TERN-701 for Leukemia

Recruiting at 40 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Terns, Inc.

Must not be taking: Antineoplastics, Chemotherapy

Disqualifiers: Systemic therapy, Unresolved toxicity, others

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

Compensation: Varies

Number of Visits: 2

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic antineoplastic therapy (cancer treatment) at least 7 days before starting TERN-701. This includes prior TKIs, interferon-alfa, therapeutic antibodies, and chemotherapy.

What safety data exists for TERN-701 or similar treatments in humans?

The research on mitoxantrone, a treatment for leukemia, shows it can cause side effects like bone marrow suppression (reduced blood cell production), mucositis (mouth sores), and hair loss, but no heart damage was observed in short trials. Cytarabine, another leukemia treatment, can cause side effects like bone marrow suppression, fever, and skin reactions, among others. ^{1 2 3 4 5}

What is the purpose of this trial?

The goal of the study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TERN-701, a novel highly selective allosteric inhibitor of BCR-ABL1, in participants with previously treated chronic phase - chronic myeloid leukemia (CP-CML). The study has two parts: Part 1 of the trial (Dose Escalation) will evaluate sequential dose escalation cohorts of TERN-701 administered once daily. Part 2 (Dose Expansion) consists of randomized, parallel dose expansion cohorts of TERN-701 that will further evaluate the efficacy and safety of at least 2 recommended dose levels for expansion selected from Part 1. In both Part 1 and Part 2, participants will receive continuous daily dosing of TERN-701 divided into 28-day cycles. During the treatment period, participants will have scheduled visits to the trial center at Cycle 1 day 1(C1D1), C1D2, C1D8, C1D15, and C1D16, followed by Day 1 of Cycles 2 through 7, and Day 1 of every 3 cycles thereafter. Approximately 100 participants could be enrolled in this trial, including up to 60 participants in Part 1 (dose escalation), including optional backfill cohorts, and approximately 40 participants in Part 2 (randomized dose expansion). All participants will receive active trial intervention. At least 4 dose-level cohorts may be evaluated in Part 1; at least 2 dose levels may be evaluated in Part 2.

Eligibility Criteria

This trial is for adults over 18 with chronic myeloid leukemia who've had issues with previous treatments like intolerance or inadequate response. They should be relatively active (able to walk and do light activities), have their major organs working well, and not be in the advanced stages of leukemia.

Inclusion Criteria

My organs are working well, according to tests.

My leukemia is confirmed to be BCR-ABL1 positive in the chronic phase.

I have had a poor response or intolerance to targeted cancer therapy.

Exclusion Criteria

I haven't taken cancer drugs or been in a trial for at least 7 days.

My leukemia is in an advanced stage.

I still experience side effects from cancer treatment, but they are mild.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 of the trial will evaluate sequential dose escalation cohorts of TERN-701 administered once daily.

28-day cycles

Visits on C1D1, C1D2, C1D8, C1D15, C1D16, and Day 1 of Cycles 2-7

Dose Expansion

Part 2 consists of randomized, parallel dose expansion cohorts of TERN-701 to evaluate efficacy and safety.

28-day cycles

Visits on C1D1, C1D2, C1D8, C1D15, C1D16, and Day 1 of Cycles 2-7

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

Treatment Details

Interventions

• TERN-701

Trial Overview TERN-701, a new drug aimed at treating chronic myeloid leukemia, is being tested. The study has two parts: first, finding the right dose by increasing it gradually; second, giving more people this chosen dose to see how effective and safe it is when taken daily in cycles of 28 days.

Participant Groups

Group I: Part 2 - Dose 2 Experimental Treatment 1 Intervention

Dose 2 will be selected from Part 1 based on the totality of safety, PK, PD and efficacy data from Part 1 will be selected. TERN-701 is planned to be administered once daily.

Group II: Part 2 - Dose 1 Experimental Treatment 1 Intervention

Dose 1 will be selected from Part 1 based on the totality of safety, PK, PD and efficacy data from Part 1 will be selected. TERN-701 is planned to be administered once daily.

Group III: Part 1- Dose Level 4 of TERN-701 Experimental Treatment 1 Intervention

Dose Level 4 of TERN-701 dosed once daily.

Group IV: Part 1- Dose Level 3 of TERN-701 Experimental Treatment 1 Intervention

Dose Level 3 of TERN-701 dosed once daily.

Group V: Part 1- Dose Level 2 of TERN-701 Experimental Treatment 1 Intervention

Dose Level 2 of TERN-701 dosed once daily.

Group VI: Part 1- Dose Level 1 of TERN-701 Experimental Treatment 1 Intervention

Dose Level 1 of TERN-701 dosed once daily.

Who Is Running the Clinical Trial?

Terns, Inc.

Lead Sponsor

Trials

5

Recruited

570+

Findings from Research

In a study of 24 patients with acute leukemia or blast crisis of chronic myelocytic leukemia, mitoxantrone treatment led to complete remission in 5 out of 20 evaluable patients, indicating its potential efficacy in this challenging patient population.

While mitoxantrone caused moderate to severe side effects like bone marrow suppression and mucositis, it did not result in cardiotoxicity, suggesting a relatively safe profile for further investigation in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone in the treatment of relapsed and refractory acute leukemia. Meyer, P., Ho, AD., Ehninger, G., et al.[2019]

Mitoxantrone was administered to 40 patients with relapsed and refractory acute leukemia, showing promising results with complete and partial remissions, particularly in acute non-lymphocytic leukemia, where 4 complete and 6 partial remissions were observed.

The treatment was generally well-tolerated, with expected side effects like bone marrow depression and mild gastrointestinal symptoms, suggesting that mitoxantrone could be a safe and effective option for further studies in acute leukemia therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II trial of mitoxantrone in patients with relapsed and refractory acute leukemia]. Sampi, K., Ogawa, M., Kimura, I., et al.[2013]

Cytarabine is an effective treatment for hematological malignancies like acute leukemias and lymphomas, but it has a range of dose-dependent side effects, including serious conditions like bone marrow suppression and cardiomyopathy.

The abstract highlights three cases of delayed hypersensitivity reactions to cytarabine, specifically affecting the ears, which are believed to be linked to cytokine release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytarabine ears - A side effect of cytarabine therapy. Doval, D., Kumar Sharma, S., Kumar, M., et al.[2020]

Mitoxantrone, a synthetic drug used in treating acute leukemia, showed a 48% overall response rate and a 25% complete remission rate in a five-day treatment regimen, indicating its potential effectiveness.

The drug demonstrated limited toxicity compared to traditional anthracycline antibiotics, with only mild side effects like alopecia and nausea, although the short duration of trials did not allow for assessment of cardiac toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone in relapsed and refractory acute leukemia. Prentice, HG., Robbins, G., Ma, DD., et al.[2018]

Two specific genetic variants (SNPs) rs2025501 and rs6661575 were found to increase sensitivity to cytarabine and were linked to higher treatment-related mortality (TRM) in children with acute myeloid leukemia (AML), particularly when treated with high doses of cytarabine.

The study identified another SNP, rs17202778, which significantly impacts TRM, suggesting that these genetic markers could help predict patient responses to cytarabine and guide treatment decisions in future AML trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children's Oncology Group. Phillips, CL., Lane, A., Gerbing, RB., et al.[2021]

References

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

Mitoxantrone in the treatment of relapsed and refractory acute leukemia. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

[Phase II trial of mitoxantrone in patients with relapsed and refractory acute leukemia]. [2013]

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

Cytarabine ears - A side effect of cytarabine therapy. [2020]

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

Mitoxantrone in relapsed and refractory acute leukemia. [2018]

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

Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children's Oncology Group. [2021]