Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04775745
Other study ID # LP-168-US-I01
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date July 19, 2021
Est. completion date December 31, 2025

Study information

Verified date November 2023
Source Newave Pharmaceutical Inc
Contact Anna Chen, MD, PhD
Phone (206) 335-3820
Email yu@newavepharma.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a phase I, multi-center, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and clinical activity of LP-168 in subjects with relapsed or refractory B-cell malignancies. LP-168 is a small molecule inhibitor.


Description:

The primary objectives for the study are to assess the safety and tolerability profile, determine the maximum tolerated dose (MTD), and/or the recommended Phase 2 dose (RP2D) of LP-168 administered once or twice daily as a single agent dosed orally in adult subjects with relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL); and to characterize the pharmacokinetics (PK) profile of LP-168 in adult subjects with relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL). Secondary objectives of the study are to evaluate preliminary efficacy regarding the effect of LP-168 on progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) in adult subjects with relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL). Once the MTD is declared and the RP2D is established, additional subjects will be enrolled in a cohort expansion phase (Phase 1b).


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date December 31, 2025
Est. primary completion date July 31, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: A subject will be eligible for study participation if he/she meets the following criteria: - Subjects are eligible with B-cell malignancies, WM, FL, MCL, MZL, DLBCL, HCL, CLL, SLL, based upon 2016 updated WHO classification. Those subjects with WM, FL, MCL, DLBCL, or HCL must have received at least 2 prior systemic therapies. - 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). - Subjects must have adequate bone marrow independent of growth factor support per local laboratory reference range at screening as follows: - Absolute Neutrophil Count (ANC) =1000/uL; - An exception is for subjects with an ANC<1000/uL and bone marrow heavily infiltrated with underlying disease (approximately 60% or more) may use growth factor to achieve the ANC eligibility criteria per discussion between the Investigator and the Medical Monitor. - Platelet count = 50,000/µL - OR - Platelet count = 20,000/ µL if thrombocytopenia is clearly due to CLL disease under study (per Investigator discretion) - Hemoglobin =8.0g/dL, and can be achieved by transfusion Exclusion Criteria: A subject will not be eligible for study participation if he/she meets any of the following criteria. - Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug, or has not recovered to = Grade 1 clinically significant adverse effect(s)/toxicity(s) of the previous therapy (other than alopecia): - Any anti-cancer therapy including chemotherapy, biologic or immunotherapy, radiotherapy, etc; - Any investigational therapy, including targeted small molecule agents. - For CLL subjects who come off BCR antagonists (BTK inhibitors, PI3K inhibitors, etc.) treatment, allow washout for 2 days as these subjects progress quickly after treatment discontinuation and then remain eligible (steroids may be given during these two days to allow disease control). - Subjects who require immediate cytoreduction. However, subjects may receive up to two days of steroids for symptoms of impending organ impairment and remain eligible. - 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. - Subjects require treatment with systemic acid-reducing agents including H-2-receptor antagonists and proton pump inhibitors with the following exceptions: - Proton pump inhibitors should be discontinued at least 7 days prior and held throughout the study - If concurrent use of an H2 blocking agent is necessary, it must be administered only between 2 and 3 hours after the dose of LP-168. If not taken during this time, the dose of H2 blocking agents should not be taken again until 2-3 hours after the next dose of LP-168. - If concurrent use of a local antacid is necessary, it must be administered 2 or more hours before and/or 2 or more hours after the dose of LP-168. - Subject has significant screening electrocardiogram (ECG) abnormalities including. 2nd degree AV block type II 3rd degree block, Grade 2 or higher bradycardia, and corrected QT interval (QTc) = 480ms. - Serum amylase > 1.5 × ULN or serum lipase > 1.5 × ULN. - Subject has any history of Richter's transformation for Phase 1a portion of the trial. - Subjects who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 90 days of the first dose of LP-168, or patients on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Patients in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids and/or up to 20 mg/day prednisone or equivalent systemic steroids for ongoing GVHD is permitted. - Subject has a history of other active malignancies other than B-cell malignancies within the past 3 years prior to study entry, with the exception of: - Adequately treated in situ carcinoma of the cervix uteri; - Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; - Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. - Subject requires anticoagulation with Warfarin.

Study Design


Intervention

Drug:
LP-168
For the dose escalation phase, LP-168 will be given once or twice daily at the following dose levels:100 mg QD,150 mg QD, 100 mg BID, 300 mg QD, 150 mg BID, 450 mg QD, 225 mg BID, 600 mg QD, 800 mg QD, and 1000 mg QD.
LP-168
For the dose expansion phase, subjects will receive once or twice daily dose of LP-168 at the Recommended Phase 2 Dose (RP2D). The RP2D may be as high as the MTD and will be determined following evaluation of Phase I Dose Escalation results.

Locations

Country Name City State
United States University of Cincinnati Cincinnati Ohio
United States Ohio State University Columbus Ohio
United States Duke Univerisity Durham North Carolina
United States Huntsman Cancer Institute, University of Utah Salt Lake City Utah

Sponsors (1)

Lead Sponsor Collaborator
Newave Pharmaceutical Inc

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum Tolerated Dose (MTD) When more than 1 DLT occurs in = 6 subjects in a dosing cohort, dose escalation will be stopped and this dose level will be identified as the non-tolerated dose. Doses between the non-tolerated dose and the preceding lower dose, where = 1 DLT occurred, may be explored to more precisely define the MTD. Up to 24 months, each cycle is 28 days
Primary Recommended Phase 2 dose (RP2D) The RP2D may be as high as the MTD or a lower dose and will be selected in discussion with the Investigators and the Sponsor based on longer term safety data, preliminary efficacy data, and PK data. Up to 24 months, each cycle is 28 days
Primary Pharmacokinetic (PK) profile of LP-168 Maximum Plasma Concentration [Cmax] 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)
Primary Pharmacokinetic (PK) profile of LP-168 Area Under the Curve [AUC] 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
Primary Pharmacokinetic (PK) profile of LP-168 Time at Maximum Concentration [Tmax] 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
Secondary Progression-Free Survival (PFS) PFS is measured from the time of first study drug administration until the first date that recurrent or progressive disease is objectively documented. Up to 24 months, each cycle is 28 days
Secondary Objective Response Rate (ORR) ORR is defined as the sum of complete response (CR) and partial remission rates. Up to 24 months, each cycle is 28 days
Secondary Duration of Response (DOR) The duration of overall response is measured from the time measurement criteria are met for CR or PR (which is first recorded) until the first date that recurrent or progressive disease is objectively documented Up to 24 months, each cycle is 28 days
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT01804686 - A Long-term Extension Study of PCI-32765 (Ibrutinib) Phase 3
Recruiting NCT05976763 - Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma Phase 3
Recruiting NCT03676504 - Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR Phase 1/Phase 2
Recruiting NCT05365659 - IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas Phase 1
Recruiting NCT05471843 - Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma Phase 1/Phase 2
Recruiting NCT05076097 - A Study of OLR in First-line Treatment of Mantle Cell Lymphoma Phase 2
Active, not recruiting NCT03891355 - Carfilzomib + Lenalidomide and Dexamethasone for BTK Inhibitors Relapsed-refractory or Intolerant MCL Phase 2
Active, not recruiting NCT04082936 - A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma Phase 1/Phase 2
Recruiting NCT04883437 - Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas Phase 2
Terminated NCT03585725 - A Pilot Investigator-Initiated Study of Ribavirin in Indolent Follicular Lymphoma and Mantle Cell Lymphoma Early Phase 1
Recruiting NCT02892695 - PCAR-119 Bridge Immunotherapy Prior to Stem Cell Transplant in Treating Patients With CD19 Positive Leukemia and Lymphoma Phase 1/Phase 2
Terminated NCT02877082 - Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients Phase 2
Completed NCT01665768 - Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma Phase 2
Completed NCT01437709 - Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell Transplant Phase 2
Completed NCT00963534 - Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma. Phase 1/Phase 2
Completed NCT00921414 - Mantel Cell Lymphoma Efficacy of Rituximab Maintenance Phase 3
Withdrawn NCT00541424 - Combined CT Colonography and PET Imaging in Mantle Cell Lymphoma N/A
Completed NCT01456351 - Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab Phase 3
Completed NCT01851551 - Phase 1/2 Study of VSLI Plus Rituximab in Patients With Relapsed and/or Refractory NHL Phase 1/Phase 2
Completed NCT03295240 - The Study of Bendamustine, Rituximab, Ibrutinib, and Venetoclax in Relapsed, Refractory Mantle Cell Lymphoma Early Phase 1