What side effects are associated with this type of intervention?

Common treatments for Waldenstrom Macroglobulinemia include proteasome inhibitors (like bortezomib), immunomodulatory drugs (like lenalidomide), and monoclonal antibodies (like rituximab). Known side effects of these treatments can include peripheral neuropathy, myelosuppression, fatigue, gastrointestinal issues, and increased risk of infections. For small molecule inhibitors similar to LP-168, side effects often include cytopenias, fatigue, gastrointestinal disturbances, and potential cardiac and renal toxicities. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Waldenstrom Macroglobulinemia, including small molecule inhibitors. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was the first small molecule inhibitor approved for this condition. Other treatments include proteasome inhibitors like bortezomib and immunomodulatory drugs such as lenalidomide. These therapies target specific pathways involved in the growth and survival of malignant cells, similar to the mechanism of action being studied for LP-168.

What other types of research exist?

Promising novel alternatives to LP-168 for Waldenstrom Macroglobulinemia patients include ibrutinib and acalabrutinib, both of which are Bruton tyrosine kinase (BTK) inhibitors. These drugs have shown efficacy in B-cell malignancies and are well-studied in clinical trials. Additionally, venetoclax, a BCL-2 inhibitor, is another potential option due to its activity in B-cell lymphomas.

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Small Molecule Inhibitor

LP-168 for Lymphoma

Phase 1

Recruiting

Research Sponsored by Newave Pharmaceutical Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Low-grade B-cell lymphomas as follicular Grade 1, 2, or 3A, marginal zone or small lymphocytic lymphoma.

Subject must have adequate coagulation, renal, and hepatic function, per local laboratory reference ranges at Screening as follows: Activated partial thromboplastin time (APTT) and prothrombin time (PT) not to exceed 1.5 × ULN, Calculated creatinine clearance (CrCl) ≥ 60 mL/min using 24-hour CrCl OR Cockcroft-Gault formula, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 ×ULN; Bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome, who may have a bilirubin > 1.5 × ULN, per discussion between the Investigator and the Medical Monitor).

Must not have

Subject has any history of Richter's transformation for Phase 1a portion of the trial.

Subject has received the following medications or therapies within 7 days prior to the first dose of study drug: Steroid therapy (at dosages equivalent to prednisone >20 mg/day) for anti-neoplastic intent (except as noted in exclusion criteria #3); Cytochrome P450, family 3, subfamily A (CYP3A4) strong inhibitors and strong CYP2C8 inducers/inhibitors. Potent CYP3A4 inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at cycle 1: day 1, day 2, day 8, day 9, day 15, day 22, day 28; at cycle 3: day 28; at cycle 6 day 28; (each cycle is 28 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new oral medication called LP-168 in adults with certain blood cancers that have returned or are resistant to other treatments. LP-168 works by blocking proteins that help cancer cells grow.

Who is the study for?

This trial is for adults with certain B-cell malignancies who've had at least two prior treatments. They should have good kidney, liver, and bone marrow function and not be on strong immune system suppressants or certain other drugs. People with recent cancer therapies, significant heart ECG abnormalities, or a history of Richter's transformation can't join.

What is being tested?

The study tests LP-168, an oral drug for relapsed/refractory B-cell malignancies. It's a phase I trial to see how safe it is and how the body handles it (pharmacokinetics) at different doses.

What are the potential side effects?

Potential side effects of LP-168 aren't detailed here but may include typical reactions to cancer medications such as nausea, fatigue, blood count changes, and possible organ-specific inflammation based on its pharmacological class.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lymphoma is a low-grade B-cell type, such as follicular or marginal zone.

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

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I have a specific type of blood cancer and have had at least 2 treatments if it's WM, FL, MCL, DLBCL, or HCL.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My condition has transformed into a more aggressive form known as Richter's transformation.

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I haven't taken high-dose steroids, certain enzyme inhibitors, or strong medication inducers in the last week.

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I need to take Warfarin for blood thinning.

Select...

I haven't had cancer treatment or experimental drugs in the last 14 days or am not fully recovered from their side effects.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at cycle 1: day 1, day 2, day 8, day 9, day 15, day 22, day 28; at cycle 3: day 28; at cycle 6 day 28; (each cycle is 28 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at cycle 1: day 1, day 2, day 8, day 9, day 15, day 22, day 28; at cycle 3: day 28; at cycle 6 day 28; (each cycle is 28 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and at cycle 1: day 1, day 2, day 8, day 9, day 15, day 22, day 28; at cycle 3: day 28; at cycle 6 day 28; (each cycle is 28 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD)

Pyruvate Kinase

Recommended Phase 2 dose (RP2D)

Secondary study objectives

Duration of Response (DOR)

Objective Response Rate (ORR)

Progression-Free Survival (PFS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dose Expansion PhaseExperimental Treatment1 Intervention

Additional subjects will be recruited to further explore the safety, tolerability, PK, and efficacy in specific subject subgroups.

Group II: Dose Escalation PhaseExperimental Treatment1 Intervention

Three to six subjects per treatment cohort will be assigned to receive sequentially higher oral doses of LP-168 on a once or twice daily schedule for 28 days, starting at a dose of 100 mg/day.

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Waldenstrom Macroglobulinemia (WM) is commonly treated with therapies that target specific pathways involved in the growth and survival of malignant B-cells. Small molecule inhibitors, such as Bruton’s tyrosine kinase (BTK) inhibitors (e.g., ibrutinib), block signals that promote B-cell proliferation and survival. This is crucial for WM patients as it directly interferes with the disease's progression. Other treatments include proteasome inhibitors (e.g., bortezomib), which disrupt protein degradation in cancer cells, leading to cell death, and monoclonal antibodies (e.g., rituximab), which target specific proteins on the surface of B-cells, marking them for destruction by the immune system. These mechanisms are vital as they offer targeted approaches to manage and potentially reduce the burden of WM.