Venetoclax for Blood Cancers

Recruiting at 1 trial location

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: AbbVie

Disqualifiers: Cardiovascular disease, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how venetoclax, a drug for treating blood cancers, affects other medications in women with certain blood cancers. The goal is to determine if venetoclax alters how the body processes ethinyl estradiol and levonorgestrel, common components in birth control pills. Women with relapsed or hard-to-treat forms of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma or follicular lymphoma, may qualify if their cancer has returned or hasn't responded to treatment. Participants should also be able to perform daily activities without significant difficulty. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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 trial team or your doctor.

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

Research shows that venetoclax is generally well-tolerated by people with blood cancers. In a study of patients with relapsed or hard-to-treat non-Hodgkin lymphoma (a type of blood cancer), venetoclax alone proved safe to use. Some patients responded well to the treatment, indicating potential effectiveness.

However, like many treatments, venetoclax can cause side effects. Commonly reported side effects include low white blood cell counts, which can increase infection risk. Despite these concerns, research suggests the treatment is mild and effective for advanced blood cancers.

Although this trial also involves ethinyl estradiol and levonorgestrel, the main focus is on venetoclax's safety. This is an early-stage study, meaning less safety data is available compared to later stages. Still, existing studies provide some reassurance about venetoclax's safety in similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Venetoclax for blood cancers because it works differently from many current treatments. Most standard treatments for blood cancers, like chemotherapy, generally target rapidly dividing cells, impacting both cancerous and healthy cells. Venetoclax, however, specifically targets the B-cell lymphoma-2 (BCL-2) protein, which helps cancer cells survive. By inhibiting BCL-2, Venetoclax encourages the cancer cells to undergo programmed cell death, potentially leading to more effective and targeted treatment with fewer side effects. This targeted approach could offer new hope for patients with blood cancers, providing a more refined method of attack against the disease.

What evidence suggests that venetoclax might be an effective treatment for blood cancers?

Research has shown that venetoclax, which participants in this trial may receive, holds promise for treating various blood cancers. Studies have found that about 15% of patients respond to the treatment, with some experiencing complete remission, meaning their cancer was not detectable after treatment. In one study, tumors treated with venetoclax exhibited high levels of activity, indicating cancer cell death. While more research is needed, these findings suggest that venetoclax could be an effective option for people with blood cancers. ^{2 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for women with certain blood cancers like non-Hodgkin's lymphoma who have tried other treatments without success. They should be relatively active (ECOG score ≤2) and have good organ function. Women must not be able to bear children, haven't had a stem cell transplant in the last 100 days, no brain involvement by lymphoma, no serious heart disease or recent transformation of their cancer.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I cannot become pregnant.

I have been diagnosed with a specific type of non-Hodgkin lymphoma.

Exclusion Criteria

I have a serious heart condition that is currently active.

Evidence of transformation of the lymphoma immediately prior to study entry

My lymphoma has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of venetoclax and ethinyl estradiol/levonorgestrel to assess pharmacokinetics

8 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue receiving venetoclax if they are benefiting and have no disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Ethinyl Estradiol/Levonorgestrel
• Venetoclax

Trial Overview The study tests how multiple doses of Venetoclax affect the levels of birth control hormones ethinyl estradiol and levonorgestrel in women with various blood cancers. Participants benefiting from Venetoclax may continue treatment under an extension study after this one ends.

How Is the Trial Designed?

Group I: Ethinyl estradiol/Levonorgestrel and Venetoclax Experimental Treatment 2 Interventions

Ethinyl estradiol/levonorgestrel is administered on Period 1 Day 1 and then again on Period 3 Day 1. Venetoclax is administered on Period 2 Day 1 and then daily thereafter.

Ethinyl Estradiol/Levonorgestrel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ethinyl Estradiol/Levonorgestrel for:

• Birth control
• Menstrual regulation
• Premenstrual dysphoric disorder

Approved in European Union as Ethinyl Estradiol/Levonorgestrel for:

• Contraception
• Premenstrual dysphoric disorder

Approved in Canada as Ethinyl Estradiol/Levonorgestrel for:

• Birth control
• Menstrual regulation

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

Irinotecan lactone shows a biphasic plasma disposition with a terminal half-life of 1.1 to 3 hours after intravenous administration, indicating its pharmacokinetics can vary significantly with dosage.

Oral administration of irinotecan lactone results in low bioavailability (0.12 at 10 mg/kg and 0.21 at 40 mg/kg), but systemic exposure to its active metabolite, SN-38 lactone, is higher in tumor-bearing mice, suggesting enhanced efficacy in a therapeutic context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disposition of irinotecan and SN-38 following oral and intravenous irinotecan dosing in mice. Stewart, CF., Zamboni, WC., Crom, WR., et al.[2018]

Combining irinotecan hydrochloride (SN-38) with cisplatin significantly enhances the anticancer effects against colorectal cancer, as shown by a study using freshly isolated cancer cells from 20 patients.

The study found that even at lower concentrations, the combination of SN-38 and cisplatin produced a strong synergistic effect, suggesting a promising strategy for improving chemotherapy outcomes in advanced colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. Tsunoda, T., Tanimura, H., Hotta, T., et al.[2019]

Oral administration of irinotecan showed similar efficacy to intravenous administration against various human colon carcinoma xenografts, achieving complete responses in five out of seven tested lines, particularly at higher doses.

The study found that oral irinotecan resulted in significantly higher systemic exposure of its active metabolite, SN-38, compared to intravenous administration, suggesting that oral dosing could be an effective alternative for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies of the efficacy and pharmacology of irinotecan against human colon tumor xenograft models. Zamboni, WC., Stewart, CF., Cheshire, PJ., et al.[2018]

A new gradient HPLC method was developed to accurately measure the levels of irinotecan and its metabolites in human plasma and saliva, which is crucial for understanding the drug's pharmacokinetics in patients with metastatic colorectal cancer.

The assay demonstrated high sensitivity and reliability, with limits of quantification as low as 0.5 micro g/L and good recovery rates, making it a valuable tool for monitoring drug levels and optimizing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitive HPLC-fluorescence method for irinotecan and four major metabolites in human plasma and saliva: application to pharmacokinetic studies. Poujol, S., Pinguet, F., Malosse, F., et al.[2019]

In a study of 51 patients with advanced or recurrent squamous cell carcinoma of the cervix, the combination of irinotecan (CPT-11) and mitomycin-C (MMC) resulted in an overall response rate of 51%, with a higher rate of 76% in patients receiving it as neoadjuvant chemotherapy.

While the treatment showed promising efficacy, it also had significant toxicity, with 59% of patients experiencing severe neutropenia and 12% experiencing severe diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of irinotecan combined with mitomycin-C for advanced or recurrent squamous cell carcinoma of the uterine cervix: the JGOG study. Umesaki, N., Fujii, T., Nishimura, R., et al.[2018]

Citations

1. ashpublications.org ashpublications.org/blood/article/126/23/254/112989/A-Phase-1-Study-of-Venetoclax-ABT-199-GDC-0199

A Phase 1 Study of Venetoclax (ABT-199 / GDC-0199 ... The overall response rate (ORR) was 15% [3 (9%) CR and 2 (6%) PR] for pts with DLBCL (n=34). The median duration of response for DLBCL was 3.3 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4618648/

Clearance of systemic hematologic tumors by venetoclax (Abt ... By 24 h, navitoclax-treated tumors had reached 80% caspase positivity, while caspase staining was seen in 99% of venetoclax-treated tumors. VivoGlo imaging ...

3. news.abbvie.com news.abbvie.com/2014-12-07-AbbVie-Presents-Results-from-Phase-2-Study-of-Investigational-Compound-Venetoclax-ABT-199-GDC-0199-in-Acute-Myelogenous-Leukemia-at-the-56th-American-Society-of-Hematology-Annual-Meeting

Study Evaluated Preliminary Efficacy of Venetoclax in 32 ... In the study, the venetoclax group showed an overall response rate (ORR) of 15.5 percent, with one patient achieving a complete response and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118472333

A Phase 1 Study of Venetoclax (ABT-199 / GDC-0199) ... Conclusions: Venetoclax monotherapy demonstrated a tolerable safety profile in pts with R/R NHL. Several pts with DLBCL had an initial response ...

5. venclextahcp.com venclextahcp.com/cll/efficacy/ven-g/data.html

VENCLEXTA efficacy results: 6-year overall survival 1 In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with ...

6. venclextahcp.com venclextahcp.com/cll/side-effects/ven-g-safety-profile.html

VEN+G Safety Data for CLL/SLL - venclexta In the VEN+G arm, adverse reactions led to treatment discontinuation in 16% of patients, dose reduction in 21%, and dose interruption in 74% · Neutropenia led to ...

7. ashpublications.org ashpublications.org/bloodadvances/article/8/4/857/506893/Risk-of-infectious-adverse-events-of-venetoclax

Risk of infectious adverse events of venetoclax therapy for ... Risk of infectious adverse events of venetoclax therapy for hematologic malignancies: a systematic review and meta-analysis of RCTs

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6598635/

Efficacy and Safety of Bcl-2 Inhibitor Venetoclax in ... After analysis of the data, we found that venetoclax is a mild and efficient drug in treating advanced hematological malignancy that is ...

9. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/20/NCT02055820/Prot_002.pdf

A Phase IB/II, Open-Label Study Evaluating the Safety and Toxicology assessments completed to date with venetoclax are general toxicology studies with periods of once-daily oral dosing ranging from 2 weeks to 6 months ...