The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia.
The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia. This study will investigate the combination of LP-118 and ponatinib at different dose levels to find the best doses that can be safely given to patients. This means that enrolled subjects will receive progressive increasing or decreasing doses of these drugs until the maximally tolerated dose is determined. All participants will also receive a standard of care chemotherapy combination consisting of the FDA approved drugs vincristine, dexamethasone and intrathecal (injection into the spinal canal, also called "spinal tap") methotrexate. This combination is standard of care for relapsed T-ALL/LBL.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
LP-118 is an experimental anti-cancer drug that is currently being studied in clinical trials for multiple types of hematological cancers and solid tumors.
Ponatinib is used to treat certain types of chronic myeloid leukemia (CML; a type of cancer of the white blood cells).
Vincristine is a chemotherapy medication used to treat various types of cancer, including leukemia, lymphoma, neuroblastoma, and Wilms tumor. Vincristine belongs to the category of vinca alkaloids, a class of drugs that function by impeding the proper division of cancer cells.
Dexamethasone is used to treat cancer, to decrease inflammation and sometimes used before and after chemotherapy to prevent or treat nausea and/or vomiting. It is given in the vein (IV) or orally (by mouth)
Methotrexate is a drug used to treat cancer of the blood, bone, lung, breast, head, and neck. It can also treat rheumatoid arthritis and psoriasis.
University of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, United States
RECRUITINGUniversity of Rochester Medical Center, Wilmot Cancer Center
Rochester, New York, United States
RECRUITINGRecommended Phase II Dose To demonstrate safety and to identify the recommended phase II dose for combination of LP-118, ponatinib, vincristine and dexamethasone
Recommended phase II dose for combination of LP-118, ponatinib, vincristine and dexamethasone as assessed by rate of dose-limiting toxicities among study participants.
Time frame: 36 weeks
Complete Clinical Remission at Days 28 and 56
Complete clinical remission at days 28 and 56 for study participants defined as the disappearance of leukemia as indicated by \<5% marrow blasts and the absence of peripheral blasts, with recovery of hematopoiesis defined by ANC ≥1000/μL and platelets ≥100,000/μL.
Time frame: 36 weeks
Complete clinical remission with incomplete count recovery (CRi) at Days 28 and 56
Complete clinical remission with incomplete count recovery (CRi) at day 28 and 56 for study participants treated at the recommended phase 2 (RP2D) dose level, defined as complete clinical remission except with ANC\< 1000/μL and/or platelets \<100,000/μL
Time frame: 36 weeks
Complete Clinical Remission (CR) with Measurable Residual Disease (MRD)
Complete clinical remission with measurable residual disease (MRD) negativity at day 28 and 56 for participants treated at the recommended phase 2 (RP2D) dose level.
Time frame: 36 weeks
Complete clinical remission with incomplete count recovery (CRi) with Measurable Residual Disease (MRD)
CRi with MRD negativity at days 28 and 56, defined by absence of detectable disease by flow cytometry (sensitivity of 0.01%), and V(D)J next-generation sequencing-based MRD assessment (sensitivity of 0.0001%)
Time frame: 36 weeks
Overall Survival
Overall survival (OS), defined as the time from treatment administration to death from any cause, or until last contact if the patient has not died.
Time frame: 36 weeks
Progression-Free Survival
Progression-free survival (PFS), defined as the time from treatment administration to documented disease progression or death from any cause, or until last contact if no event has occurred.
Time frame: 36 weeks
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