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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

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

Confirmed diagnosis of Primary Immune Deficiencies: Chronic granulomatous disease (CGD), Wiskott-Aldrich syndrome (WAS), Hyper-Immunoglobulin M (IgM) syndrome, Common variable immunodeficiency (CVID), Leukocyte adhesion deficiency-1 (LAD-1), Severe Combined Immunodeficiency (SCID)

Must not have

Positive leukocytotoxic crossmatch, Prior allogeneic stem cell transplant, Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment, Diagnosis of idiopathic aplastic anemia, Fanconi Anemia, Dyskeratosis Congenita, or other short telomere syndrome, Seropositivity for the human immunodeficiency virus (HIV), Active Hepatitis B or C determined by serology and/or nucleic acid test (NAT), Female patients who are diagnosed as pregnant by beta human chorionic gonadotropin (bHCG) testing (per institutional practice) or who are breast-feeding, Active malignancy or within the timeframe for significant concern for relapse of prior malignancy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

All Individual Drugs Already Approved

Approved for 20 Other Conditions

No Placebo-Only Group

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.

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.

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.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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- Your blood test shows a bad reaction to other people's white blood cells. - You have had a transplant of someone else's stem cells. - You have an uncontrolled infection caused by bacteria, viruses, or fungi. - You have a specific type of anemia or genetic condition affecting your blood. - You have tested positive for HIV. - You have active Hepatitis B or C. - You are pregnant or breastfeeding. - You have an ongoing or recent history of cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Donor Engraftment

Secondary study objectives

Disease Free Survival at 1 year

Number of patients that have survived at 1 year

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

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