Phase II Study to Evaluate Safety and Efficacy of CB-103 With Venetoclax in Adolescent and Young Adult Patients With Relapsed/Refractory T-ALL or T-LBL

This is an interventional treatment trial for Leukemia, Lymphoblastic Read More

• Inclusion Criteria:

Adolescent (12 to 18 years), and young adult (19 to 40 years) patients who have relapse or refractory T-cell lymphoblastic leukemia (T-ALL) or T-Cell lymphoblastic lymphoma (T-LBL) according to 2017 WHO classification [29] and NCCN v1 2021 [30]:

Patients must have ≥ 5% blasts in the bone marrow as assessed by morphology on standard bone marrow biopsy and aspirate or less than 5% blasts in the bone marrow in presence of extramedullary relapse, excluding isolated central nervous system (CNS) relapse. However, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood.

Patients are eligible independently of Notch pathway activation in the leukemic blasts: However, a fresh marrow/blood sample must be obtained before starting the study treatment to classify the patients as being either Notch positive or negative.

Leukemic blasts must express of at least 2 of the following immune phenotyping: CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD34, TCRαβ, TCRγδ, cyCD3

Patients have adequate performance status (ECOG ≤2) for patients ≥16 years old, Lansky score >50 for patients <16 years old. Patients have a life expectancy of at least 4 months. Patients must be 12 to 40 years of age inclusive when signing the informed consent.

Patients with asymptomatic CNS disease are eligible

• Exclusion Criteria:

Mixed phenotype leukemia (excluding T-ALL with myeloid antigen expression)

History of another primary invasive malignancy that has not been definitively treated and in remission. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).

Presence of clinically significant uncontrolled CNS pathology such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or psychosis.

Evidence of active cerebral/meningeal disease. Patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of consent (see inclusion criterion 3.1.7.).

Patients with a cardiac ejection fraction (as measured by either MUGA or echocardiogram) < 50% or with a history of absolute decrease in LVEF of ≥ 15 absolute percentage points are excluded.

Patients with uncontrolled, active infections (viral, bacterial, or fungal). Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.

Known active hepatitis B or C infection or known seropositivity for HIV.

Liver cirrhosis or other active severe liver disease or with suspected active alcohol abuse.

Patients with impairment of GI function or GI disease presence that significantly alter the absorption of CB-103 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).

Females who are pregnant or lactating.