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

Trial Summary

What is the purpose of this trial?

A study to assess the effect of multiple doses of venetoclax on the pharmacokinetics of ethinyl estradiol and levonorgestrel in female participants with different hematological malignancies. Upon completion of this study, participants receiving clinical benefit in the opinion of the investigator and without any clinically significant evidence of disease progression with no access to venetoclax (not approved for the treated indication) may continue receiving venetoclax at the discretion of the investigator in a separate extension study.

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.

What makes Venetoclax unique for treating blood cancers?

Venetoclax is unique because it specifically targets and inhibits a protein called BCL-2, which helps cancer cells survive, making it different from traditional chemotherapy that targets rapidly dividing cells. This targeted approach can lead to fewer side effects and is particularly effective in certain types of blood cancers where BCL-2 is overexpressed. ^{1 2 3 4 5}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

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

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. [2019]

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

Studies of the efficacy and pharmacology of irinotecan against human colon tumor xenograft models. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Sensitive HPLC-fluorescence method for irinotecan and four major metabolites in human plasma and saliva: application to pharmacokinetic studies. [2019]

4. United States 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. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Disposition of irinotecan and SN-38 following oral and intravenous irinotecan dosing in mice. [2018]