMore trials in New Haven

DE

MI

  • Helen DeVos Children's Hospital · Grand Rapids, MI 49503Troy Quigg, DO · Study contactTroy Quigg, DO · Principal investigatorMore trials in Grand Rapids

MO