Study of Oral Administration of LP-168 in Patients With Relapsed or Refractory B-cell Malignancies.

Launched by NEWAVE PHARMACEUTICAL INC · Feb 25, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called LP-168, which is being tested for patients with certain types of blood cancers known as B-cell malignancies, including chronic lymphocytic leukemia (CLL), follicular lymphoma, and diffuse large B-cell lymphoma, among others. The main goals of the study are to find out how safe LP-168 is, how well it works, and how the body processes it. This is a Phase 1 trial, meaning it is one of the first steps in testing a new treatment in people.

To be eligible for this trial, participants should be adults aged 65 or older who have already received at least two previous treatments for their cancer. They also need to have certain blood test results that show their body can handle the trial medication. Participants can expect to take LP-168 orally and will be monitored closely for any side effects or changes in their condition throughout the study. It's important to note that this trial is currently recruiting participants, and those who qualify will play a crucial role in helping researchers understand how this new treatment may benefit patients with these specific blood cancers.

Gender

ALL

Eligibility criteria

• 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.