Health Trials

Base-Edited Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of CXCR4-WHIM

ConditionsWHIMWartsHypogammaglobulinemiaImmunodeficiencyMyelokathexis
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age3-75
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)

About this trial

Background:

Warts, hypogammaglobulinemia, infections and myelokathexis syndrome (WHIMs) is a rare disorder that affects the immune system. People with WHIMs can have severe infections all over their body. WHIMs is caused by a mutation in the CXCR4 gene. Treatment with drugs can help control the infections but does not cure the disorder. Researchers want to try a treatment where they collect stem cells from a person with WHIMS, use base-editing to replace the bad gene with a healthy version, and return the new cells to the person. This could cure WHIMs.

Objective:

To test a treatment using base-edited stem cells in people with WHIMs.

Eligibility:

People aged 3 years and older with WHIMs.

Design:

The study has 4 stages.

Stage 1: Screening. Participants will be screened at 1 or more visits. They will have a physical exam with blood tests. A sample of tissue and fluid (biopsy) will be taken from the bone marrow in the hip.

Stage 2: Apheresis. Blood will be taken from the body through a needle; the blood will pass through a machine that separates out the stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will undergo gene editing.

Stage 3: Treatment. Participants will stay in the hospital for about 4 weeks. They will receive 3 drugs to prepare their body for the procedure. Then the edited stem cells will be returned to their bloodstream. They will stay in the hospital until they recover.

Stage 4: Follow-up. Participants will have 8 follow-up visits over 5 years. Long-term visits will continue for 15 years.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged >= 3 years and weighing >=15 kg.

Confirmed CXCR c.1000C>T, pR334X mutation.

Ability to undergo apheresis for stem cell collection.

Medical lab data (historical) of neutropenia, or B cell dysfunction (low or absent IgG levels, or on IV gamma globulin.

Disqualifiers

Acute onset infection as indicated by symptoms such as persistent fevers, or imaging (new pneumonia on CT for example), isolated pathogen and requiring medical intervention.

Severe liver dysfunction with transaminases > 6 fold upper limit will be excluded until approval by hepatology consult who will provide mitigating plans for liver protection.

Renal dysfunction-serum creatinine >3.0 x ULN.

Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time >2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels).

Trial design

Design model

Single group

Treatments tested in this trial

  • Busulfan

    Drug

    Myeloid conditioning agent, administered once daily x 2 days, targeting a total AUC of 9000 micromol\*min/L.

  • Palifermin

    Drug

    Mucositis prophylaxis agent, will be administered at 60 mcg/kg/day for 3 days before initiation of busulfan (days -6 to -4), as well as for the 3 days following study agent administration (days 1 to 3).

  • Plerixafor

    Drug

    Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.

  • Filgrastim

    Drug

    Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.

  • Base-edited hematopoietic stem and progenitor cells

    Biological/Vaccine

    The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.

Treatment groups

10 Participants
are divided into 1 treatment group
Group A: Single arm studyExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

To evaluate the safety of base-edited autologous CD34+ cells

Safety of gene therapy using base-edited autologous hematopoietic stem and progenitor cells as measured by study agent-related adverse events and serious adverse events

Time frame
Initiated from the time of the infusion of base-edited cells through 2 years post-infusion

Secondary outcomes

1

Evaluate the efficacy of base-edited autologous CD34+ cells

Efficacy of gene therapy as determined by percentage of participants who have \>= 5 percent gene edited circulating myeloid cells

Time frame
Assessed 12 months post-infusion of base-edited cells
2

Evaluate genetic correction

Genetic correction as determined by the presence of \>200/uL edited neutrophils

Time frame
Assessed 12 months post-infusion of base edited cells
3

Evaluate immune reconstitution

Immune reconstitution as determined by: T, B, and NK cell number improvement from baseline; immunoglobulin production

Time frame
Assessed 12 months post-infusion of base edited cells
4

Evaluate clinical efficacy

Clinical efficacy as determined by: improvement from baseline problems (i.e., recurrent infections, wart burden)

Time frame
Assessed 12 months post-infusion of base edited cells

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Institute of Allergy and Infectious Diseases (NIAID)

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: