Venetoclax + Omacetaxine for Blood Cancer

(VEN-OM Trial)

Overseen By Kristen Kitsch, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Illinois at Chicago

Must be taking: Venetoclax

Must not be taking: CYP3A inducers/inhibitors

Disqualifiers: HIV, CNS AML, CHF, others

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

Compensation: Varies

Number of Visits: 5

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This will be a single arm, open label Phase Ib dose-escalation study of the combination of VEN and OM, conducted using an innovative Bayesian Optimal Interval-design, to find the MTD in participants with AML failing treatment with venetoclax-containing regimens. Treatment plan will consist of an induction phase, followed by a consolidation phase if applicable.

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 stop taking Hydroxyurea at least 48 hours before registration. Also, you cannot have taken strong or moderate CYP3A inducers or inhibitors within 7 days before starting the study treatment.

How is the drug combination of Venetoclax and Omacetaxine unique for treating blood cancer?

The combination of Venetoclax and Omacetaxine is unique because Venetoclax specifically targets and blocks a protein called BCL-2, which helps cancer cells survive, while Omacetaxine works by interfering with the production of proteins necessary for cancer cell growth. This dual approach may offer a novel way to treat blood cancers by attacking the cancer cells from two different angles. ^{1 2 3 4 5}

Research Team

John G. Quigley

Principal Investigator

University of Illinois at Chicago

Eligibility Criteria

Adults aged 18-75 with Acute Myeloid Leukemia (AML) that has returned or didn't respond to treatment, including a regimen with Venetoclax. Participants must have finished previous cancer treatments at least 21 days before and recovered from their effects, be able to perform daily activities with minimal assistance (ECOG score 0-2), not be pregnant or breastfeeding, agree to use contraception, and have adequate organ function.

Inclusion Criteria

Females of childbearing potential and males must be willing to use effective contraception during treatment and for at least 30 days after the last dose of Venetoclax

I finished my last cancer treatment over 3 weeks ago and have recovered from its side effects.

My kidney and liver functions are within the required range.

Exclusion Criteria

Pregnant or breastfeeding

I do not have any severe or uncontrolled infections.

I do not have any severe health or mental conditions that could make this study risky for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Treatment

Participants receive Omacetaxine and Venetoclax with dose escalation to find the MTD

4 weeks per cycle

Day 1 and Day 28 of each cycle (in-person)

Consolidation Treatment

Participants may receive additional cycles of treatment if applicable

4 weeks per cycle

Safety Follow-up

Participants are monitored for safety 14 days after the last dose of treatment

2-3 weeks

1 visit (in-person)

Long Term Follow-up

Participants are monitored every 2 months for 12 months for long-term safety and survival outcomes

12 months

Every 2 months (in-person)

Treatment Details

Interventions

• Omacetaxine
• Venetoclax

Trial Overview The trial is testing the safety and effectiveness of combining two drugs: Venetoclax and Omacetaxine in escalating doses for AML patients who haven't responded well to previous treatments. It's an open-label study where everyone gets the same treatment, starting with induction then consolidation phases if needed.

Participant Groups

Group I: Cohort 4 Experimental Treatment 2 Interventions

Omacetaxine 2.5 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Group II: Cohort 3 Experimental Treatment 2 Interventions

Omacetaxine 2.0 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Group III: Cohort 2 Experimental Treatment 2 Interventions

Omacetaxine 1.25 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Group IV: Cohort 1 Experimental Treatment 2 Interventions

Omacetaxine 0.625 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Omacetaxine is already approved in United States, European Union for the following indications:

Approved in United States as Synribo for:

• Chronic myeloid leukemia (CML), accelerated phase
• Chronic myeloid leukemia (CML), blast phase

Approved in European Union as Synribo for:

• Chronic myeloid leukemia (CML), accelerated phase
• Chronic myeloid leukemia (CML), blast phase

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Findings from Research

In a phase II trial involving 46 patients with untreated metastatic colorectal cancer, the combination of irinotecan and raltitrexed showed a promising overall response rate of 46%, indicating significant efficacy in this patient population.

While the treatment was effective, it also presented notable toxicities, including severe diarrhea in 26% of patients and neutropenia in 20%, suggesting that while the regimen is active, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan and raltitrexed: an active combination in advanced colorectal cancer. Carnaghi, C., Rimassa, L., Garassino, I., et al.[2020]

In a study of 94 patients aged 70 and older with advanced colorectal cancer, both CAPOX and CAPIRI treatments showed similar overall response rates (38% for CAPOX and 36% for CAPIRI), indicating comparable efficacy as first-line treatments.

CAPOX was better tolerated than CAPIRI, with fewer severe side effects such as diarrhea and neutropenia, suggesting it may be a safer option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. Rosati, G., Cordio, S., Bordonaro, R., et al.[2020]

The XELOX30 regimen, which combines capecitabine and a shorter 30-minute infusion of oxaliplatin, was tested in 70 patients with advanced colorectal cancer resistant to irinotecan, showing a response rate of 17% and a median survival of 9.5 months.

The treatment demonstrated a moderate level of neurotoxicity, with 56% of patients experiencing grade 1 and 17% grade 2 neuropathy, indicating that XELOX30 is a convenient and effective second-line therapy with a safety profile comparable to longer infusion schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil. Pfeiffer, P., Sørbye, H., Ehrsson, H., et al.[2020]

Premetrexed disodium (MTA) shows promising anti-proliferative effects against colon cancer, especially when combined with oxaliplatin or SN38, demonstrating synergistic activity in both standard and 5-fluorouracil-resistant cancer cells.

The combination of MTA with oxaliplatin resulted in additive antitumor effects with minimal toxicity in mouse models, suggesting a potential for safer and more effective chemotherapy regimens for colon cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed disodium combined with oxaliplatin, SN38, or 5-fluorouracil, based on the quantitation of drug interactions in human HT29 colon cancer cells. Raymond, E., Louvet, C., Tournigand, C., et al.[2018]

In a phase II trial involving 48 patients with untreated advanced colorectal cancer, the combination of irinotecan and raltitrexed showed an overall response rate of 27%, with a median duration of response of 10 months.

Despite its activity, the treatment was associated with significant side effects, including grade III-IV diarrhea and neutropenia, leading to a dose reduction and highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer. Chiara, S., Nobile, MT., Tomasello, L., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Irinotecan and raltitrexed: an active combination in advanced colorectal cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. [2020]

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

Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil. [2020]

4. Greece pubmed.ncbi.nlm.nih.gov

Pemetrexed disodium combined with oxaliplatin, SN38, or 5-fluorouracil, based on the quantitation of drug interactions in human HT29 colon cancer cells. [2018]

5. Greece pubmed.ncbi.nlm.nih.gov

Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer. [2018]