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Monoclonal Antibodies

Reduced Intensity BMT + Cyclophosphamide for Primary Immunodeficiency & Bone Marrow Failure

Phase 2
Recruiting
Led By Heather J Symons, MD, MHS
Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Available donor as follows: Cohort A - Fully HLA matched sibling or other first-degree family member, Cohort B - Fully HLA matched unrelated 10/10 donor using high-resolution DNA-based typing at the following genetic loci: HLA-A, -B, -C, DRB1, and DQB1, Cohort C - Mismatched unrelated donor at 8 or 9/10 alleles, using high-resolution typing as above, HLA-haploidentical family members of any degree who match at least one allele of each of the following genetic loci: HLA-A, -B, -C, DRB1, and DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype, The patient and/or legal guardian must sign informed consent for BMT, Patients with adequate organ function as measured by: Cardiac: Left ventricular ejection fraction (LVEF) at rest must be ≥ 35%. For patients aged <13 years, shortening fraction (SF) > 25% by echocardiogram or LVEF by multigated acquisition scan (MUGA) may be used, Hepatic: Bilirubin ≤ 3.0 mg/dL; and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Alkaline Phosphatase (ALP) < 5 x upper limit of normal (ULN), Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or glomerular filtration rate (GFR)) > 40 mL/min/1.73m2, Pulmonary: forced expiratory volume-one second (FEV1), forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide (DLCO) > 50% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92% on room air, Karnofsky or Lansky performance status ≥70%, Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time, or agree to abstinence
Confirmed diagnosis of Inherited Bone marrow failure disorders: Congenital amegakaryocytic thrombocytopenia (CAMT), Diamond Blackfan anemia (DBA), Shwachman Diamond Syndrome (SDS), Thrombocytopenia Absent Radii (TAR), Glanzmann's thrombasthenia (GT), Kostmann syndrome, Other PID, IDS, and IBMFS diagnoses as deemed appropriate by the PI
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 1 year
Awards & highlights

Study Summary

This trial will study how well a reduced intensity conditioning hematopoietic stem cell transplant (HSCT) and post-transplant cyclophosphamide (PTCy) work in patients with primary immune deficiencies (PID), immune dysregulatory syndromes (IDS), and inherited bone marrow failure syndromes (IBMFS).

Who is the study for?
This trial is for patients with primary immune deficiencies, immune dysregulatory syndromes, or inherited bone marrow failure. They must have a confirmed diagnosis and an available donor that matches their human leukocyte antigens (HLA) to varying degrees. Participants need proper organ function and agree to contraception if of childbearing potential.Check my eligibility
What is being tested?
The study tests reduced intensity conditioning hematopoietic stem cell transplant with post-transplant cyclophosphamide in patients with specific immune and bone marrow conditions. It aims to see how well donors' cells are accepted by the recipients' bodies using this method.See study design
What are the potential side effects?
Potential side effects include reactions from medications like Cyclophosphamide or Alemtuzumab such as nausea, hair loss, mouth sores; risks from low dose radiation; and complications related to the transplant like infections or graft-versus-host disease.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I have a diagnosed inherited bone marrow failure disorder.
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I have been diagnosed with a specific immune deficiency condition.
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I have been diagnosed with an immune dysregulation syndrome like IPEX or HLH.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~1 year
This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Donor Engraftment
Secondary outcome measures
Disease Free Survival at 1 year
Number of patients that have survived at 1 year

Trial Design

2Treatment groups
Experimental Treatment
Group I: PID/IDSExperimental Treatment7 Interventions
Alemtuzumab IV infusion over 2 hours on days -14, -13, and -12. Day -14 3 mg followed by 10 mg. Day -13 15 mg (or 10 mg if <10 kg). Day -12 20 mg (or 10 mg if <10 kg). Fludarabine 30 mg/m2/day IV infusion over 2 hours on days -6 to -2. Melphalan 70 mg/m2/day IV infusion over 30-60 minutes on days -3 and -2. (Or may be given as a single infusion of 140 mg/m2/day on day -2.) Total body irradiation: 200 cGy will be administered in a single fraction on day -1. Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Tacrolimus begins on day 5, at least 24 hours after completion of posttransplantation Cy at 0.015mg/kg IBW/dose IV over 4 hours every 12 hours. Mycophenolic acid mofetil (MMF) begins on day 5 at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).
Group II: IBMFSExperimental Treatment6 Interventions
Alemtuzumab IV infusion over 2 hours on days -14, -13, and -12. Day -14 3 mg followed by 10 mg. Day -13 15 mg (or 10 mg if <10 kg). Day -12 20 mg (or 10 mg if <10 kg). Fludarabine 30 mg/m2/day IV infusion over 2 hours on days -6 to -2. Melphalan 70 mg/m2/day IV infusion over 30-60 minutes on days -3 and -2. (Or may be given as a single infusion of 140 mg/m2/day on day -2.) Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Tacrolimus begins on day 5, at least 24 hours after completion of posttransplantation Cy at 0.015mg/kg IBW/dose IV over 4 hours every 12 hours. Mycophenolic acid mofetil (MMF) begins on day 5 at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Cyclophosphamide
FDA approved
Fludarabine
FDA approved
Alemtuzumab
FDA approved
Melphalan
FDA approved
Tacrolimus
FDA approved
Mycophenolate mofetil
FDA approved

Find a Location

Who is running the clinical trial?

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsLead Sponsor
556 Previous Clinical Trials
32,853 Total Patients Enrolled
Heather J Symons, MD, MHSPrincipal InvestigatorJohns Hopkins University

Media Library

Alemtuzumab (Monoclonal Antibodies) Clinical Trial Eligibility Overview. Trial Name: NCT04232085 — Phase 2
Primary Immunodeficiency Clinical Trial 2023: Alemtuzumab Highlights & Side Effects. Trial Name: NCT04232085 — Phase 2
Alemtuzumab (Monoclonal Antibodies) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04232085 — Phase 2
Primary Immunodeficiency Research Study Groups: PID/IDS, IBMFS

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

To what purpose is IBMFS most often put?

"The following conditions can all be treated by IBMFS: dermatitis, atopic, multiple sclerosis, and leukemia, myelocytic, acute."

Answered by AI

Are there similar treatments to IBMFS that have been explored in other research?

"At this moment, there are 1109 clinical trials studying IBMFS with 198 of them at Phase 3. Most of the research concerning IBMFS is happening in Philadelphia, but there are a total of 30680 locations running these trials."

Answered by AI

How does IBMFS impact human health?

"Even though there is some data supporting its safety, the lack of efficacy data knocks down IBMFS's score to a 2."

Answered by AI

How many people are sign ups for this research project?

"That is correct. The trial, which was originally posted on February 12th 2020 according to clinicaltrials.gov, is still looking for patients. Recently, on October 20th 2022, the study updated its information seeking 27 patients from 1 site."

Answered by AI

Who is the target demographic for this clinical trial?

"The eligibility criteria for this clinical study includes patients that have pancytopenia and are between the ages of 4 months to 40 years old. A total of 27 participants will be enrolled in the trial."

Answered by AI

Is this research being conducted with middle-aged adults?

"The required age range for prospective participants of this clinical trial is between 4 months to 40 years old."

Answered by AI

Are new patients able to join this clinical study?

"That is accurate. According to information found on clinicaltrials.gov, this particular trial began recruiting patients on February 12th 2020 and is still looking for 27 individuals from 1 centre."

Answered by AI
~4 spots leftby Dec 2024