LP-108 + Azacitidine for Leukemia

Not currently recruiting at 8 trial locations

Overseen By Anna Chen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Newave Pharmaceutical Inc

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers, Statins, others

Disqualifiers: Promyelocytic leukemia, Recent HSCT, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for certain blood cancers, including myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Researchers aim to determine if the new drug, LP-108, alone or with azacitidine, is safe and effective for patients whose cancer has returned or hasn't responded to other treatments. The trial consists of two parts: one tests different doses of LP-108 alone, and the other combines LP-108 with azacitidine. People with these cancers who haven't had success with standard therapies and experience frequent symptoms may be eligible to join. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new medication.

Do I need to stop my current medications for the trial?

You may need to stop certain medications before joining the trial. Specifically, you should not take strong CYP3A4 inhibitors, strong CYP3A4 inducers, P-gp and BCRP inhibitors, immunosuppressive drugs over 10mg prednisone, statins, systemic acid-reducing agents, and certain CYP2C8 substrates. There is a washout period for some medications, so it's best to discuss your current medications with the trial team.

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

Research has shown that LP-108, whether used alone or with azacitidine, is generally well tolerated by patients with certain blood cancers like MDS, CMML, and AML. Most participants did not experience severe side effects, and the treatment is considered to have an acceptable safety profile.

In the current early-stage trial (Phase 1), the main focus is on ensuring the treatment's safety and determining the best dose. Researchers are still learning about any possible side effects. The fact that LP-108 is being tested in humans suggests that earlier research indicated it might be safe enough for broader testing. Prospective participants should discuss details and concerns with a healthcare professional before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LP-108 for leukemia because it offers a fresh approach compared to standard treatments like chemotherapy. LP-108 is a novel oral medication that targets specific molecules involved in cancer cell growth, potentially leading to more precise treatment with fewer side effects. When combined with azacitidine, LP-108 may enhance effectiveness by working synergistically to tackle leukemia cells more aggressively. This combination could provide a more effective and potentially less toxic alternative to current therapies, sparking hope for improved outcomes in leukemia treatment.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that LP-108 may be a promising treatment for certain blood cancers. In studies involving patients with recurrent or treatment-resistant conditions, such as Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), and Acute Myeloid Leukemia (AML), LP-108 alone achieved a response rate of 54.5%. This indicates that more than half of the patients experienced a significant positive effect from the treatment. In this trial, some participants will receive LP-108 as monotherapy, while others will receive it in combination with azacitidine. Researchers continue to study specific results for this combination, but the positive responses suggest that LP-108, especially when combined with azacitidine, could be effective for patients with these challenging conditions. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced blood cancers like MDS, CMML, or AML that have come back or didn't respond to treatment. They should have functioning kidneys and liver, no serious heart issues, and a blast count under control. It's not for those who've had recent cancer treatments they haven't recovered from, stem cell transplants within the last 60 days, active brain involvement by leukemia, or are on strong drugs affecting liver enzymes.

Inclusion Criteria

My blood cancer cell count is low enough to start the trial treatment.

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

I have a severe type of anemia called RAEB or my MDS is high-risk and not responding to treatment.

Exclusion Criteria

I haven't had a fever over 38.5°C without a known cause during the screening or on the first day of the study drug.

I don't have active brain involvement from my cancer, or if I did, it's now under control.

I do not have active or uncontrolled HIV, hepatitis B, or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive sequentially higher oral doses of LP-108 on a once daily schedule for 28 days per cycle

4 weeks per cycle, up to 13 cycles

Dose Expansion

Participants receive LP-108 in combination with azacitidine on a once daily schedule for 28 days per cycle

4 weeks per cycle, up to 13 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LP-108
• LP-108 and Azacitidine

Trial Overview The study tests LP-108 alone and combined with azacitidine in pill form to see how safe it is and how well it works against specific blood cancers. The doses will be increased slowly to find the highest dose patients can take without bad side effects.

How Is the Trial Designed?

Group I: Dose Expansion Phase: LP-108 in combination with azacitidine Experimental Treatment 1 Intervention

Three to 6 subjects per treatment cohort will be assigned to receive sequentially higher oral doses of LP-108 on a once daily schedule for 28 days (a "Cycle") starting at a dose of 100 mg in combination with azacitidine at 75 mg/m2.

Group II: Dose Escalation Phase: LP-108 monotherapy Experimental Treatment 1 Intervention

Three to 6 subjects per treatment cohort will be assigned to receive sequentially higher oral doses of LP-108 on a once daily schedule for 28 days (a "Cycle") starting at a dose of 100 mg.

Who Is Running the Clinical Trial?

Newave Pharmaceutical Inc

Lead Sponsor

Trials

4

Recruited

270+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10429459/

SAFETY AND EFFICACY OF LP-108 AS MONOTHERAPY ... Across all dosing cohorts in Arm 2, the ORR was 54.5% (6 pts) and the remaining 5 pts (45.4%) experienced SD as best response (11 evaluable pts) ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.TPS7071

Phase 1 study of LP-108 as monotherapy and in ... We propose to investigate LP-108 as monotherapy and in combination with azacitidine in patients with relapsed or refractory (r/r) MDS, CMML or ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05641259

A Study to Assess Safety and Preliminary Efficacy of LP- ... This is a Phase 1, open-label, multicenter, dose-escalation & expansion study to evaluate the safety,tolerability and pharmacokinetics (PK) of LP-108, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124088372

A Phase 1, Multicenter, Open-Label, Dose-Escalation ... We explore the toxicity and tolerability of LP-108 as monotherapy and combined with azacitidine (Aza) in patients with relapse/refractory Acute Myeloid Leukemia ...

5. trialx.com trialx.com/clinical-trials/listings/249311/a-study-to-assess-safety-and-preliminary-efficacy-of-lp-108-combined-with-azacitidine-in-subjects-with-aml-mds-cmml/

A Study to Assess Safety and Preliminary Efficacy of LP ... This is a Phase 1, open-label, multicenter, dose-escalation & expansion study to evaluate the safety,tolerability and pharmacokinetics (PK) of ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS7071

Phase 1 study of LP-108 as monotherapy and in ... We propose to investigate LP-108 as monotherapy and in combination with azacitidine in patients with relapsed or refractory (r/r) MDS, CMML or AML.