ELVN-001 for Chronic Myelogenous Leukemia

(CML Trial)

Recruiting at 28 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Enliven Therapeutics

Must not be taking: Anti-cancer, Anti-CML

Disqualifiers: Pancreatitis, QTc >470 ms, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called ELVN-001 for safety and effectiveness in patients with chronic myeloid leukemia who have not had success with other treatments. The drug aims to reduce cancer markers in the blood to better control the disease.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer or anti-CML medications at least 7 days before starting the study drug, or longer if the medication stays in your body for a while (5 half-lives).

What data supports the effectiveness of the drug ELVN-001 for chronic myelogenous leukemia?

The research highlights the success of tyrosine kinase inhibitors (TKIs) like imatinib, nilotinib, and dasatinib in improving survival rates for chronic myelogenous leukemia (CML). These drugs target the BCR-ABL protein, which is involved in CML, suggesting that similar mechanisms might support the effectiveness of ELVN-001 if it functions in a comparable way. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with chronic myeloid leukemia who have not responded well to, or cannot tolerate, current treatments. Participants should be relatively active (ECOG status 0-2) and have good blood, liver, and kidney function. Those with a recent history of cancer treatment or abnormal heart rhythm (QTc >470 ms) are excluded.

Inclusion Criteria

I can care for myself and am up and about more than 50% of my waking hours.

I have CML and cannot tolerate or haven't responded to current treatments.

My blood, liver, and kidney functions are all within normal ranges.

Exclusion Criteria

I haven't taken any cancer or CML medication in the last 7 days or 5 half-lives, whichever is longer.

QTc >470 ms

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ELVN-001 administered in 3+3 dose escalation to determine the recommended dose for expansion

4 weeks

Dose Expansion

ELVN-001 administered at the recommended dose in CML with and without T315I mutations

up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• ELVN-001 (Other)

Trial Overview The study is testing ELVN-001's safety and the right dose for people with chronic myeloid leukemia, including those with T315I mutations who haven't had success with tyrosine kinase inhibitors (TKIs).

Participant Groups

Group I: Phase 1b expansion arm in T315I mutated CML Experimental Treatment 1 Intervention

ELVN-001 administered at the recommended dose for CML with T315I mutation

Group II: Phase 1b Dose Expansion at recommended dose level 2 Experimental Treatment 1 Intervention

ELVN-001 administered at a different recommended dose in CML without T315I mutations

Group III: Phase 1b Dose Expansion at recommended dose level 1 Experimental Treatment 1 Intervention

ELVN-001 administered at the recommended dose in CML without T315I mutations

Group IV: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

ELVN-001 administered in 3+3 dose escalation

Who Is Running the Clinical Trial?

Enliven Therapeutics

Lead Sponsor

Trials

4

Recruited

670+

Findings from Research

In a study of 162 newly diagnosed chronic myeloid leukemia patients, combining escalated doses of imatinib with intravenous cytarabine resulted in high rates of treatment response, with 53% achieving a complete molecular response after 5 years.

The study found that higher doses of both imatinib and cytarabine were linked to better treatment outcomes, and the overall survival rate was an impressive 96%, indicating the effectiveness of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia. Deenik, W., Janssen, JJ., van der Holt, B., et al.[2022]

The updated European LeukemiaNet (ELN) recommendations emphasize the importance of regular monitoring for chronic myeloid leukemia (CML) patients, requiring cytogenetic assessments at 3, 6, 12, and 18 months, and molecular monitoring every 3 months to evaluate treatment response.

Imatinib at a dose of 400 mg daily remains the first-line treatment for CML, with options for second-generation tyrosine kinase inhibitors for patients who show suboptimal response or treatment failure, highlighting a structured approach to managing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. Baccarani, M., Cortes, J., Pane, F., et al.[2023]

The survival rates for early-phase chronic myelogenous leukemia (CML) have significantly improved due to the use of tyrosine kinase inhibitors (TKIs) like imatinib, nilotinib, and dasatinib.

Monitoring treatment response through complete cytogenetic response and mutational analysis is crucial for managing imatinib resistance, with new agents like ponatinib and bosutinib now available for resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring response to tyrosine kinase inhibitor therapy, mutational analysis, and new treatment options in chronic myelogenous leukemia. Radich, JP.[2019]

Imatinib, a targeted inhibitor of the BCR-ABL fusion protein, has significantly improved survival rates for patients with chronic myelogenous leukemia (CML), but some patients develop resistance or intolerance to this therapy.

Second-generation tyrosine kinase inhibitors like nilotinib and dasatinib, along with newer options like ponatinib and bosutinib, provide additional treatment choices for CML, enhancing patient outcomes and quality of life, and ongoing clinical trials are exploring the best ways to use these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy in chronic myelogenous leukemia: where do emerging therapies fit within current treatment regimens? Mauro, MJ., Talpaz, M., Radich, JP.[2017]

Recent advances in the treatment of chronic myeloid leukemia (CML) and BCR-ABL1-negative myeloproliferative neoplasms (MPNs) include updates on JAK2 inhibitors and the use of alpha interferons, which show promise in targeting these conditions.

The review highlights the importance of monitoring strategies and the potential for targeting CML stem cells and their niche, which could lead to more effective therapies and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary insights into the pathogenesis and treatment of chronic myeloproliferative neoplasms. Mughal, TI., Abdel-Wahab, O., Rampal, R., et al.[2019]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia. [2022]

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

Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. [2023]

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

Monitoring response to tyrosine kinase inhibitor therapy, mutational analysis, and new treatment options in chronic myelogenous leukemia. [2019]

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

Sequential therapy in chronic myelogenous leukemia: where do emerging therapies fit within current treatment regimens? [2017]

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

Contemporary insights into the pathogenesis and treatment of chronic myeloproliferative neoplasms. [2019]