LP-168 and Obinutuzumab for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Variants of This

NCT06978088 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UCCC-HEM-24-02
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Multicenter Parallel 2 Cohort Phase 2 Study of LP-168 and Obinutuzumab for Previously Treated, and T474 Gatekeeper Mutant Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Variants of This.

Conditions

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Small Lymphocytic Lymphoma; CLL/SLL; Chronic Lymphocytic Leukemia

Keywords

LP-168; Obinutuzumab; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete remission/ Complete remission with incomplete count (CR/CRi) defined by the IWCLL 2018 criteria

  To assess the complete response (CR), complete response with incomplete marrow recovery (CRi) rate of LP-168 + obinutuzumab in each cohort following 12 cycles of treatment.

  12 months

Secondary Outcomes (12)

• Overall response rate- defined by the IWCLL 2018 criteria

  6 months

• Safety and tolerability - CTCAE

  6 years

• Undetectable minimal residual disease (MRD) complete remission (CR) after completion of cycle 12 of therapy defined by negative leukemia cell to the 10-6 using Clonoseq.

  12 months

• Duration of response (DOR), progression free survival (PFS) and overall survival (OS) of patients receiving LP-168 together with obinutuzumab in each cohort of patients.

  6 years

• PK of LP-168 via time to reach maximum plasma concentration

  At the end of cycle 12 or 336 days from the start of LP-168 (each cycle is 28 days)

Other Outcomes (9)

• Signaling measured by immunoblot analysis

  Screening (28 days prior to the first dose of trial treatment), Baseline pre-treatment (before C1D1 dosing), Cycle 1 Day 8, Cycle 6 Day 1, and Cycle 12 Day 1 of therapy in cohort 2. Each cycle is 28 days.

• Chemokines production measurement at specific timepoints

  Screening (28 days prior to the first dose of trial treatment), Baseline pre-treatment (before C1D1 dosing), Cycle 1 Day 8, Cycle 6 Day 1, and Cycle 12 Day 1 of therapy in cohort 2. Each cycle is 28 days.

• Extracellular vesicles (EVs) production measured by the number of vesicles produced in CLL cells

  Baseline pretreatment (before C1D1 dosing), Cycle 1 Day 8, Cycle 1 Day 28, and the end of Cycles 6 and 12 of therapy for cohort 2. Each cycle is 28 days.

Study Arms (2)

Cohort 1

EXPERIMENTAL

Cohort 1: One or more prior therapies for CLL/SLL including BCL2 inhibitor (BCL2i), and/or chemotherapy and/or BTK inhibitor (BTKi). • Note: Patients can be eligible if their CLL/SLL has been non-responsive to a covalent and noncovalent BTKi. Patients intolerant to BTKi whose disease becomes resistant to a second one are eligible to enroll. Prior treatment with CD20 will not be exclusionary.

Drug: LP-168; Drug: Obinutuzumab

Cohort 2

EXPERIMENTAL

Cohort 2: Treatment with a prior BTKi (covalent and noncovalent) and have a BTK gatekeeper mutation in the T474 coordinate. prior treatment with BCL2 or chemotherapy will not exclude patients

Drug: LP-168; Drug: Obinutuzumab

Interventions

LP-168 DRUG

Patients will receive LP-168 200 mg daily beginning day 1 of therapy for 12 cycles.

Cohort 1; Cohort 2

Obinutuzumab DRUG

Patients will with LP-168 and then receive obinutuzumab for a total of 6 cycles, beginning cycle 7, days 1, 2, 8 and 15, and then day 1 of cycles 8-12. A minimum of 12 cycles of therapy will be administered.

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CLL or SLL meeting criteria established in the 2018 iwCLL criteria and requiring treatment. Patients with variation in flow cytometry findings will be allowed to enroll if cytogenetics and/or mutational studies are supportive of CLL/SLL variant.
• a) Note: Variation in flow cytometry is defined as patients who have atypical immunophenotyping for CLL (CD5 negative, CD23 negative or surface expression of CD79b that is bright ) but clinically behave like CLL (leukocytosis, lymphadenopathy and splenomegaly) and have the FISH/Cytogenetics translocations(del 13q, trisomy 12, Del11q) or genomic features (XPO1, NOTCH1, SF3B1, FBXW7, MYD88, BIRC3, TRAF3, NFKBIE, SAMHD1, POT1, HIST1H1E, CHD2, ZMYM3, EGR2 and others) that are suggestive of CLL.
• Cohort 1: One or more prior therapies for CLL/SLL including BCL2 inhibitor (BCL2i), and/or chemotherapy and/or BTK inhibitor (BTKi).
• Cohort 2: Treatment with a prior BTKi (covalent and noncovalent) and have a BTK gatekeeper mutation in the T474 coordinate.
• Age ≥18 years.
• ECOG performance status ≤2 (or Karnofsky ≥60%, see Appendix A).
• Patients must have adequate organ and marrow function as defined below:
• ANC ≥1,000/mcL, unless if neutropenia is due to underlying CLL bone marrow disease.
• Platelets ≥ 50,000/ µL unless if thrombocytopenia is due to underlying CLL bone marrow disease then platelets of ≥20,000 is acceptable
• Total bilirubin ≤1.5 x ULN (excepting Gilbert's syndrome, who may have a bilirubin \> 1.5 × ULN, per discussion between the Investigator and the UC PI).
• AST and ALT ≤2.5 × ULN.
• Estimated glomerular filtration rate (by Modification of Diet in Renal Disease \[MDRD\]) or Chronic Kidney Disease Epidemiology \[CKD-EPI\]) ≥ 30 mL/min
• Women of childbearing potential and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s) throughout the study and for 30 days after discontinuing study drug:
• Total abstinence from sexual intercourse as the preferred lifestyle of the patient; periodic abstinence is not acceptable.
• Surgically sterile partner(s) by vasectomy, bilateral orchiectomy, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.

You may not qualify if:

• Patients with active Richter's transformation.
• Patient 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 patients who come off BCR antagonist treatment (BTK inhibitors, PI3K inhibitors, etc.), allow washout for 5 half-lives as these patients progress quickly after treatment discontinuation and then remain eligible (steroids may be given during the washout to allow for disease control, see d below for details).
• When a patient's intercurrent health condition would require short term steroid use this should be discussed with the Investigator in consultation with the Medical Monitor. Steroids are allowed for disease control in those R/R patients when use is limited to 2-3 days to allow for control of the underlying disease. Steroids may be given during the washout to allow for disease control.
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous, in the opinion of the Investigator.
• Patients who require anti-coagulation with warfarin or equivalent Vitamin K antagonist.
• Major surgery within 14 days prior to the first dose of study drug.
• Patients who have received the following medications or therapies within 5 half-lives or 14 days, whichever is shorter, prior to the first dose of study drug:
• Cytochrome P450, family 3, subfamily A (CYP3A4) strong inhibitors and strong CYP2C8 inducers/inhibitors (see the list in Appendix B)
• Strong CYP3A4 inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort (Appendix B)
• There is a 28-day washout period required for patients who have had prior CAR T treatment if there is no evidence of cytokine release syndrome (CRS) or other AEs related to the CAR T treatment per discussion with the UC PI; reduced washout period may be acceptable after discussion with UC PI.
• Drugs that are substrates of MATE1 and MATE2-K should be avoided or substituted for other medications if possible. Use of these (if done) must be discussed with the PI of the study. (Appendix D).
• Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or Star fruit within 3 days prior to the first dose of study drug.

Sponsors & Collaborators

• Zulfa Omer: lead
• Newave Pharmaceutical Inc: collaborator

Study Sites (1)

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

UCCC Clinical Trials Office

CONTACT

513-584-7698; cancer@uchealth.com

Zulf Omer, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Multicenter Parallel 2 Cohort

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: May 18, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2034
• Last Updated: August 14, 2025

Record last verified: 2025-07

Locations

US (1)