A Phase I/II Study to Investigate the Combination of LP-118, Ponatinib, Vincristine and Dexamethasone in Relapsed/Refractory T-ALL/LBL

Plain English Summary

A Study to Investigate LP-118, Ponatinib, Vincristine and Dexamethasone in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL) is a Phase 2 clinical trial sponsored by University of Chicago studying Acute Leukemia, Lymphoblastic Leukemia, Lymphoblastic Lymphoma. This trial tests a new combination of drugs (LP-118, ponatinib, vincristine, and dexamethasone) for patients with T-cell acute lymphoblastic leukemia or lymphoma that has returned or not responded to treatment. It is for adults (18+) with relapsed or refractory T-lineage acute lymphoblastic leukemia or T-lymphoblastic lymphoma. Participation involves receiving the study drugs and attending regular clinic visits for monitoring and tests. Alternative treatments may include other chemotherapy regimens, targeted therapies, or stem cell transplant, depending on the patient's specific situation and prior treatments. The trial aims to enroll 15 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with T-lineage acute lymphoblastic leukemia or T-lymphoblastic lymphoma that has relapsed or is refractory. Patients must have a certain level of leukemia cells in their bone marrow, blood, or measurable extramedullary disease. Individuals with active central nervous system leukemia, certain infections (like active hepatitis B or C, or HIV unless undetectable viral load), or severe uncontrolled medical conditions cannot participate. Participants must have adequate organ function and be able to comply with study requirements. This trial is studying Acute Leukemia, Lymphoblastic Leukemia, Lymphoblastic Lymphoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the safety of the new drug combination and helps determine the best dose for future studies, aiming to find a tolerable and effective treatment for patients. The specific primary outcome measures are: Recommended Phase II Dose To demonstrate safety and to identify the recommended phase II dose for combination of LP-118, ponatinib, vincristine and dexamethasone (36 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for new treatments for patients with relapsed or refractory T-ALL/LBL, a challenging subset of leukemia/lymphoma with limited effective options. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Acute Leukemia, Lymphoblastic Leukemia, Lymphoblastic Lymphoma, where improved treatment options are needed.

Investor Insight

This trial investigates a novel combination therapy for a rare and aggressive form of leukemia/lymphoma, potentially offering a new treatment avenue and representing an investment in a niche but high- Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of each drug in the combination, and how this trial compares to standard treatment options. Participation will involve regular clinic visits for drug administration, blood tests, imaging scans, and monitoring for side effects. Be prepared for potential side effects and discuss any new or worsening symptoms with your healthcare team immediately. This trial is currently recruiting participants. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 15 participants

Interventions

• DRUG: LP-118 — 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.
• DRUG: Ponatinib — Ponatinib is used to treat certain types of chronic myeloid leukemia (CML; a type of cancer of the white blood cells).
• DRUG: Vincristine — 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.
• DRUG: Dexamethasone — 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)
• DRUG: Methotrexate — 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.

Primary Outcomes

• Recommended Phase II Dose To demonstrate safety and to identify the recommended phase II dose for combination of LP-118, ponatinib, vincristine and dexamethasone (36 weeks)

Secondary Outcomes

• Complete Clinical Remission at Days 28 and 56 (36 weeks)
• Complete clinical remission with incomplete count recovery (CRi) at Days 28 and 56 (36 weeks)
• Complete Clinical Remission (CR) with Measurable Residual Disease (MRD) (36 weeks)
• Complete clinical remission with incomplete count recovery (CRi) with Measurable Residual Disease (MRD) (36 weeks)
• Overall Survival (36 weeks)

Full Eligibility Criteria

Inclusion Criteria:

1. Relapsed or refractory patients with T-lineage acute lymphoblastic leukemia or T-lymphoblastic lymphoma
2. 18 years old or older
3. Bone marrow or peripheral blood involvement with ≥5% lymphoblasts or measurable residual disease with \>10-4 level detected by multiparameter flow cytometry or next-generation sequencing (NGS)-based measurable residual disease (ClonoSEQ, Adaptive Technologies). Patients with isolated extramedullary disease that is measurable by computed tomography (CT) scan are also eligible.
4. Eastern Cooperative Oncology Group performance status 0-2.
5. Adequate organ function as defined by all of the following:

   1. Creatinine clearance ≥50 mL/min, determined by the Cockroft-Gault formula, or measured by a 24-hour urine collection.
   2. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN) and bilirubin ≤1.5 x ULN (unless 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.
6. Participants must be at least 2 weeks from major surgery or radiation therapy. A wash-out period of 4 half-lives is required for patients who participated in other investigational trials. These patients must have recovered from clinically significant toxicities related to these prior treatments.
7. Participants must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
8. Females of childbearing potential will use effective contraception during protocol treatment and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during protocol treatment and for at least 5 months after the last dose. A patient is of childbearing potential if, in the opinion of the treating investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria):

   a. Have undergone hysterectomy or bilateral oophorectomy; or have medically confirmed ovarian failure; or are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).
9. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Active central nervous system (CNS) leukemia
2. Active or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). Patients with HIV but an undetectable viral load are eligible for enrollment.
3. Major surgery within \<2 weeks before randomization.
4. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition.
5. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for ≥2 years or are not currently requiring treatment.
6. Uncontrolled cardiac disease.
7. Pregnant females; breastfeeding females; males with female partners of reproductive potential and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for a minimum of 5 months after the last dose of investigational product if male and 8 months after the last dose of investigational product if female.
8. Participation in other investigational studies during active treatment phase.
9. Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the treating physician, would make the patient inappropriate for entry into this study.

Trial Locations

• University of Chicago Medicine Comprehensive Cancer Center, Chicago, Illinois, United States
• University of Rochester Medical Center, Wilmot Cancer Center, Rochester, New York, United States

Frequently Asked Questions

Related Conditions

• Acute Lymphoblastic Leukemia (ALL)
• T-cell Acute Lymphoblastic Leukemia (T-ALL)
• Lymphoblastic Lymphoma (LBL)
• Relapsed Leukemia
• Refractory Leukemia
• Hematologic Malignancies
• Leukemia
• Lymphoma
• Oncology
• Cancer Therapeutics

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