Voruciclib + Venetoclax for Leukemia and Lymphoma

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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1, open-label, dose escalation study to determine the safety and preliminary efficacy of voruciclib monotherapy in subjects with relapsed/refractory B cell malignancies or AML after failure of standard therapies or voruciclib in combination with venetoclax in subjects with relapsed or refractory AML

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.

What data supports the effectiveness of the drug Venetoclax for leukemia and lymphoma?

Venetoclax has shown to be effective in treating chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in patients with relapsed or refractory CLL. It has also been effective in combination therapies, providing longer progression-free survival and higher rates of undetectable minimal residual disease compared to other treatments. ^{1 2 3 4 5}

Is the combination of Voruciclib and Venetoclax safe for treating leukemia and lymphoma?

Venetoclax has been shown to have an acceptable safety profile in treating chronic lymphocytic leukemia (CLL) and other blood cancers, with common side effects including nausea, diarrhea, and low blood cell counts. These side effects are generally manageable with supportive care and dose adjustments. ^{1 2 3 4 6}

What makes the drug combination of Voruciclib and Venetoclax unique for treating leukemia and lymphoma?

The combination of Voruciclib and Venetoclax is unique because Venetoclax is a first-in-class, oral drug that specifically targets and inhibits B-cell lymphoma 2 (BCL-2), a protein that helps cancer cells survive. This combination may offer a novel approach by potentially enhancing the effectiveness of Venetoclax in treating leukemia and lymphoma, especially in cases where other treatments have failed. ^{1 2 3 5 7}

Eligibility Criteria

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.

I am 18 years old or older.

My cancer can be measured by specific guidelines.

Exclusion Criteria

My CLL has transformed into an aggressive type of lymphoma.

My leukemia is of the acute promyelocytic type.

My cancer has spread to my brain or spinal cord.

Timeline

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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

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

Venetoclax: First Global Approval. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. [2018]

6. Switzerland 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. [2020]

7. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [2020]