Cirmtuzumab Consolidation for Chronic Lymphocytic Leukemia

(Venetoclax Trial)

Overseen By Betty Cabrera, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must be taking: Venetoclax

Must not be taking: Steroids, Biologics, Chemotherapy, others

Disqualifiers: Infections, Hepatitis, Cirrhosis, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 6-12 months

5 Participants Needed

Trial Summary

What is the purpose of this trial?

Single center, open-label, phase 2 study to determine the efficacy of cirmtuzumab consolidation in patients with measurable disease on venetoclax.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must not take certain cancer treatments like steroids, biologic agents, or chemotherapy shortly before starting the trial. You can continue taking venetoclax if you are already on it.

What data supports the effectiveness of the drug Venetoclax for treating Chronic Lymphocytic Leukemia?

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 and providing longer progression-free survival when combined with other treatments. It is approved for use in several countries and has a manageable safety profile. ^{1 2 3 4 5}

Is Cirmtuzumab (Venetoclax) safe for humans?

Venetoclax, also known as Venclexta or Venclyxto, has been shown to have an acceptable safety profile in patients with chronic lymphocytic leukemia (CLL). Common side effects include neutropenia (low white blood cell count), but these can be managed with supportive care and dose adjustments. ^{1 2 4 5 6}

What makes the drug venetoclax unique for treating chronic lymphocytic leukemia?

Venetoclax is unique because it is a first-in-class, oral drug that selectively inhibits B cell lymphoma-2 (BCL-2), a protein that helps cancer cells survive. It offers a chemotherapy-free option with a convenient once-daily regimen and has shown effectiveness in both relapsed/refractory and previously untreated chronic lymphocytic leukemia, even in patients with high-risk factors. ^{1 2 3 5 7}

Research Team

Benjamin M Heyman, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for patients with chronic lymphocytic leukemia (CLL) who still have detectable disease after at least 12 months on venetoclax. They must not have significant uncontrolled conditions or infections, and women cannot be pregnant or breastfeeding. Those recently treated with certain therapies or having another malignancy may be excluded.

Inclusion Criteria

I stopped taking venetoclax over 6 months ago and my cancer is considered low risk.

My blood test shows more than 0.01% leukemia cells.

I am currently taking venetoclax.

Exclusion Criteria

Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: uncontrolled and/or active systemic infection (viral, bacterial or fungal), chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate, Child class B or C cirrhosis, treatment with any of the following within 7 days prior to the first dose of cirmtuzumab: steroid therapy for anti-neoplastic intent, biologic agent (monoclonal antibody) within 30 days for anti-neoplastic intent, chemotherapy (purine analog or alkylating agent) or target small molecule agent within 14 days or 5 half-lives (whichever is shorter), or has not recovered to less than CTCAE grade 2 clinically significant adverse effect(s)/toxicity(s) of previous therapy, CLL therapy, aside from venetoclax, history of other malignancy that could affect compliance with the protocol or interpretation of results (example: patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible), women who are pregnant or lactating

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cirmtuzumab and venetoclax for a minimum of 6 cycles (28 days per cycle) as consolidation therapy

6-12 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

6-12 months

Treatment Details

Interventions

• Cirmtuzumab
• Venetoclax

Trial Overview The study is testing the effectiveness of cirmtuzumab given to patients who are already taking venetoclax but still show signs of CLL. It's a phase 2 trial where all participants will receive cirmtuzumab to see if it can further reduce leukemia cells.

Participant Groups

Group I: Cirmtuzumab + Venetoclax Experimental Treatment 2 Interventions

All patients will receive a minimum of 6 cycles (cycle = 28 days) of therapy with venetoclax and cirmtuzumab during the treatment period. For patients who achieve undetectable minimal residual disease (uMRD) positive after cycle 6, an additional 6 cycles of venetoclax and cirmtuzumab may be administered.

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 California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Oncternal Therapeutics, Inc

Industry Sponsor

Trials

7

Recruited

240+

Findings from Research

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 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]

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 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 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]

The combination of venetoclax and obinutuzumab was found to be safe and well-tolerated in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia, with no dose-limiting toxicities observed during the study.

The treatment resulted in a high overall response rate of 95% in relapsed/refractory patients and 100% in previously untreated patients, with significant rates of undetectable minimal residual disease, indicating effective disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Flinn, IW., Gribben, JG., Dyer, MJS., et al.[2021]

References

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

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

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

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

3. Austria pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia at ASH 2017. [2020]

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

Venetoclax: First Global Approval. [2018]

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

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

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

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Successful treatment of relapsed chronic lymphocytic leukemia with venetoclax in a patient with severe chronic kidney disease. [2022]