Voruciclib + Venetoclax for Leukemia and Lymphoma

Not currently recruiting at 11 trial locations

Overseen By MEI Pharma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MEI Pharma, Inc.

Must not be taking: Warfarin, Anticancer, Investigational, others

Disqualifiers: Pneumonitis, CNS involvement, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable, up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with certain types of blood cancer, including leukemia and lymphoma, that have returned or stopped responding to standard treatments. Researchers are testing the safety and effects of two drugs, voruciclib and venetoclax (also known as Venclexta), either individually or in combination. Suitable candidates for this trial have experienced worsening blood cancer after trying at least two treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, like warfarin, anti-cancer drugs, or investigational agents. If you're on immunosuppressive treatments or certain medications for HIV, you may also need to stop those before starting the trial.

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

Research has shown that voruciclib, when used alone, is generally safe and well-tolerated. In previous studies, patients taking voruciclib did not experience serious side effects that would prevent increasing the dose up to 200 mg. This suggests that most people can handle the drug at these levels.

When combined with venetoclax, voruciclib remains safe. Studies have shown that this combination does not cause more side effects than taking voruciclib alone.

Overall, both voruciclib alone and with venetoclax have been well-tolerated, with no significant reports of reduced blood cell production or other severe side effects in the research conducted so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Voruciclib and Venetoclax for leukemia and lymphoma because they offer a novel approach compared to standard treatments like chemotherapy and targeted therapies. Voruciclib is unique because it inhibits CDK9, a protein involved in cancer cell survival, potentially offering a fresh angle in tackling resistant cancer cells. Venetoclax, on the other hand, works by targeting and inhibiting the BCL-2 protein, which helps cancer cells live longer than they should. The combination of these two mechanisms could provide a powerful one-two punch against cancer cells, offering hope for more effective treatment with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

Research has shown that voruciclib, one of the treatments in this trial, holds promise for treating patients with acute myeloid leukemia (AML) when used alone. In earlier studies, one patient reached a point where no leukemia cells were found in their blood, and several patients maintained stable disease, meaning their condition did not worsen.

In this trial, some participants will receive voruciclib combined with venetoclax. Previous studies have shown even more encouraging results with this combination, effectively fighting leukemia cells and proving generally safe for patients with AML. Importantly, it did not cause additional side effects, making it a potential treatment option for those whose disease has returned or hasn't responded to other treatments. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain B-cell malignancies or AML that have not responded to at least two prior treatments. Eligible participants must have a confirmed diagnosis of specific lymphomas or leukemia, measurable disease, and adequate organ function. People with significant heart disease, uncontrolled HIV/AIDS, recent transplants, ongoing infections, or those on certain medications are excluded.

Inclusion Criteria

My kidney and liver tests are within normal ranges.

My cancer can be measured by specific guidelines.

I have been diagnosed with a specific type of blood cancer.

Exclusion Criteria

My CLL has transformed into an aggressive type of lymphoma.

Significant screening ECG abnormalities

My leukemia is of the acute promyelocytic type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Open-label, 3 + 3 dose escalation study to determine the safety and preliminary efficacy of voruciclib monotherapy or in combination with venetoclax

Variable, up to 2 years

Treatment

Participants receive voruciclib monotherapy or voruciclib in combination with venetoclax

Variable, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax
• Voruciclib

Trial Overview The study is testing the safety and potential effectiveness of voruciclib alone or combined with venetoclax in patients whose B-cell malignancy or AML has relapsed after standard therapies. It's an early-phase trial where dosages will be adjusted to find safe levels while monitoring how well the drugs work against these cancers.

How Is the Trial Designed?

Group I: voruciclib monotherapy and voruciclib in combination with venetoclax Experimental Treatment 2 Interventions

voruciclib monotherapy - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level and disease type (AML or B-cell malignancies) voruciclib and venetoclax - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level for AML subjects

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?

MEI Pharma, Inc.

Lead Sponsor

Trials

14

Recruited

860+

Published Research Related to This Trial

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]

In a study involving 272 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), higher concentrations of venetoclax led to a quicker reduction in lymphocyte counts and tumor size, resulting in a high objective response rate (ORR) of 84.8% at a daily dose of 400 mg.

Importantly, increasing the dose of venetoclax did not correlate with a higher risk of serious adverse events like neutropenia or infections, suggesting that the 400 mg daily regimen is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. Freise, KJ., Jones, AK., Eckert, D., et al.[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]

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]

Venetoclax is an effective and well-tolerated treatment for advanced hematological malignancies, particularly in patients with chronic lymphocytic leukemia, showing a satisfactory overall event rate of 73%.

The most common adverse events associated with venetoclax include nausea, diarrhea, and thrombocytopenia, but these are generally mild and manageable, with few cases of severe complications like tumor lysis syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bcl-2 Inhibitor Venetoclax in Hematological Malignancy: A Systematic Review and Meta-Analysis of Clinical Trials. Li, Q., Cheng, L., Shen, K., et al.[2020]

The combination of venetoclax with rituximab showed remarkable efficacy and a manageable safety profile in treating chronic lymphocytic leukemia (CLL), both in relapsed/refractory cases and as a first-line therapy for high-risk patients.

Similarly, the combination of ibrutinib with venetoclax also demonstrated striking efficacy, suggesting that these combinations could become new standard treatment options for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. Wanner, D., Steurer, M.[2020]

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]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/4/820/534793/A-phase-1-study-of-the-CDK9-inhibitor-voruciclib

A phase 1 study of the CDK9 inhibitor voruciclib in relapsed ... In AML, 1 patient achieved a morphologic leukemia-free state, and 2 had stable disease. Voruciclib treatment led to a decrease in MCL1 messenger ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924007389

A phase 1 study of the CDK9 inhibitor voruciclib in ... Voruciclib administered on days 1 to 14 in 28-day cycles was well tolerated with no DLT up to the target dose of 200 mg.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12343358/

The oral CDK9 inhibitor voruciclib combined with ... Voruciclib combined with venetoclax was well tolerated and achieved objective responses in patients with AML and prior venetoclax.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03547115

NCT03547115 | A Study of Voruciclib Alone or in ... This is a Phase 1, open-label, 3 + 3 dose escalation and expansion study to determine the safety and preliminary efficacy of voruciclib monotherapy in subjects ...

5. investor.meipharma.com investor.meipharma.com/news-releases/news-release-details/mei-pharma-reports-clinical-data-oral-cdk9-inhibitor-voruciclib

MEI Pharma Reports Clinical Data on Oral CDK9 Inhibitor ... In the 21 patients enrolled with AML, 1 patient at 100 mg achieved a morphologic leukemia-free state and 9 patients had disease stabilization, ...

6. nature.com nature.com/articles/s41598-017-18368-w

Voruciclib, a clinical stage oral CDK9 inhibitor, represses ... Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition.

7. investor.meipharma.com investor.meipharma.com/news-releases/news-release-details/mei-pharma-reports-update-clinical-study-evaluating-oral-cdk9

MEI Pharma Reports Update from Clinical Study Evaluating ... “When Voruciclib is used in combination with venetoclax, the combination appears to have no added toxicity, in addition there is evidence of ...