PMT Therapy for Pulmonary Alveolar Proteinosis

Overseen By Brenna Carey

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Other PAP diseases, Pulmonary fibrosis, Chronic infections, Alcohol abuse, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 5 months

3 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

How is PMT Therapy different from other treatments for pulmonary alveolar proteinosis?

PMT Therapy is unique because it involves transplanting gene-corrected macrophages (a type of immune cell) to restore normal lung function, unlike traditional treatments like whole lung lavage, which physically removes surfactant buildup. This therapy directly addresses the genetic cause of the disease by correcting the defective GM-CSF signaling in the lungs. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment PMT Therapy for Pulmonary Alveolar Proteinosis?

Research shows that PMT Therapy, involving gene-corrected macrophages, was effective in mice with a similar genetic condition, leading to improved lung function and reduced disease symptoms. The therapy was safe, well-tolerated, and showed long-lasting benefits, suggesting potential effectiveness for humans with hereditary pulmonary alveolar proteinosis. ^{1 2 3 5 6}

Who Is on the Research Team?

Christopher Towe, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

Adults diagnosed with hereditary Pulmonary Alveolar Proteinosis (hPAP) who have either received Whole Lung Lavage therapy or have moderate disease severity needing treatment. Participants must be able to undergo bone marrow collection, use effective contraception if of childbearing potential, and provide written consent.

Inclusion Criteria

My CT scan shows widespread cloudy areas in my lungs.

I have been diagnosed with hPAP.

I am a woman who has been post-menopausal for more than 2 years or can use reliable birth control.

Exclusion Criteria

My lung condition is linked to an immune system problem.

History of medication or illicit drug abuse within 1 year prior to Study Visit 3

Any other medical, behavioral, or psychiatric condition that would interfere with the completion of Study Visits or assessments

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Participants undergo a 2-month observation period before treatment begins

8 weeks

Baseline

Baseline assessments are conducted to establish pre-treatment conditions

1 visit

Treatment

Participants receive three administrations of gene-corrected macrophages at 2-month intervals

5 months

3 visits (in-person)

Short-Term Follow-up

Participants are monitored for safety and effectiveness shortly after treatment

1 year

Medium-Term Follow-up

Participants continue to be monitored for safety and effectiveness

4 years

Long-Term Follow-up

Participants are monitored for long-term safety and effectiveness

10 years

What Are the Treatments Tested in This Trial?

Interventions

• PMT Therapy of hPAP

Trial Overview The trial is testing a new cell transplantation therapy where gene-corrected macrophages are delivered directly into the lungs via bronchoscopy. The aim is to assess safety and effectiveness for hPAP and understand lung macrophage functions.

How Is the Trial Designed?

Group I: Gene-Corrected Macrophages Experimental Treatment 1 Intervention

Autologous bone marrow CD34+ cell-derived, CSF2RA lentiviral vector-transduced macrophages (CSF2RA gene-corrected macrophages) by bronchoscopic instillation into individual lung segments.

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Gene-PMT therapy, which involves transplanting gene-corrected macrophages, was found to be highly effective in treating hereditary pulmonary alveolar proteinosis (hPAP) caused by Csf2ra mutations in a preclinical mouse model, leading to significant restoration of lung function and surfactant balance.

The therapy demonstrated long-term safety and tolerability, with no adverse effects observed in the treated mice, indicating its potential as a promising treatment for patients with hPAP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Gene-Pulmonary Macrophage Transplantation Therapy of PAP in Csf2ra-/- Mice. Arumugam, P., Suzuki, T., Shima, K., et al.[2020]

A new gene therapy approach using a self-inactivating lentiviral vector (Lv.EFS.CSF2RAcoop) has been developed to restore GM-CSF receptor function in macrophages of patients with hereditary pulmonary alveolar proteinosis (hPAP), showing promising results in preclinical studies.

The therapy demonstrated no adverse effects on healthy primary cells, indicating its safety for potential use in human patients with hPAP, paving the way for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Function and Safety of Lentivirus-Mediated Gene Transfer for CSF2RA-Deficiency. Hetzel, M., Suzuki, T., Hashtchin, AR., et al.[2018]

Pulmonary macrophage transplantation (PMT) was found to be a safe and effective treatment for a myeloid cell disorder in mice, correcting lung disease and preventing mortality without the need for myeloablation, which typically increases infection risk.

The therapeutic effects of PMT lasted for at least one year, demonstrating the potential for this approach as a specific therapy for children with hereditary pulmonary alveolar proteinosis (hPAP).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary macrophage transplantation therapy. Suzuki, T., Arumugam, P., Sakagami, T., et al.[2021]

Hereditary pulmonary alveolar proteinosis (hPAP) is caused by mutations in the CSF2RA/CSF2RB genes, leading to a buildup of surfactant in the lungs due to dysfunctional alveolar macrophages.

While whole lung lavage can relieve symptoms of hPAP, it carries risks of complications, making cell therapy a promising new treatment strategy for this rare lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Research progress of cell therapy in hereditary pulmonary alveolar proteinosis]. Zhang, MN., Jin, J., Song, XY., et al.[2023]

A young man with pulmonary alveolar proteinosis achieved complete remission after being treated with granulocyte-macrophage colony stimulating factor (GM-CSF), suggesting it as a promising new treatment option.

This case highlights the potential of GM-CSF as an alternative to the traditional whole lung lavage treatment for this rare condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy. Barraclough, RM., Gillies, AJ.[2019]

A new modified lavage technique (nMLT) for treating autoimmune pulmonary alveolar proteinosis, which includes controlled manual hyperinflation and chest percussion, significantly enhances the efficacy of whole lung lavage (WLL) by improving protein removal from the lungs.

In a study of 11 subjects, nMLT achieved a protein removal of approximately 9.80 grams per treatment, with a notable increase in protein yield after each cycle of washes, suggesting that this technique could optimize treatment while minimizing fluid volume used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Efficacy of Whole Lung Lavage Treatment in Alveolar Proteinosis Using a New Modified Lavage Technique. Grutters, LA., Smith, EC., Casteleijn, CW., et al.[2023]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Gene-Pulmonary Macrophage Transplantation Therapy of PAP in Csf2ra-/- Mice. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Function and Safety of Lentivirus-Mediated Gene Transfer for CSF2RA-Deficiency. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Pulmonary macrophage transplantation therapy. [2021]

4. China pubmed.ncbi.nlm.nih.gov

[Research progress of cell therapy in hereditary pulmonary alveolar proteinosis]. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Increased Efficacy of Whole Lung Lavage Treatment in Alveolar Proteinosis Using a New Modified Lavage Technique. [2023]