Investigating a new drug combination for relapsed acute lymphoblastic leukemia

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

This study is testing a new combination of drugs to see if it can safely help patients with relapsed acute lymphoblastic leukemia feel better and improve their treatment outcomes.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Chicago (other)
• Drugs / interventions: radiation, ponatinib, chemotherapy, methotrexate
• Locations: 2 sites (Chicago, Illinois and 1 other locations)
• Trial ID: NCT06207123 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and efficacy of LP-118, an experimental drug, in combination with ponatinib, an FDA-approved treatment for acute lymphoblastic leukemia. Participants will receive varying doses of these medications to determine the maximum tolerated dose while also receiving standard chemotherapy with vincristine, dexamethasone, and methotrexate. The study focuses on patients with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma. The goal is to find a safe and effective treatment regimen for these challenging cases.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma.

Not a fit: Patients with other types of leukemia or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with relapsed or refractory acute lymphoblastic leukemia.

How similar studies have performed: Other studies have shown promise in combining targeted therapies with standard chemotherapy for acute lymphoblastic leukemia, suggesting potential for success in this approach.

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.

Where this trial is running

Chicago, Illinois and 1 other locations

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

Study contacts

• Study coordinator: Caner Saygin, MD

Conditions: Acute Leukemia, Lymphoblastic Leukemia, Lymphoblastic Lymphoma