RECRUITING

Leniolisib for Immune Dysregulation in PIDs

Conditions

Primary Immunodeficiency Disorders (PIDs)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is an exploratory, non-randomized, open-label, within-patient dose escalation study. The primary objective is to assess safety and tolerability of leniolisib. Secondary objectives include assessments of PK/PD, and to explore clinical efficacy measures with administration of three different dose levels of leniolisib.

Official Title

A Study to Assess Safety and Tolerability, and Explore Efficacy of Leniolisib for Immune Dysregulation in Primary Immunodeficiency Disorders

Quick Facts

Study Start:2024-10-21

Study Completion:2025-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06549114

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subjects 12 to 75 years of age. 2. Diagnosed with a PID due to disease-causing pathogenic or likely pathogenic variant(s) in the following genes: SOCS1, PTEN, CTLA4, NFKB1 (only those variants leading to NFKB pathway activation), or FAS (germline or somatic), or diagnosed with RAS associated leukoproliferative disorder (and not juvenile myelomonocytic leukemia \[JMML\]) due to somatic variants in NRAS or KRAS. 3. Subjects must have 1 or more of the following: * One or more blood cytopenias related to the underlying PID defined as hemoglobin \<10 g/dL, platelet count \<100,000/µL, or neutrophil count \<1000/µL * Splenomegaly evident by CT imaging with craniocaudal spleen measurement \>10 cm * Lymphadenopathy evident by CT imaging with at least 1 measurable index lymph node (long axis \>1.5 cm) as per Cheson methodology * GLILD or other PID-related ILD with quantifiable CT chest imaging findings evident on baseline CT scan 4. At screening, vital signs. * Systolic blood pressure 80-139 mm Hg * Diastolic blood pressure 50-89 mm Hg * Pulse rate 50-110 bpm * Oxygen saturation 93-100% 5. Subjects or their legal representatives (for subjects under the age of 18 years) must be able to provide written informed consent.	1. Subject has had a successful hematopoietic stem-cell transplant (HSCT). 2. Previous or concurrent use of immunosuppressive medication, such as: * Use of an mTOR inhibitor or a PI3Kδ inhibitor within 3 weeks prior to first dosing . * Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing. * Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib, or other JAK inhibitors within 3 weeks prior to first dosing. * Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing. * Other immunosuppressive agents expected to have a significant impact on immune cell number or function. * Abatacept is allowed during study if the subject has been receiving a stable dosing regimen for more than 3 months prior to first dosing. 3. Subject is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks or 5 half-lives (whichever is longer) prior to first dosing. 4. History of hypersensitivity to the study drug or to drugs of similar chemical classes. 5. Current use of medication known to be a strong inhibitor, or moderate or strong inducer, of isoenzyme P450 CYP3A. 6. Current use of medications that act as BCRP, OATP1B1, and OATP1B3 substrates. 7. Subject has a history or current electrocardiogram (ECG) abnormalities indicating a significant risk of safety for subjects participating in the study 8. History of acquired immunodeficiency diseases, including a positive HIV test result at screening. 9. Uncontrolled chronic or recurrent infectious disease (except those considered to be characteristic of a PID) or evidence of tuberculosis infection 10. Any surgical or medical condition which may jeopardize the subject in case of participation in the study, or might significantly alter the absorption, distribution, metabolism, or excretion of drugs. 11. A positive hepatitis B surface antigen, positive hepatitis B PCR, positive hepatitis C PCR, or positive hepatitis C antibody result at screening. 12. Administration of live vaccines starting from 6 weeks before first dose of study medication. 13. Subject has a previous diagnosis of lymphoma within 1 year of the first dose of study medication. 14. Subject has a history of malignancy (except lymphoma) within 3 years before the first dose of study medication, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix. 15. Subject has uncontrolled post-transplant lymphoproliferative disease (PTLD)-like EBV related lymphoproliferative disease. 16. Donation or loss of 400 mL or more of blood within 8 weeks before the first dose. 17. Subject has had major surgery requiring hospitalization or radiotherapy within 4 weeks prior to the first dose or has a planned or expected major surgical procedure during the study period. 18. Pregnant or nursing (lactating) individuals,. 19. Individuals of child-bearing potential, unless they are using highly effective methods of contraception.

Inclusion Criteria

Exclusion Criteria

1. Subjects 12 to 75 years of age.
2. Diagnosed with a PID due to disease-causing pathogenic or likely pathogenic variant(s) in the following genes: SOCS1, PTEN, CTLA4, NFKB1 (only those variants leading to NFKB pathway activation), or FAS (germline or somatic), or diagnosed with RAS associated leukoproliferative disorder (and not juvenile myelomonocytic leukemia \[JMML\]) due to somatic variants in NRAS or KRAS.
3. Subjects must have 1 or more of the following:
* One or more blood cytopenias related to the underlying PID defined as hemoglobin \<10 g/dL, platelet count \<100,000/µL, or neutrophil count \<1000/µL
* Splenomegaly evident by CT imaging with craniocaudal spleen measurement \>10 cm
* Lymphadenopathy evident by CT imaging with at least 1 measurable index lymph node (long axis \>1.5 cm) as per Cheson methodology
* GLILD or other PID-related ILD with quantifiable CT chest imaging findings evident on baseline CT scan
4. At screening, vital signs.
* Systolic blood pressure 80-139 mm Hg
* Diastolic blood pressure 50-89 mm Hg
* Pulse rate 50-110 bpm
* Oxygen saturation 93-100%
5. Subjects or their legal representatives (for subjects under the age of 18 years) must be able to provide written informed consent.

1. Subject has had a successful hematopoietic stem-cell transplant (HSCT).
2. Previous or concurrent use of immunosuppressive medication, such as:
* Use of an mTOR inhibitor or a PI3Kδ inhibitor within 3 weeks prior to first dosing .
* Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, or alemtuzumab within 6 months prior to first dosing.
* Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine, methotrexate, tacrolimus, ruxolitinib, or other JAK inhibitors within 3 weeks prior to first dosing.
* Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing.
* Other immunosuppressive agents expected to have a significant impact on immune cell number or function.
* Abatacept is allowed during study if the subject has been receiving a stable dosing regimen for more than 3 months prior to first dosing.
3. Subject is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks or 5 half-lives (whichever is longer) prior to first dosing.
4. History of hypersensitivity to the study drug or to drugs of similar chemical classes.
5. Current use of medication known to be a strong inhibitor, or moderate or strong inducer, of isoenzyme P450 CYP3A.
6. Current use of medications that act as BCRP, OATP1B1, and OATP1B3 substrates.
7. Subject has a history or current electrocardiogram (ECG) abnormalities indicating a significant risk of safety for subjects participating in the study
8. History of acquired immunodeficiency diseases, including a positive HIV test result at screening.
9. Uncontrolled chronic or recurrent infectious disease (except those considered to be characteristic of a PID) or evidence of tuberculosis infection
10. Any surgical or medical condition which may jeopardize the subject in case of participation in the study, or might significantly alter the absorption, distribution, metabolism, or excretion of drugs.
11. A positive hepatitis B surface antigen, positive hepatitis B PCR, positive hepatitis C PCR, or positive hepatitis C antibody result at screening.
12. Administration of live vaccines starting from 6 weeks before first dose of study medication.
13. Subject has a previous diagnosis of lymphoma within 1 year of the first dose of study medication.
14. Subject has a history of malignancy (except lymphoma) within 3 years before the first dose of study medication, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
15. Subject has uncontrolled post-transplant lymphoproliferative disease (PTLD)-like EBV related lymphoproliferative disease.
16. Donation or loss of 400 mL or more of blood within 8 weeks before the first dose.
17. Subject has had major surgery requiring hospitalization or radiotherapy within 4 weeks prior to the first dose or has a planned or expected major surgical procedure during the study period.
18. Pregnant or nursing (lactating) individuals,.
19. Individuals of child-bearing potential, unless they are using highly effective methods of contraception.

Contacts and Locations

Study Contact

Gulbu Uzel, MD

CONTACT

240-678-2572

guzel@mail.nih.gov

Principal Investigator

Gulbu Uzel, M.D.

PRINCIPAL_INVESTIGATOR

National Institutes of Health (NIH)

Study Locations (Sites)

National Institute of Health

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: Pharming Technologies B.V.

Gulbu Uzel, M.D., PRINCIPAL_INVESTIGATOR, National Institutes of Health (NIH)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-21

Study Completion Date2025-10

Study Record Updates

Study Start Date2024-10-21

Study Completion Date2025-10

Terms related to this study

Additional Relevant MeSH Terms

Primary Immunodeficiency Disorders (PIDs)