Lung and Bone Marrow Transplant for Pulmonary Fibrosis

Recruiting at 1 trial location

Overseen By Paul Szabolcs, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Paul Szabolcs

Must not be taking: Live vaccines

Disqualifiers: Malignant conditions, HIV, Uncontrolled infections, others

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

Compensation: Varies

Number of Visits: Unknown

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a lung transplant before a bone marrow transplant can aid individuals with serious lung conditions like pulmonary fibrosis and resolve blood cell production issues. The aim is to first enhance lung function, allowing patients to safely undergo the bone marrow transplant to treat their blood condition. This trial suits those with severe lung disease and low blood counts impacting daily life, who can otherwise manage such major procedures. As a Phase 1, Phase 2 trial, the research seeks to understand the treatment's function in people and assess its effectiveness in an initial, smaller group, offering participants the opportunity to be among the first to benefit from this innovative approach.

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 to understand any specific requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lung transplants can be quite safe for people with lung diseases. Studies indicate that about 94% of patients survive the first year after a lung transplant, and even after five years, around 74% of patients continue to do well. This suggests that lung transplants are a dependable option for many.

For bone marrow transplants, safety can vary. Some patients, especially those with lung issues, may experience complications. These problems can affect up to 60% of patients, with serious risks if breathing support becomes necessary. However, with proper care, about 67% of patients survive for at least five years.

Both treatments have been used for a long time, and doctors have gained significant knowledge in managing the risks. It's important to discuss the potential benefits and risks with healthcare professionals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of lung and bone marrow transplants for pulmonary fibrosis because it offers a novel approach that could enhance long-term success rates. Unlike standard treatments that typically involve only lung transplantation, this method incorporates a bone marrow transplant from the same donor. The unique feature here is the use of CD3+/CD19+ depleted bone marrow, which helps reduce the risk of rejection and increases the compatibility of the transplanted lungs. Additionally, this approach uses a ≥1/6 HLA-matched T cell depleted bone marrow, aiming to improve immune tolerance and patient outcomes.

What evidence suggests that this trial's treatments could be effective for pulmonary fibrosis?

Research has shown that lung transplants can greatly improve breathing and quality of life for people with pulmonary fibrosis. Studies have found that recipients of a lung transplant live about six years longer, on average. In this trial, participants will undergo both lung and bone marrow transplants (BMT). BMT helps restore the blood and immune system. Although BMT can cause complications, early treatment often leads to good results. Combining these two transplants in this study might improve both lung and blood functions, offering hope for those with serious lung and blood issues. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with severe lung diseases like Pulmonary Fibrosis or COPD and bone marrow failure, who are eligible for a lung transplant. They must understand the study, not be pregnant, agree to birth control post-transplant, and have no allergies to stem cell product ingredients or recent live vaccines.

Inclusion Criteria

I have advanced lung disease like Pulmonary Fibrosis or COPD.

Patients must have low blood cell counts or abnormal blood tests that make them unsuitable for long-term treatment with immunosuppressive therapy. They must also meet at least one of the following criteria: low white blood cell counts, low platelet counts, or low red blood cell counts confirmed by repeat testing; normal kidney function and liver function; normal heart function; negative pregnancy test for females. If sexually active, patients must agree to use birth control. They will also be counseled about potential infertility risks and advised to consider sperm or egg freezing.

I am eligible for a lung transplant according to UNOS standards.

Exclusion Criteria

Inability or unwillingness of a participant to give written informed consent or comply with study protocol

I have a cancer diagnosis.

I am currently pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lung Transplantation

Participants undergo cadaveric, partially HLA-matched lung transplantation to restore pulmonary function

8 weeks

Multiple visits for pre-transplant evaluation and post-transplant monitoring

Bone Marrow Transplantation

Participants receive CD3+/CD19+ depleted bone marrow transplantation from the same donor to restore hematologic function

6 months

Regular visits for transplantation and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and long-term complications after transplantation

Up to 2 years

Regular visits for monitoring immune tolerance and complications

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab
• Bone Marrow Transplantation
• Fludarabine
• G-CSF
• Hydroxyurea
• Lung Transplantation
• Rituximab
• Thiotepa

Trial Overview The study tests if performing a lung transplant before a bone marrow transplant can restore lung function enough to proceed with bone marrow transplantation using various drugs (Rituximab, Alemtuzumab) and stem cells to improve blood cell counts.

How Is the Trial Designed?

Group I: Lung and Bone Marrow Transplantation Experimental Treatment 7 Interventions

All patients will undergo a cadaveric, partially HLA-matched lung transplantation followed by a CD3+/CD19+ depleted BMT from the same donor. In this study, the investigators will use a ≥1/6 HLA-matched T cell depleted bone marrow transplantation from a cadaveric organ donor with an identical ABO blood type as the recipient. Prior to transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device. Subjects will undergo lung transplantation utilizing standard induction regimens selected by the CO-PIs based on the subject's underlying comorbidities and allosensitization. Rituximab may be initiated prior to the lung transplantation with tacrolimus as the ongoing maintenance immunosuppression. Subjects will undergo BMT utilizing CD3+/CD19+-depleted bone marrow with bone marrow conditioning beginning no less than 8 weeks after lung transplantation. Bone marrow will be recovered alongside solid organs and will be processed and cryopreserved.

Bone Marrow Transplantation is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Bone Marrow Transplant for:

• Leukemia
• Lymphoma
• Multiple Myeloma
• Aplastic Anemia
• Sickle Cell Disease
• Thalassemia
• Immune Deficiency Disorders

Approved in United States as Bone Marrow Transplant for:

• Acute Leukemia
• Chronic Leukemia
• Hodgkin's Lymphoma
• Non-Hodgkin's Lymphoma
• Multiple Myeloma
• Aplastic Anemia
• Sickle Cell Disease
• Thalassemia
• Immune Deficiency Disorders

Approved in Canada as Bone Marrow Transplant for:

• Leukemia
• Lymphoma
• Multiple Myeloma
• Aplastic Anemia
• Sickle Cell Disease
• Thalassemia
• Immune Deficiency Disorders

Approved in Japan as Bone Marrow Transplant for:

• Leukemia
• Lymphoma
• Multiple Myeloma
• Aplastic Anemia
• Sickle Cell Disease
• Thalassemia
• Immune Deficiency Disorders

Approved in China as Bone Marrow Transplant for:

• Leukemia
• Lymphoma
• Multiple Myeloma
• Aplastic Anemia
• Sickle Cell Disease
• Thalassemia
• Immune Deficiency Disorders

Approved in Switzerland as Bone Marrow Transplant for:

• Leukemia
• Lymphoma
• Multiple Myeloma
• Aplastic Anemia
• Sickle Cell Disease
• Thalassemia
• Immune Deficiency Disorders

Who Is Running the Clinical Trial?

Paul Szabolcs

Lead Sponsor

Trials

8

Recruited

230+

Published Research Related to This Trial

Bone marrow transplant (BMT) is a preferred treatment for certain blood diseases, but it carries significant risks, including complications from the conditioning regimen like neutropenia and thrombocytopenia, which can lead to infections and bleeding.

Graft-versus-host disease (GVHD) is a common complication after allogeneic BMT, occurring when donor T cells attack the recipient's tissues, and patients require ongoing medical care for about a year post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-bone marrow transplant patient management. Poliquin, CM.[2018]

Lung transplantation (LTx) is now the preferred treatment for many patients with end-stage lung diseases, with improved post-transplant survival rates, although the median survival remains at 5.8 years.

LTx can also be successfully performed in patients with complex conditions, such as those needing combined heart-lung or liver-lung transplants, and in patients with severe lung issues following hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Lung Transplantation, Heart-Lung Transplantation, Liver-Lung Transplantation, and Combined Hematopoietic Stem Cell Transplantation and Lung Transplantation. Gadre, S., Turowski, J., Budev, M.[2018]

A successful left lower lobe lung transplant was performed from a mother to her child, who had previously undergone a bone marrow transplant and developed severe pulmonary fibrosis, indicating the potential for organ donation in complex medical histories.

The child experienced an uncomplicated surgery and postoperative course, with a gradual recovery, and one year later, the patient is doing well, suggesting that careful management and short-term immunosuppression can lead to positive outcomes in lung transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of a lobe of lung from mother to child following previous transplantation with maternal bone marrow. Svendsen, UG., Aggestrup, S., Heilmann, C., et al.[2021]

Lung transplantation has emerged as a viable treatment option for various pulmonary diseases, with three main types: single lung, double lung, and heart-lung transplants, each indicated for specific conditions.

Post-surgery management is crucial, focusing on immunosuppression therapy and monitoring for complications like graft rejection and obliterans bronchiolitis, which is a significant long-term concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current status of lung transplantation]. García Río, FJ., García Talavera, I., Vázquez, M., et al.[2006]

Bone marrow transplantation is a key treatment for conditions like aplastic anemia and severe combined immunodeficiency, but many patients lack compatible donors, highlighting the need for improved techniques.

Recent advances have reduced complications such as graft rejection and graft-versus-host disease, and using autologous stem cells may eliminate many issues associated with allogeneic transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation in Canada. Buskard, NA.[2018]

Lung transplantation is an effective treatment for patients with end-stage pulmonary diseases, with specific indications for chronic obstructive or infective lung diseases and conditions with high pulmonary resistance.

From 1983 to April 1989, the survival rates for lung transplants were 60% for single lung transplants and 57% for double lung transplants, indicating a significant success in these procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Status of lung transplantation: developments, indications and results]. Weder, W., Largiadèr, F.[2006]

Single-lung transplantation (SLT) significantly reduces pulmonary artery pressure and improves oxygenation in patients with end-stage lung diseases and pulmonary hypertension, as shown by a study of 22 recipients over a period from 2002 to 2005.

Post-transplantation, systolic pulmonary artery pressure decreased from 50.00 mm Hg to 39.5 mm Hg, and the oxygenation index (PaO2/FiO2) improved from 241.26 mm Hg to 348.23 mm Hg, indicating the efficacy of SLT in enhancing respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Single-lung transplantation for end-stage pulmonary parenchymal diseases with pulmonary hypertension]. Zhu, YH., Chen, JY., Zheng, MF., et al.[2007]

The paper outlines the indications for various transplant procedures, including unilateral, bilateral, heart-lung, and lobar transplants, specifically for conditions like emphysema, cystic fibrosis, primary pulmonary hypertension, and pulmonary fibrosis.

It also provides a historical overview of these transplant procedures, highlighting their evolution and significance in treating severe lung diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indications. Unilateral, bilateral, heart-lung, and lobar transplant procedures. Patterson, GA.[2019]

Bone marrow transplantation (BMT) is a life-saving treatment for blood cancers, but it can lead to serious pulmonary complications, particularly chronic graft-versus-host disease (GVHD), which negatively impacts survival rates.

This case report highlights a successful lung transplantation for a patient with severe lung GVHD following BMT for acute lymphoblastic leukemia, suggesting that lung transplantation may be a viable treatment option for respiratory failure in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Single-Lung Transplant for Severe Lung Graft-Versus-Host Disease Two Years After Sibling Allograft for Acute Lymphoblastic Leukemia: A Case Report. Irhimeh, MR., Musk, M., Cooney, JP.[2018]

Lung transplant is a critical procedure for patients with terminal and irreversible pulmonary diseases, with over 3,500 transplants performed in Spain, indicating its growing acceptance and application.

The review covers essential aspects of lung transplants, including types, indications, contraindications, procedures, and immunosuppressive treatments, highlighting the importance of understanding both the benefits and potential side effects of the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What the family doctor must know about lung transplant (Part 1)]. Zurbano, L., Zurbano, F.[2018]

In a study of 128 lung transplant recipients, double lung transplants (DLT) showed significantly better 5-year survival rates (75%) compared to single lung transplants (SLT) (51%), highlighting the advantages of DLT for patients with end-stage lung diseases.

Patients with cystic fibrosis had the highest overall survival rates, with 87% reaching 1-year survival, while those with primary pulmonary hypertension had the lowest short-term survival, particularly after SLT, indicating that DLT is preferable for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Lung Transplant vs Double Lung Transplant: A Single-Center Experience With Particular Consideration for Idiopathic Pulmonary Arterial Hypertension. Antończyk, R., Stącel, T., Urlik, M., et al.[2020]

Lung transplants can be categorized into single lung, double lung en bloc, and bilateral-sequential procedures, each tailored to specific lung diseases like pulmonary fibrosis and emphysema, highlighting the importance of matching the transplant type to the patient's condition.

The future of lung transplantation relies on ongoing research, better preservation techniques, enhanced donor care, and increasing the number of available donors to improve outcomes and expand treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary transplant. Transplantation for end-stage lung disease: a nurse's perspective. Dickey, D.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8348211/

Pulmonary Complications in Hematopoietic Stem Cell ... Up to 85% of IPS cases are non-responsive to corticosteroids and progress to respiratory failure with up to 90% requiring mechanical ventilation [22,28].

2. astctjournal.org astctjournal.org/article/S1083-8791(14)00225-0/fulltext

Outcomes of Lung Transplantation after Allogeneic ... Survival at 1 year and 5 years after LT was 89% and 37%, respectively. In the medical literature between 1992 and July 2013, we identified 20 articles ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03500731

NCT03500731 | Lung and Bone Marrow Transplantation ... The primary purpose of the study is to evaluate the safety and efficacy of performing lung transplantation followed by cadaveric, partially HLA-matched ...

4. nature.com nature.com/articles/s41409-020-01137-1

Transplant characteristics and self-reported pulmonary ... We found that pulmonary outcomes were frequently reported in transplanted and non-transplanted childhood cancer survivors, indicating a strong need for long- ...

5. publications.ersnet.org publications.ersnet.org/content/breathe/20/3/240043

Pulmonary complications of bone marrow transplantation Outcomes are usually good with prompt recognition and treatment, with mortality of about 5% after 100 days post-HSCT versus 1.8% in patients with no PERDS [17].

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724004299

Late-Onset Noninfectious Pulmonary Complications after ... Five-year allo-HSCT survival as high as 67% has been reported, comparable to the outcomes of other end-stage pulmonary disorders [35]. Appropriate patient ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12301330/

Safety and long-term efficacy of autologous hematopoietic cell ... Overall survival was 16/17 (94.2%). Concerning TRM, there was one (1/17, 5.8%) death early post-transplant. In this specific cohort of selected ...