RECRUITING

Safety and Efficacy of PMT Therapy of hPAP

Conditions

Hereditary Pulmonary Alveolar Proteinosis Pulmonary Alveolar Proteinosis Pulmonary Macrophage Transplantation

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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

The major goal of this study is to evaluate a new type of cell transplantation therapy for individuals with hereditary PAP, study a new treatment that may be useful for treatment of other diseases, and research mechanisms that drive the development and function of lung macrophages.

Official Title

A First-In-Human Clinical Trial of Lentiviral-mediated CSF2RA Gene Transfer/Pulmonary Macrophage Transplantation Therapy of Hereditary Pulmonary Alveolar Proteinosis

Quick Facts

Study Start:2023-06-26

Study Completion:2038-10-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05761899

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:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Male or female with a confirmed diagnosis of hPAP defined as: * Homozygous or compound heterozygous CSF2RA mutations - AND - * A normal GM-CSF autoantibody test result - AND - * An abnormal STAT5-PI test result - OR - * An abnormal GM-CSF 50% effective concentration (EC50) test result 2. Diffuse ground glass opacification of the lungs visualized on a chest computed tomogram (CT) 3. History of prior receipt of WLL therapy or moderate hPAP lung disease severity requiring therapy in the opinion of the Clinical Site Investigator and/or Sponsor 4. Able to undergo bone marrow collection by routine clinical aspiration 5. 18 years of age or older on the date the Informed consent form (ICF) is signed 6. Females who have been post-menopausal for \>2 years or females of child-bearing potential after a confirmed menstrual period using a highly efficient method of contraception (as described in Section 11.4.2) for the period from 3 months prior to the first administration of gene-corrected macrophages until 12 months after the last administration of gene-corrected macrophages. Females of child-bearing potential must have a negative serum pregnancy test at Screening (Visit 1), at bone marrow collection (Visit 2), and immediately before each administration of gene-corrected macrophages (Visits 3, 5, 7), and must not be lactating. 7. Males of reproductive potential must agree to use condoms for the period from the 1st administration of gene-corrected macrophages until 12 months after the last dose of gene-corrected macrophages, have a partner who is not of child-bearing potential (i.e. men or females who have been post-menopausal for \>2 years), or have a female partner who is using adequate contraception as described in Section 11.4.2. 8. Signed written informed consent form (ICF)	1. History of a confirmed diagnosis of any other PAP-causing disease defined as: 1. PAP caused by function-altering mutations in CSF2RB, adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3), SFTPB, SFTPC, Thyroid Transcription Factor 1 (TTF-1), GATA-binding factor 2 (GATA2), SLC7A7, and methionyl-transfer RNA (tRNA) synthetase (MARS), or other genes demonstrated to cause PAP other than CSF2RA 2. PAP associated with an abnormal GM-CSF autoantibody test 3. PAP associated with hematologic disorders including but not limited to myelodysplasia, aplastic anemia, leukemia, multiple myeloma, lymphoma 4. PAP associated with non-hematologic malignancies 5. PAP associated with immune deficiency syndromes 6. PAP associated with chronic inflammatory syndromes 7. PAP associated with chronic infections including but not limited to human immunodeficiency virus, Mycobacteria tuberculosis or other Mycobacterial species, or other organisms 8. PAP associated with inhaled materials including but not limited to inorganic dusts (e.g., silica, titanium, indium, aluminum), organic dusts (e.g., sawdust, fertilizer); or gases/vapors (e.g., cleaning products, paints, and welding-related fumes) 2. Pulmonary fibrosis that is clinically significant in the opinion of Clinical Site Investigator and/or Sponsor 3. A confirmed (i.e., repeated) positive serum anti-GM-CSF receptor antibody test and/or a confirmed positive anti-lentiviral antibody test at the time of screening and prior to each administration of gene-corrected macrophages 4. History of receipt of any investigational agent within 3 months of Study Visit 3 5. History of active chronic infection (e.g., HIV, Hepatitis, others) at the time of Screening 6. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Study Visit 3, defined as more than 14 drinks/week for females or 21 drinks/week for males (1 drink - 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer, or 1.5 ounces (45 ml) of hard liquor) 7. History of medication or illicit drug abuse within 1 year prior to Study Visit 3, including but not limited to cocaine, heroin, or other opioids 8. Currently or planning to become pregnant between the Screening visit and Visit 14 and/or currently breast-feeding 9. Any other medical, behavioral, or psychiatric condition that would interfere with the completion of Study Visits or assessments in the opinion of the Clinical Site Investigator and/or Sponsor

Inclusion Criteria

Exclusion Criteria

1. Male or female with a confirmed diagnosis of hPAP defined as:
* Homozygous or compound heterozygous CSF2RA mutations - AND -
* A normal GM-CSF autoantibody test result - AND -
* An abnormal STAT5-PI test result - OR -
* An abnormal GM-CSF 50% effective concentration (EC50) test result
2. Diffuse ground glass opacification of the lungs visualized on a chest computed tomogram (CT)
3. History of prior receipt of WLL therapy or moderate hPAP lung disease severity requiring therapy in the opinion of the Clinical Site Investigator and/or Sponsor
4. Able to undergo bone marrow collection by routine clinical aspiration
5. 18 years of age or older on the date the Informed consent form (ICF) is signed
6. Females who have been post-menopausal for \>2 years or females of child-bearing potential after a confirmed menstrual period using a highly efficient method of contraception (as described in Section 11.4.2) for the period from 3 months prior to the first administration of gene-corrected macrophages until 12 months after the last administration of gene-corrected macrophages. Females of child-bearing potential must have a negative serum pregnancy test at Screening (Visit 1), at bone marrow collection (Visit 2), and immediately before each administration of gene-corrected macrophages (Visits 3, 5, 7), and must not be lactating.
7. Males of reproductive potential must agree to use condoms for the period from the 1st administration of gene-corrected macrophages until 12 months after the last dose of gene-corrected macrophages, have a partner who is not of child-bearing potential (i.e. men or females who have been post-menopausal for \>2 years), or have a female partner who is using adequate contraception as described in Section 11.4.2.
8. Signed written informed consent form (ICF)

1. History of a confirmed diagnosis of any other PAP-causing disease defined as:
1. PAP caused by function-altering mutations in CSF2RB, adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3), SFTPB, SFTPC, Thyroid Transcription Factor 1 (TTF-1), GATA-binding factor 2 (GATA2), SLC7A7, and methionyl-transfer RNA (tRNA) synthetase (MARS), or other genes demonstrated to cause PAP other than CSF2RA
2. PAP associated with an abnormal GM-CSF autoantibody test
3. PAP associated with hematologic disorders including but not limited to myelodysplasia, aplastic anemia, leukemia, multiple myeloma, lymphoma
4. PAP associated with non-hematologic malignancies
5. PAP associated with immune deficiency syndromes
6. PAP associated with chronic inflammatory syndromes
7. PAP associated with chronic infections including but not limited to human immunodeficiency virus, Mycobacteria tuberculosis or other Mycobacterial species, or other organisms
8. PAP associated with inhaled materials including but not limited to inorganic dusts (e.g., silica, titanium, indium, aluminum), organic dusts (e.g., sawdust, fertilizer); or gases/vapors (e.g., cleaning products, paints, and welding-related fumes)
2. Pulmonary fibrosis that is clinically significant in the opinion of Clinical Site Investigator and/or Sponsor
3. A confirmed (i.e., repeated) positive serum anti-GM-CSF receptor antibody test and/or a confirmed positive anti-lentiviral antibody test at the time of screening and prior to each administration of gene-corrected macrophages
4. History of receipt of any investigational agent within 3 months of Study Visit 3
5. History of active chronic infection (e.g., HIV, Hepatitis, others) at the time of Screening
6. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Study Visit 3, defined as more than 14 drinks/week for females or 21 drinks/week for males (1 drink - 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer, or 1.5 ounces (45 ml) of hard liquor)
7. History of medication or illicit drug abuse within 1 year prior to Study Visit 3, including but not limited to cocaine, heroin, or other opioids
8. Currently or planning to become pregnant between the Screening visit and Visit 14 and/or currently breast-feeding
9. Any other medical, behavioral, or psychiatric condition that would interfere with the completion of Study Visits or assessments in the opinion of the Clinical Site Investigator and/or Sponsor

Contacts and Locations

Study Contact

Bruce Trapnell

CONTACT

513-636-6361

Bruce.Trapnell@cchmc.org

Brenna Carey

CONTACT

513-636-8916

Brenna.Carey@cchmc.org

Principal Investigator

Christopher Towe, MD

PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Study Locations (Sites)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

United States

Collaborators and Investigators

Sponsor: Children's Hospital Medical Center, Cincinnati

Christopher Towe, MD, PRINCIPAL_INVESTIGATOR, Children's Hospital Medical Center, Cincinnati

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 Date2023-06-26

Study Completion Date2038-10-01

Study Record Updates

Study Start Date2023-06-26

Study Completion Date2038-10-01

Terms related to this study

Keywords Provided by Researchers

Pulmonary Alveolar Proteinosis
Pulmonary Macrophage Transplantation

Additional Relevant MeSH Terms

Hereditary Pulmonary Alveolar Proteinosis