A Phase II Study to Evaluate Safety and Efficacy of CB-103 in Combination With Venetoclax in Adolescent and Young Adult Patients With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL)
A Phase II Study to Evaluate Safety and Efficacy of CB-103 in Combination With Venetoclax in Adolescent and Young Adult Patients With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL)
To learn if the combination of 2 study drugs, CB-103 and venetoclax, can help to control T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic leukemia (T-LBL) in adolescent and young adult patients
Primary Objectives:
Secondary Objectives:
Exploratory Objectives:
Transplant (HSCT):
Inclusion Criteria:
however, a fresh marrow/blood sample must be obtained before starting the study treatment to classify the participants 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
Participants have adequate performance status (ECOG ≤2) for participants ≥16 years old, Lansky score >50 for patients <16 years old.
Participants must be 12 to 60 years of age inclusive when signing the informed consent. For participants < 18 years of age, parent or legally authorized representative (LAR) should be willing and able to give informed consent. Non-English speaking participants are eligible for whom consent process will follow institutional guidelines.
Participants with asymptomatic CNS disease are eligible
Participants must have adequate organ function and laboratory results (obtained within 14 days of enrollment):
Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (β-HCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug. Effective methods of birth control include:
Males agree to inform study doctor right away if their partner becomes pregnant or suspects pregnancy. While in this study and for 30 days after the last treatment the participant agrees not to donate sperm for the purposes of reproduction. He agrees to use a condom while in this study and for 30 days after the last treatment.
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. Participants 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.
Participants 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.
Medical history of cardiovascular disease such as
Participants with uncontrolled, active infections (viral, bacterial, or fungal). Infections controlled on concurrent anti-microbial agents are acceptable. Anti-microbial prophylaxis per institutional guidelines is acceptable.
Known active hepatitis B or C infection or known seropositivity for HIV.
Liver cirrhosis or other active severe liver disease or suspected active alcohol abuse.
Have conditions requiring chronic systemic (not inhaled) glucocorticoid use, such as autoimmune disease or severe asthma. Low doses of corticosteroids (10 mg prednisone equivalent a day) are permitted.
Participants with unresolved nausea, vomiting, or diarrhea of CTCAE version 5.0, grade ˃
1 from prior therapy.
Participants with impairment of GI function or GI disease presence that may significantly alter the absorption of CB-103 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
Have current or recurrent (within 3 months) gastrointestinal disease, have conditions requiring chronic systemic glucocorticoid use, have active graft versus host disease, or have a second primary or prior malignancy that would affect the interpretation of study results. Low doses of corticosteroids (10 mg prednisone equivalent a day) are permitted.
Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - Up to 5 days of glucocorticoids (10 mg of dexamethasone or equivalent/day) in combination with up to 3 doses of cyclophosphamide (200 mg/m2/day) are allowed as standard pre-phase treatment up to 1 day before start of study treatment.
Cytarabine up to 2gm/m2 are also allowed as standard pre-phase treatment up to 1 day before start of study treatment.
Mercaptopurine may be dosed up to 5 days prior to first dose of CB103
Vinca alkaloids may be dosed up to 5 days prior to first dose of CB103
Prophylactic intrathecal (IT) chemotherapy may be dosed up to 1 day prior to first dose of CB103
• Females who are pregnant or lactating
Male or female participants of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with institution's standards.
Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the Investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.
Participants who are unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures.
Participants must be excluded if they are currently enrolled in another ongoing clinical trial with anti-cancer investigational products