Venetoclax for Idiopathic Pulmonary Fibrosis

Recruiting at 2 trial locations

Overseen By Steven R Duncan, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Malignancy, Acute infection, Severe cardiovascular, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

3 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing ABT-199, a drug that helps certain immune cells die, in patients with idiopathic pulmonary fibrosis (IPF). IPF is a serious lung disease with no cure. The drug works by blocking a protein that prevents cell death, potentially reducing lung damage. This could offer significant benefits for IPF patients. ABT-199 has shown promise in reducing lung inflammation and fibrosis in animal models of pulmonary fibrosis.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that are potent CYP3A4 inhibitors or inducers during the 24-week treatment period. This includes drugs like ritonavir, ketoconazole, and rifampin, among others.

How does the drug Venetoclax differ from other treatments for idiopathic pulmonary fibrosis?

Venetoclax is unique because it is an oral drug that targets a specific protein called BCL-2, which helps cancer cells survive. While it is primarily used for blood cancers like chronic lymphocytic leukemia, its novel mechanism of action as a BCL-2 inhibitor is being explored for other conditions, such as idiopathic pulmonary fibrosis, where standard treatments may not be well-established. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 40-85 with a confirmed diagnosis of idiopathic pulmonary fibrosis (IPF) that's been known for less than 5 years and have at least moderate lung function. Participants must be able to consent, follow the study plan, and not be on certain other drugs or have major health issues like severe liver problems, heart conditions, recent infections, kidney disease requiring dialysis, or a history of cancer in the last 5 years.

Inclusion Criteria

You can breathe out a lot of air compared to what is expected for someone your size.

I have been diagnosed with idiopathic pulmonary fibrosis.

Ability and willingness to give informed consent and adhere to study requirements

Exclusion Criteria

I am a man who agrees to use contraception or remain abstinent and not donate sperm during and 90 days after the study.

I have not had a severe heart issue or stroke in the last 3 months.

I do not have untreated heart rhythm problems or a family history of long QT syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Venetoclax 100 mg daily for 3 weeks

3 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Venetoclax

Trial Overview The trial tests Venetoclax's safety and effectiveness in treating IPF. Researchers believe it may help by causing problematic cells in the lungs to self-destruct. The drug has worked well before in leukemia patients without serious side effects.

Participant Groups

Group I: treatment Experimental Treatment 1 Intervention

Venetoclax 100 mg daily for 3 weeks

Venetoclax is already approved in United States, European Union for the following indications:

Approved in United States as Venclexta for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Approved in European Union as Venclyxto for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

The combination of venetoclax with bendamustine-rituximab (BR) was found to be safe and tolerable in a study of 60 patients with relapsed/refractory non-Hodgkin's lymphoma, with the recommended phase II dose established at 800 mg daily.

The overall response rate to the treatment was 65%, with a median duration of response of 38.3 months, indicating preliminary efficacy for this combination therapy in managing B-cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. de Vos, S., Swinnen, LJ., Wang, D., et al.[2021]

References

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

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

2. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]

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

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. [2021]