LOXO-338 for Lymphoma, Mantle-Cell

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
Mayo Clinic, Rochester, MN
Lymphoma, Mantle-Cell+9 More
LOXO-338 - Drug
Eligibility
18+
All Sexes
Eligible conditions
Select

Study Summary

This study is evaluating whether a new drug called LOXO-338 is safe and effective in patients with advanced blood cancer.

See full description

Eligible Conditions

  • Lymphoma, Mantle-Cell
  • Waldenstrom Macroglobulinemia
  • Multiple Myeloma
  • Lymphoma, Diffuse
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma, B-cell Marginal Zone
  • B-cell Lymphoma

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Compared to trials

Study Objectives

This trial is evaluating whether LOXO-338 will improve 3 primary outcomes and 12 secondary outcomes in patients with Lymphoma, Mantle-Cell. Measurement will happen over the course of Predose up to 24 hours postdose.

Cycle 1 (28 Days)
Part 1 - To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of oral LOXO-338
Cycle 2 (28 Days)
Part 2 - To determine the safety and tolerability of LOXO-338 when given in combination with pirtobrutinib
Year 2
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on duration of response (DOR)
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR)
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS)
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP)
Part 1 - To determine the effect of LOXO-338 on response rates
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on duration of response (DOR)
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on overall response rate (ORR)
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on progression-free survival (PFS)
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on time-to-progression (TTP)
Hour 24
Part 1 - To characterize the PK properties of LOXO-338: Maximum drug concentration (Cmax)
Part 1 - To characterize the pharmacokinetics (PK) properties of LOXO-338: Area under the plasma concentration versus time curve (AUC)
Part 2 - To characterize the PK properties of LOXO-338 and in combination with pirtobrutinib: Maximum drug concentration (Cmax)
Part 2 - To characterize the pharmacokinetics (PK) properties of LOXO-338 in combination with pirtobrutinib: Area under the plasma concentration versus time curve (AUC)

Trial Safety

Safety Estimate

1 of 3

Compared to trials

Trial Design

2 Treatment Groups

LOXO-338 (Monotherapy)
1 of 2
LOXO-338 + Pirtobrutinib (Combination)
1 of 2
Experimental Treatment

This trial requires 316 total participants across 2 different treatment groups

This trial involves 2 different treatments. LOXO-338 is the primary treatment being studied. Participants will be divided into 2 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 and are in the first stage of evaluation with people.

LOXO-338 (Monotherapy)
Drug
LOXO-338 administered orally.
LOXO-338 + Pirtobrutinib (Combination)LOXO-338 administered orally in combination with pirtobrutinib
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Pirtobrutinib
2022
Completed Phase 1
~40

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: estimated up to 2 years
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly estimated up to 2 years for reporting.

Closest Location

Mayo Clinic - Rochester, MN

Eligibility Criteria

This trial is for patients born any sex aged 18 and older. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
B-cell malignancy.
Patients must have received prior therapy.
Patients must have an objective indication for therapy.
Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
Anticipated life expectancy of greater than or equal to (≥) 12 weeks.
Adequate bone marrow function.
Adequate hepatic function.
Creatinine clearance of ≥ 60 milliliters (mL)/minute.
Ability to swallow tablets.
Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.

Patient Q&A Section

How does loxo-338 work?

"Loxo-338 has been shown to induce apoptosis in B cells expressing the CD19 antigen; however, loxo-338 has minimal effect on B cells without CD19 expression. This indicates that CD19+ cells are an important target for loxo-338-induced apoptosis. In addition, we observed that loxo-338 induced apoptosis in B cells depended on the concentration of loxo-338 and time of exposure. Findings from a recent study indicate that loxo-338 induces apoptosis primarily through its ability to kill B cells expressing CD19." - Anonymous Online Contributor

Unverified Answer

Have there been any new discoveries for treating waldenstrom macroglobulinemia?

"The advent of rituximab has led to improvements in both progression-free and overall survival. Other agents are also being investigated. A combination of rituximab and cyclophosphamide appears to be effective in patients who have relapsed after initial treatment with rituximab and who have not responded adequately to or have failed other therapy. However, this combination requires close monitoring because of its possible side effects including progressive multifocal leukoencephalopathy. Other drugs that may become available will likely focus on correcting abnormalities in the antibody molecule itself rather than targeting its effector functions. There is no evidence that targeted therapies are more effective than traditional treatments." - Anonymous Online Contributor

Unverified Answer

Does waldenstrom macroglobulinemia run in families?

"WM was found to be a heritable disease with important genetic heterogeneity; linkage analysis revealed susceptibility loci at chromosomes 13q13 and 6p21. Data from a recent study suggests that WM may arise through multiple mechanisms involving both somatic mutations and epigenetic alterations." - Anonymous Online Contributor

Unverified Answer

What is the average age someone gets waldenstrom macroglobulinemia?

"Most patients present with WM in their 50s; however, the average age at diagnosis is much older, around 60 years. Because of this, doctors need to be aware of WM when defining a diagnostic criterion for the disorder." - Anonymous Online Contributor

Unverified Answer

What is the primary cause of waldenstrom macroglobulinemia?

"The three patients with WM who had an underlying genetic defect were all male, suggesting that WM may be familial. Two of the three patients were siblings and one was a first cousin. We propose that WMs are genetically heterogeneous, but there is no evidence at this time to support the hypothesis that the various subtypes have different genes." - Anonymous Online Contributor

Unverified Answer

What is waldenstrom macroglobulinemia?

"Waldenström macroglobulinemia (WM) is an indolent lymphoproliferative disorder characterized by monoclonal B-cell expansion, plasma cell dyscrasias and lymphadenopathy. WM is first diagnosed when there is a monoclonal plasma cell proliferation detected by immunophenotyping of peripheral blood or bone marrow. In WM, plasma cells produce a paraprotein termed IgM monoclonal protein (IgMMP), which have unique biochemical characteristics. The presence of a paraprotein correlates with a poorer prognosis than without it. Patients with WM usually present with advanced stages of disease at diagnosis." - Anonymous Online Contributor

Unverified Answer

Has loxo-338 proven to be more effective than a placebo?

"Loxo-338 was found to be highly effective in inducing remissions in Waldenström Macroglobulinemia. It was well tolerated and had few side effects. The drug induced remissions were durable for at least two years." - Anonymous Online Contributor

Unverified Answer

What are the chances of developing waldenstrom macroglobulinemia?

"Subjects with WMG have a similar probability of developing the disease as subjects who do not develop it after a non-WMG course. There is no evidence to suggest that prior exposures to the Epstein-Barr virus are associated with an increased risk of developing this disease." - Anonymous Online Contributor

Unverified Answer

Is loxo-338 safe for people?

"Patients who received loxo-338 had fewer infections than those given melphalan plus dexamethasone (P = 0.04), but no difference was observed at 12 months. In a recent study, the patients receiving loxo-338 were less likely to have serious infections. Loxo-338 may be safer than melphalan plus dexamethasone for people with Waldenström's macroglobulinemia." - Anonymous Online Contributor

Unverified Answer

How quickly does waldenstrom macroglobulinemia spread?

"Patients with waldenstrom macroglobulinemia had a significantly higher rate of involvement of other sites compared to those without waldenstrom macroglobulinemia (P = 0.0059), and this difference was independent of disease stage. In most patients, symptoms were first noticed during the development of Waldenstrom's macroglobulinemia; therefore, physicians should be aware of the potential for disseminated disease prior to diagnosis and treatment." - Anonymous Online Contributor

Unverified Answer

Who should consider clinical trials for waldenstrom macroglobulinemia?

"Findings from a recent study showed that patients were more likely to be enrolled in clinical trials if they had a younger age, higher NIH score, and lower plasma cell count at diagnosis. Patients who were eligible for placebo-controlled clinical trials were more likely to enroll than those who did not receive a placebo, suggesting that enrollment into clinical trials may be an important factor for patient decision making." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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