LP-118 for Leukemia

Recruiting at 7 trial locations

Overseen By Anna Chen, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Newave Pharmaceutical Inc

Must not be taking: CYP3A inhibitors, CYP3A inducers, TdP drugs

Disqualifiers: Recent HSCT, Active malignancies, others

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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, LP-118, for individuals with various types of leukemia and related blood cancers. The main goal is to determine the safety of LP-118 and assess its tolerability when taken daily. The trial will explore different doses to identify the optimal one while monitoring for any potential effects on the body. Individuals with specific forms of leukemia or other blood cancers who have not responded to other treatments might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how LP-118 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does mention a 2-day washout period (time without taking certain medications) for some treatments like BCR antagonists and JAK2 antagonists. Additionally, certain medications, such as strong CYP3A inhibitors and inducers, should be avoided before starting the trial.

Is there any evidence suggesting that LP-118 is likely to be safe for humans?

Research has shown that LP-118, a treatment under study, has undergone safety testing in several studies. These studies found that LP-118 can trigger certain proteins in cancer cells, causing the cells to die. This finding is promising for its effectiveness, but what about safety?

Previous studies have examined how well people tolerate LP-118. Researchers begin with a low dose and gradually increase it to determine the safest and most effective amount. This approach helps manage any side effects and is a common method for testing new treatments.

In the current phase of testing, researchers focus primarily on safety. They closely monitor for any side effects and adjust doses as needed. So far, LP-118 has been considered safe enough to continue testing in humans. This process is crucial for identifying and managing any risks effectively. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

LP-118 is unique because it introduces a novel approach to treating leukemia by targeting specific pathways within cancer cells. Unlike traditional chemotherapy, which attacks both healthy and cancerous cells, LP-118 aims to minimize damage to normal cells, potentially reducing side effects. Researchers are excited about its ability to be fine-tuned in dosing, allowing for a more personalized treatment plan that adapts to the patient's needs. This precise targeting and adaptability could lead to more effective and safer treatment outcomes for leukemia patients.

What evidence suggests that LP-118 might be an effective treatment for leukemia?

Research has shown that LP-118 can help people with leukemia by increasing survival and slowing tumor growth. It targets specific cancer cells to control the disease. In lab studies, LP-118 proved effective against certain blood cancers, both alone and with standard treatments. Early tests on cell samples also showed promising results for chronic lymphocytic leukemia (CLL), suggesting potential effectiveness in these cases. Overall, these findings indicate that LP-118 might be a promising treatment option for leukemia, but more research is needed to confirm its effectiveness in people.

This trial will explore LP-118 in two phases: the Dose Escalation Phase, which tests different dosages to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), and the Dose Expansion Phase, which will further examine safety, tolerability, pharmacokinetics (PK), and efficacy in specific subgroups. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults with various advanced blood cancers like CLL, SLL, ALL, AML, and others who have tried at least one or two prior treatments without success can join this trial. It's also open to certain adolescents (13-18) with B cell ALL if they weigh over 40 kg. Participants need good heart function and adequate bone marrow, liver, and kidney function.

Inclusion Criteria

My condition is an advanced blood cancer.

Criterion: Participants with certain types of advanced or high-risk leukemia or lymphoma who have received several previous treatments and have specific levels of blood cells, heart function, bone marrow, blood clotting, kidney function, and liver function within normal ranges.

My CLL/SLL is low risk, progressed on BTK inhibitors, and I've had at least 2 prior treatments.

Exclusion Criteria

I haven't taken strong medication affecting liver enzymes or certain cancer treatments in the last 7 days.

Your heart's electrical activity is abnormal, or you have a heart condition that affects your daily activities.

I haven't had a stem cell transplant in the last 60 days and am not on strong immune system drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Phase

Phase 1a dose-escalation to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) using a 3+3 study design

Approximately 4-8 weeks

Dose Expansion Phase

Additional subjects recruited to further explore safety, tolerability, PK, and efficacy in specific subgroups

Approximately 36 cycles (each cycle is 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LP-118

Trial Overview LP-118 is an oral medication being tested in a Phase 1 clinical trial for safety and how the body processes it. The study has two parts: first finding the right dose (Phase 1a), then giving that dose to more people to learn more about its effects (Phase 1b).

How Is the Trial Designed?

Group I: Dose Expansion Phase Experimental Treatment 1 Intervention

Additional subjects will be recruited to further explore the safety, tolerability, PK, and efficacy in specific subject subgroups. One or more RP2D may be explored. Definition of these cohorts will be accomplished by protocol amendment, and in light of emerging data from Phase 1a.

Group II: Dose Escalation Phase Experimental Treatment 1 Intervention

Phase 1a dose-escalation will begin with group 1 and proceed until DLT is observed and MTD is established, or until an RP2D is established. Subjects enrolled in the dose cohorts will follow the 3+3 study design, starting with an accelerated step-up dosing schedule (with a starting dose of 20 mg, 50 mg, 100 mg once daily) until they reach the designated target dose (50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg). Once the MTD or RP2D is established for group 1, the phase 1a dose escalation can proceed for group 2. The starting dose level for group 2 will be one dose level below the MTD or RP2D established for group 1.

Who Is Running the Clinical Trial?

Newave Pharmaceutical Inc

Lead Sponsor

Trials

4

Recruited

270+

Citations

1. haematologica.org haematologica.org/article/view/haematol.2023.284353

LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor ... The data presented here indicate that LP-118 increases survival and decreases tumor growth in 2 leukemia xenograft models and can target ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694131/

LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor ... The data presented here indicate that LP-118 increases survival and decreases tumor growth in 2 leukemia xenograft models and can target cells harboring ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04771572

NCT04771572 | Study of Oral Administration of LP-118 in ... ... Efficacy of LP-118 in Subjects With Relapsed or Refractory Hematological Malignancies. Conditions. Non Hodgkin LymphomaRichter TransformationMultiple MyelomaT ...

4. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3640/502513/Pre-Clinical-Evaluation-of-a-New-Generation-Orally

Pre-Clinical Evaluation of a New-Generation Orally ... LP-118 showed encouraging anti-MCL activity as single agent and in combination with standard of care agents in vitro and in vivo, warranting ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121026690

Characterization of LP-118, a Novel Small Molecule ... Collectively, our in vitro studies demonstrated preclinical efficacies of LP-118 in primary CLL samples and Gly101Val mutant cells. LP-118 is ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)03724-3/fulltext

649TiP A phase I/Ib study evaluating the safety, ... The safe starting dose of LP ... To mitigate risk of TLS, an accelerated step-up dosing schedule of LP-118 will be used to reach the target dose for each cohort.

7. ctsearchsupport.org ctsearchsupport.org/clinical-trials/study-of-oral-administration-of-lp-118-in-patients-with-relapsed-or-refractory-nhl-rt-mm-t-pll-acute-leukemia-aml-all-mds-mds-mpn-and-mf

A drug, LP-118, to treat blood cancer that has come back ... To find out:The highest dose of LP-118 that's safe to giveIf LP-118 is safe and works well to treat blood cancer that has relapsed or is refractory.