Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

NCT06730126 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001824001824-I
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system caused by a mutation in the FAS gene. In ALPS, the body stores too many germ-fighting cells called lymphocytes. This can lead to an enlarged spleen and lymph nodes. Current treatments for ALPS can have many adverse effects. Better treatments for ALPS are needed. Objective: To test a study drug (soquelitinib) in people with ALPS. Eligibility: People aged 16 years and older with ALPS. Design: Participants will have 8 clinic visits and 6 remote visits within 1 year. Participants will be screened. They will have a physical exam with blood and urine tests. Some may have tests of their lung function. Soquelitinib is a tablet taken by mouth twice a day. Participants will record their doses and any symptoms on a paper or online form. Blood tests and other procedures will be repeated during study visits. Three visits will include imaging scans. Participants will lie on a table that slides through a doughnut-shaped machine while X-rays capture pictures of the inside of their body. Some participants may be able to remain in the study for a second year.

Conditions

Autoimmune Lymphoproliferative Syndrome

Keywords

Autoimmune Lymphoproliferative Syndrome; Fas; Hypersplenism; Lymphoproliferation; Interleukin-2 Inducible T-cell Kinase; Soquelitinib; Targeted Treatment

Outcome Measures

Primary Outcomes (1)

• Reduction of spleen volume or target lymph node volume by 25% from baseline to day 90, assessed by CT or PET/CT scan.

  To determine the efficacy of soquelitinib in reducing spleen volume or target lymph node volume in people with ALPS-FAS.

  Day 90

Secondary Outcomes (7)

• Shrinkage in spleen volume from baseline to day 90.

  Day 90

• Shrinkage in target lymph node volume from baseline to day 90.

  Day 90

• Reduction of cytopenias by one severity level from baseline to day 90

  Day 90

• Reduction in prednisone dosage.

  End of Study

• Grade 3 or 4 systemic infections within 360 days.

  Day 360

Study Arms (1)

Interventional

EXPERIMENTAL

The initial dosage for stage 1 of this study is 200 mg twice daily for up to 360 days. If stage 1 is repeated because there are no successes at this dosage, then it will be increased to 400 mg twice daily for up to 360 days. Alternatively, if there are safety concerns at either dosage, then it will be decreased to 100 mg twice daily for up to 360 days.

Drug: Soquelitinib

Interventions

Soquelitinib DRUG

Soquelitinib is an ITK inhibitor in clinical development for treating relapsed/refractory T-cell lymphoma.

Interventional

Eligibility Criteria

• Age: 16 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Aged \>= 16 years.
• Able to provide informed consent (for ages \>= 18 years) or has a parent(s) or guardian(s) who can provide permission to participate on their behalf (for ages \<18 years).
• Has a documented diagnosis of ALPS-FAS.
• Has clinical evidence of active disease, defined as at least one enlarged lymph node and/or enlarged spleen.
• If currently on corticosteroid therapy, then dose is less than 20 mg/day (prednisone equivalent) and has been stable for at least 4 weeks.
• For participants to be seen at the NIH CC, co-enrolled on NIH protocol 93-I-0063.
• Participants who can become pregnant or who can impregnate their partner must agree to either remain sexually abstinent or use two highly effective methods of contraception when engaging in sexual activities that can result in pregnancy, beginning 28 days before baseline until 3 months after the last dose. One method must be a barrier (eg, internal or external condom, cervical cap, or diaphragm). The second method may be any of the following:
• a. Oral contraceptive pill or hormonal patch or ring.
• b. Parenteral hormonal contraceptive implant.
• c. Intrauterine device.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Profound grade 3 or 4 cytopenias that cannot be improved with immunomodulatory treatments prior to enrolling in the clinical trial and starting the study drug. Per investigator discretion, individuals on a single agent may be included if the dose is stable for 12 weeks at screening and is not expected to confer additive toxicity.
• Renal impairment, defined as serum creatinine \>1.5 mg/dL (or 133 micromol/L) or estimated glomerular filtration rate \<60 mL/min/1.73 m\^2.
• Liver impairment, defined as bilirubin, alanine aminotransferase, or aspartate aminotransferase greater than 2.5 times the upper limit of normal.
• History of EBV-associated lymphoma.
• Active EBV infection with EBV load \>300 copies/mL.
• Tuberculosis infection (active or latent) or undergoing tuberculosis treatment.
• Infection with HIV or hepatitis B or C.
• Current other invasive or systemic fungal, bacterial, or viral infection requiring therapy.
• History of opportunistic infection within the previous 180 days.
• History of invasive malignancy that required systemic therapy within the last 3 years.
• Current use of moderate or strong cytochrome P450 isozyme (CYP)3A inhibitors or inducers that cannot be stopped before day 0.
• Current use of P-glycoprotein (P-gp) inhibitors that cannot be stopped before day 0.
• Known hypersensitivity or contraindication to CT contrast agent.
• Pregnant or breastfeeding.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Price S, Shaw PA, Seitz A, Joshi G, Davis J, Niemela JE, Perkins K, Hornung RL, Folio L, Rosenberg PS, Puck JM, Hsu AP, Lo B, Pittaluga S, Jaffe ES, Fleisher TA, Rao VK, Lenardo MJ. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014 Mar 27;123(13):1989-99. doi: 10.1182/blood-2013-10-535393. Epub 2014 Jan 7.

  PMID: 24398331 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Autoimmune Lymphoproliferative Syndrome; Autoimmune Lymphoproliferative Syndrome, Type IA; Hypersplenism

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Autoimmune Diseases; Immune System Diseases; Immunoproliferative Disorders; Splenic Diseases

Study Officials

• V. Koneti Rao, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alanvin D Orpia, R.N.

CONTACT

(240) 550-3663; alanvin.orpia@nih.gov

V. Koneti Rao, M.D.

CONTACT

(301) 496-6502; kr191c@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 12, 2024
• Study Start: March 10, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2025-11-28

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Following interim review and/or completion of study.
• Access Criteria: Requests are reviewed by PI.

Locations

US (3)