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).
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 Food and Drug Administration (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
Allocation
NA
Purpose
TREATMENT
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
Atrium Health Levine Cancer
Charlotte, North Carolina, United States
Atrium Health Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Estimation of the Maximum Tolerated Dose (MTD) for LP-118 (Dose Escalation)
Binary variable indicating if a Dose Limiting Toxicity (DLT) occurred.
Time frame: 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.
Time frame: The DLT monitoring period is from Day 1 of Course 2 until the end of Course 2 (approximately 21 days).
Overall Survival (OS).
The time from treatment administration to death from any cause, or until last contact if the patient has not died
Time frame: At most 10 years.
Relapsed-Free Survival (RFS).
Time from Complete Remission (CR) or Complete Remission with Incomplete Hematologic Recovery (CRi) to disease relapse or death (whichever occurs first) or otherwise censored at the date of the last disease assessment.
Time frame: 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.
Time frame: At most 10 years.
Overall Complete Molecular Response (CMR) rate.
Binary variable indicating if a CMR at any time while on study.
Time frame: At most 10 years.
Measurable Residual Disease (MRD) rate.
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Masking
NONE
Enrollment
26
Binary variable indicating if MRD was achieved.
Time frame: Approximately 3 years.
Isolated Central Nervous System (CNS) relapse rate.
Binary variable indicating if isolated CNS relapse occurred.
Time frame: 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 Absolute Neutrophil Count (ANC) ≥1000/μL and platelets ≥100,000/μL.
Time frame: 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
Time frame: Approximately 3 years.
Overall Response (OR) rate.
A binary variable indicating if a CR or CRi was achieved.
Time frame: Approximately 3 years.
Occurrence of toxicities per Common Terminology Criteria V5.0
Binary variables indicating the occurrence of toxicities per Common Terminology Criteria V5.0.
Time frame: Approximately 3 years.