A Phase I Study of LP-118 In Combination With Ponatinib, Dexamethasone And Blinatumomab For Adults With Newly-Diagnosed, BCR::ABL1-Positive ALL

A Phase I Study of the Bcl-2/Bcl-XL Inhibitor LP-118 In Combination With Ponatinib, Dexamethasone And Blinatumomab For Adults With Newly-Diagnosed, Philadelphia-Chromosome/BCR::ABL1-Positive Acute Lymphoblastic Leukemia

The purpose of this research study is to see if a drug called LP-118 is safe and effective for treating adults with Philadelphia chromosome-positive (Ph+) B cell acute lymphoblastic leukemia (ALL), when given with ponatinib, dexamethasone, methotrexate and blinatumomab (the standard treatment for this type of cancer).

Study Overview

• Status: Not yet recruiting
• Conditions: Philadelphia Positive Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: LP-118

Detailed Description

Philadelphia-Chromosome/BCR::ABL1-Positive (Ph+) acute lymphoblastic leukemia (ALL) is a type of blood cancer that happens when a specific genetic change occurs in the DNA of certain blood cells, leading to uncontrolled growth of cells. Ph+ ALL is a more aggressive form of leukemia compared to other types but with specific medications called tyrosine kinase inhibitors, treatment outcomes have significantly improved. Unfortunately, some patients still do experience relapsed disease, when their leukemia comes back after treatment, which is challenging to treat. Therefore, research is ongoing to determine ways to improve therapy and outcomes for patients with Ph+ ALL.

The purpose of this study is to learn more about LP-118 and its side effects and decide on acceptable doses when combined with FDA approved therapy for adult patients with Ph+ ALL. All participants will receive standard of care treatment for newly diagnosed Ph+ ALL consisting of the FDA approved drugs ponatinib, dexamethasone, intrathecal (injection into the spinal canal, also called "spinal tap") and systemic methotrexate and blinatumomab. This study will investigate different dose levels of LP-118 when given with his treatment combination to determine the most effective doses that can be safely given to patients with Ph+ ALL. This means that enrolled patients will receive progressive increasing or decreasing doses of LP-118 until the highest effective and safe dose is determined, while closely monitoring patients for any side effects or reactions. The highest dose is the dose that is the most effective dose that can be safely given to patients. This study will also preliminarily investigate if the addition of LP-118 improves treatment responses and outcomes for patients. If this trial is successful, the effectiveness of LP-118 added to this treatment regimen to treat Ph+ ALL will be studied in the next phase of clinical trials.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dianna Auman, RN; Phone Number: 336-716-1122; Email: Dianna.Roesler@Advocatehealth.org

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health Levine Cancer
      • Contact: Katarzyna Wydrzynska-Gruner, RN; Phone Number: 704-355-2000; Email: katarzyna.wydrzynskagruner@advocatehealth.org
      • Sub-Investigator: Thomas Knight, MD
    • Winston-Salem, North Carolina, United States, 27157
      • Atrium Health Wake Forest Baptist Comprehensive Cancer Center
      • Principal Investigator: Madelyn Burkart, MD
      • Contact: Dianna Auman, RN; Phone Number: 336-716-1122; Email: Dianna.Roesler@Advocatehealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to understand and willingness to sign an IRB-approved informed consent.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status (PS) ≤ 2.
• Histological or cytological confirmation of newly diagnosed CD19-positive Philadelphia-chromosome/BCR::ABL1-positive ALL.
• Creatinine clearance: ≥60 mL/min, determined by the Cockroft-Gault formula, or measured by a 24-hour urine collection.
• Bilirubin ≤ 1.5 × upper limit of normal (ULN) - Unless liver abnormalities considered due to Gilbert's syndrome or of non-hepatic origin i.e., leukemic involvement. For patients with Gilbert's syndrome, bilirubin ≤1.5 x of their baseline bilirubin level will be required.
• Aspartate aminotransferase (AST) - Unless liver abnormalities considered due to Gilbert's syndrome or of non-hepatic origin i.e., leukemic involvement. For patients with Gilbert's syndrome, bilirubin ≤1.5 x of their baseline bilirubin level will be required.
• Alanine aminotransferase (ALT) - Unless liver abnormalities considered due to Gilbert's syndrome or of non-hepatic origin i.e., leukemic involvement. For patients with Gilbert's syndrome, bilirubin ≤1.5 x of their baseline bilirubin level will be required.
• Individuals of childbearing potential (ICBP) must have a negative serum pregnancy test. NOTE: Individuals who may become pregnant are considered to have childbearing potential unless they are surgically infertile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).
• ICBP must be willing to use two forms of contraception, one of which must be a barrier method and the other must be a highly effective contraceptive method from the time of informed consent until 6 months after study treatment discontinuation. Male participants with female partners of reproductive potential will need to agree to use contraception methods described above during study treatment and for at least 6 months after completion of all study treatment.
• Male participants must agree to refrain from sperm donation during study treatment and for at least 6 months after completion of all study treatment.
• Ability to ingest oral medications without a malabsorption condition, known dysphagia, short-gut syndrome, gastroparesis, or other conditions that may limit the ingestion or gastrointestinal absorption, distribution, metabolism and excretion of drugs administered orally, per the enrolling investigator.

Exclusion Criteria:

• Any prior treatment for ALL except for a single dose of intrathecal (IT) chemotherapy, corticosteroids, hydroxyurea, a single dose of vincristine, cytarabine, leukapheresis, and/or a BCR::ABL1-targeted tyrosine kinase inhibitor. Permitted prior treatment is limited to a duration of no longer than 14 days. Permitted prior treatment must be stopped at least 24 hours prior to starting study therapy.
• Women who are pregnant, nursing, or who plan to become pregnant while in the study and for at least 6 months after the last administration of all study treatment. NOTE: breast milk cannot be stored for future use while the mother is being treated on study. Pregnant participants are excluded from this study because ponatinib, blinatumomab, and methotrexate have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ponatinib, blinatumomab, and methotrexate breastfeeding should be discontinued if the patient is treated with ponatinib, blinatumomab, and methotrexate.
• Active second malignancy except for localized prostate cancer, basal cell or squamous cell carcinoma of the skin and carcinoma in situ of the skin or cervix.
• Unstable or severe uncontrolled medical condition in the opinion of the enrolling investigator (e.g., unstable cardiac function or unstable pulmonary condition; uncontrolled infection).
• Participants with known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV) are eligible if no evidence of active viral replication by blood testing (i.e. negative viral loads). HIV positive participants must be on active anti-retroviral therapy and willing to continue therapy during study treatment.
• Uncontrolled cardiac disease as determined by the enrolling investigator.
• Major surgery, as determined by the enrolling investigator, within 2 weeks before enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination of LP-118, ponatinib, dexamethasone, blinatumomab and methotrexate; LP-118 will be given as tablets of 10mg or 100mg during the induction II course only in combination with ponatinib, dexamethasone, methotrexate and blinatumomab. . Ponatinib, dexamethasone and methotrexate dosing will remain fixed, whereas LP-118 dosing will be dependent on the dose level to which a participant is assigned.

Drug: LP-118; s LP-118 dosing will be dependent on the dose level to which a participant is assigned: 50mg PO; 100mg PO; 200mg PO; 300mg PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimation of the Maximum Tolerated Dose (MTD) for LP-118 (Dose Escalation)	Binary variable indicating if a Dose Limiting Toxicity (DLT) occurred.	The DLT monitoring period is from Day 1 of Course 2 until the end of Course 2 (approximately 21 days).
Identification of the Recommended Phase 2 Dose (RP2D) LP-118 (Dose Expansion)	Binary variable indicating if a Dose Limiting Toxicity (DLT) occurred.	The DLT monitoring period is from Day 1 of Course 2 until the end of Course 2 (approximately 21 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS).	The time from treatment administration to death from any cause, or until last contact if the patient has not died	At most 10 years.
Relapsed-Free Survival (RFS).	Time from Complete Response (CR) or Complete Response with Incomplete Hematologic Recovery (CRi) to disease relapse or death (whichever occurs first) or otherwise censored at the date of the last disease assessment.	At most 10 years.
Event-Free Survival (EFS).	Time from start of therapy until failure to achieve CR/CRi, relapse, or death from any cause or otherwise censored at the date of the last disease assessment.	At most 10 years.
Overall Complete Molecular Response (CMR) rate.	Binary variable indicating if a CMR at any time while on study.	At most 10 years.
Measurable Residual Disease (MRD) rate.	Binary variable indicating if MRD was achieved.	Approximately 3 years.
Isolated CNS relapse rate.	Binary variable indicating if isolated CNS relapse occurred.	At most 10 years.
Complete Response (CR) rate.	Complete clinical remission defined as the disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blasts or extramedullary disease, with recovery of hematopoiesis defined by ANC ≥1000/μL and platelets ≥100,000/μL.	Approximately 3 years.
Complete clinical remission with incomplete count recovery (CRi)	Complete clinical remission with incomplete count recovery (CRi) defined as complete clinical remission except with ANC< 1000/μL and/or platelets <100,000/μL	Approximately 3 years.
Overall Response (OR) rate.	A binary variable indicating if a CR or CRi was achieved.	Approximately 3 years.
Safety (toxicity occurrence)	Binary variables indicating the occurrence of toxicities per CTC V5.0.	Approximately 3 years.

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI); Newave Pharmaceutical Inc; Atrium Health Wake Forest Baptist
• Investigators: Principal Investigator: Madelyn Burkart, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: cancer; Leukemia; Philadelphia-Chromosome positive
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Hemic and Lymphatic Diseases; Neoplasms; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: IRB00127277; P30CA012197 (U.S. NIH Grant/Contract); ONC-LEUK-2405 (Other Identifier: Atrium Health Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No