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Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 2NCT06978088

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

A Phase 2 study testing LP-168 and Obinutuzumab in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Small Lymphocytic Lymphoma, run by Zulfa Omer at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LP-168 and Obinutuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
1 Jun 2025to 1 Jun 2034
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • Meet the criteria for inclusion into at least one of the following 2 cohorts:
  • 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.
  • Cohort 2: Treatment with a prior BTKi (covalent and noncovalent) and have a BTK gatekeeper mutation in the T474 coordinate.
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  • 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.
  • Intrauterine device.
  • Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 1-month prior to study drug administration.
  • Women of childbearing potential must have a negative pregnancy result as follows: At Screening on a serum sample obtained within 7 days prior to the first study drug administration. If a urine pregnancy test at any timepoint during the study is positive or indeterminate, a serum pregnancy test will be performed for confirmation.
  • Non-sterile males must refrain from sperm donation, from initial study drug administration until 30 days after the last dose of study drug.
  • Able to provide informed consent.

Who cannot join

  • 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.
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  • 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:
  • Steroid therapy (at dosages equivalent to prednisone >20 mg/day) for anti- neoplastic intent (except as noted in exclusion criterion #2).
  • 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.
  • Patient requires treatment with systemic acid-reducing agents, H2 blocking agent and proton pump inhibitors, with the following exceptions:
  • Proton pump inhibitors should be discontinued at least 7 days or at least 5-half-lives (whichever is shorter) 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.
  • Patient has clinically significant screening electrocardiogram (ECG) abnormalities including:
  • 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, and corrected QT interval (QTcF) ≥ 480ms (calculated per Fridericia's formula [QTcF = QT/RR (1/3)]).
  • For patients with presence of right bundle branch block (RBBB) or left bundle branch block (LBBB), cardiology review is needed to correct QTcF calculation using Sponsor recommended formula (Simplified Formula for Bundle Branch Block). See Appendix C.
  • Other clinically significant ECG abnormalities per PI discretion.
  • Patient has significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 180 days prior to the first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or left ventricular ejection fraction ≤ 40%.
  • Patient has a history of stroke or intracranial hemorrhage within 180 days prior to the first dose of study drug.
  • Patients who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 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.
  • Pregnant women, those planning to become pregnant during the study, and/or breastfeeding women are ineligible for participation.
  • Patients with known malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Known hypersensitivity to any of the components of LP-168 (see Investigators Brochure for a list of components).
  • Patients with active bleeding disorder.
  • NOTE: Von Willebrand's disease or hemophilia will not be excluded if patient is on treatment and well controlled.
  • Patient exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
  • Uncontrolled active systemic infection (bacterial, fungal, viral);
  • Known poorly controlled (defined as less than 200 CD4 count) human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HBsAg positive, or HBcAb positive with detectable HBV DNA load; active hepatitis C defined as HCV antibody positive with HCV RNA positive)
  • Unexplained fever > 38.3°C within 7 days prior to the first dose of study drug administration (if the fever is considered attributed to the patient's malignancy or an explained infection, the Patient may be enrolled at the discretion of the Investigator).
  • Patient has a history of other active malignancies within the past 1 year prior to study entry, with the exception of:
  • Breast cancer or prostate cancer on endocrine therapy with stable disease.
  • Continuation of maintenance therapy in patients with adequately treated malignancy.
  • Cancer with expected survival of 2 years or more or that will not confound evaluation of LP-168 treatment.
  • 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.
  • Patients with active CNS involvement can be enrolled per Investigator discretion; patients with significant clinical symptoms, including any that require treatment with high dose steroid, will be excluded.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

UCCC Clinical Trials Office contact

513-584-7698

cancer@uchealth.com

Zulf Omer, MD contact

United States1 site, 1 recruiting

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

    UCCC CTO, 513-584-7698, cancer@uchealth.com

    Christine Vollmer, mccordce@ucmail.uc.edu

    Recruiting

Other trials in United States

About this study

Official title: A 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

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.

Read the detailed description

This is a multicenter parallel two cohort, phase II clinical trial designed to evaluate the combination of obinutuzumab + LP-168 for the treatment of: 1) previously treated, and 2) BTK T474I ( gate keeper mutation) mutated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) patients. The goal is to establish a safe dosing regimen for the combination and to acquire pilot data characterizing the effectiveness of the combination in increasing the depth of response as reflected in the rate of undetectable Minimal Residual Disease (MRD), complete response (CR). If successful, this would support a larger phase II/III study. A gatekeeper cohort of patients is added to further expand understanding of efficacy and translational biology of LP-168 in this patient population that represents a rapidly emerging unmet medical need in CLL.

Patients will receive LP-168 200 mg daily beginning day 1 of therapy for 12 cycles. Within 2 weeks of completing cycle 6, patients will undergo response evaluation that will include labs, CT scan, and bone marrow biopsy. Patients will then continue 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. At end of Cycle 12 of therapy, patients will be assessed for treatment response and MRD status by labs, CT scans (if clinically indicated), peripheral blood and bone marrow morphology and using NGS Clonoseq (Adaptive Biotechnologies) for MRD status.

Patients with undetectable minimal residual disease (uMRD) CR at this time will have the option to discontinue therapy. Patients with less than CR or detectable MRD (dMRD) will continue therapy with LP-168 with follow up every 6 months. Patient and investigator may choose to repeat MRD testing from the bone marrow later during the disease course and stop therapy if uMRD is achieved. Patients with disease progression (PD) but who are gaining benefit from the drug can continue therapy per PI discretion.

Being tested
LP-168, Obinutuzumab
Keywords
LP-168, Obinutuzumab, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LP-168Drug

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

  • ObinutuzumabDrug

    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.

Study groups in NCT06978088
Study groupRoleWhat they receive
Cohort 1ExperimentalCohort 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.
Receives: Drug: LP-168; Drug: Obinutuzumab
Cohort 2ExperimentalCohort 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
Receives: Drug: LP-168; Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 months

Secondary outcomes (12)

  1. Overall response rate- defined by the IWCLL 2018 criteria

    To assess the overall response rate to LP-168 (CR, CRi, PR, PR-L and nPR) in each cohort of CLL/SLL following 6 cycles of treatment.

    Each patient will be assigned one of the following categories: 1) complete response, 2) partial response/Partial response with lymphocytosis or nodular partial response, 3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) early death from toxicity, 7) early death because of other cause, or 9) unknown (not assessable, insufficient data). Note: By arbitrary convention, category 9 usually designates the "unknown" status of any type of data in a clinical database.

    Measured: 6 months

  2. Safety and tolerability - CTCAE

    To assess the safety and tolerability of LP-168 given with obinutuzumab.

    We will monitor further for SAEs (CTCAE grade >=3) continuously on trial by cohort. The exception is the first 6 patients enrolled (irrespective of cohort) will be evaluated as well for safety of the combination with respect to DLTs as defined by this protocol. Patients will be monitored for regular safety outside the combination using the toxicity monitoring Table 8, given we already have data confirming the safety of the single agent LP-168.

    Measured: 6 years

  3. 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.

    To assess the rate of undetectable measurable residual disease (uMRD), defined by negative leukemia cell to the 10-6 using NGS technique (Clonoseq).

    Measured: 12 months

  4. 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.

    DOR defined as the time from receiving first treatment to disease progression or death for patients who achieve complete or partial response, PFS defined as the interval between the first treatment day to the first sign of disease progression or death from any cause, and OS, defined as time from starting treatment until death, all measured at completion of LP-168 with obinutuzumab treatment.

    Measured: 6 years

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

    To characterize the pharmacokinetics (PK) of LP-168 following administration in participants via time to reach maximum plasma concentration

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

  6. PK of LP-168 via area under the concentration-time curve (AUC)

    To characterize the pharmacokinetics (PK) of LP-168 following administration in participants via area under the concentration-time curve (AUC)

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

  7. Pharmacokinetics (PK) of LP-168 via half-life

    To characterize the pharmacokinetics (PK) of LP-168 following administration in participants via half-life

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

  8. Pharmacokinetics (PK) of LP-168 via clearance rate

    To characterize the pharmacokinetics (PK) of LP-168 following administration in participants via clearance rate

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

  9. Pharmacokinetics (PK) of LP-168 fvia volume of distribution based on plasma concentration measurements

    To characterize the pharmacokinetics (PK) of LP-168 following administration in participants via volume of distribution based on plasma concentration measurements

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

  10. BTK occupancy expressed as the percentage of total BTK that is occupied by the drug LP-168 at the end of pretreatment

    BTK occupancy will be measured in peripheral blood mononuclear cells (PBMCs) and will be expressed as the percentage of total BTK that is occupied by the drug LP-168 at the end of pretreatment (0 days from the start of LP-168).

    Measured: 0 days from the start of LP-168

  11. BTK occupancy expressed as the percentage of total BTK that is occupied by the drug LP-168 at the end of cycle 6 .

    BTK occupancy will be measured in peripheral blood mononuclear cells (PBMCs) and will be expressed as the percentage of total BTK that is occupied by the drug LP-168 at the end of cycle 6 (168 days from the start of LP-168).

    Measured: 168 days from the start of LP-168

  12. BTK occupancy expressed as the percentage of total BTK that is occupied by the drug LP-168 at the end of cycle 12

    BTK occupancy will be measured in peripheral blood mononuclear cells (PBMCs) and will be expressed as the percentage of total BTK that is occupied by the drug LP-168 at the end of cycle 12(336 days from the start of LP-168)

    Measured: 336 days from the start of LP-168

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2025
  2. Study start1 Jun 2025
  3. Primary completion1 Jun 2029 (estimated)
  4. Study completion1 Jun 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Multicenter Parallel 2 Cohort
Masking
None (open label)
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06978088
Sponsor's protocol ID
UCCC-HEM-24-02
Status last verified
Jul 2025
First submitted
9 Apr 2025
Last updated
14 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LP-168 and Obinutuzumab in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Small Lymphocytic Lymphoma, run by Zulfa Omer at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact UCCC Clinical Trials Office (513-584-7698, cancer@uchealth.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete remission/ Complete remission with incomplete count (CR/CRi) defined by the IWCLL 2018 criteria (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06978088.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2025.

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