Venetoclax + Navitoclax for Acute Lymphoblastic Leukemia

Recruiting in Palo Alto (17 mi)

+1 other location

Seth Karol, MD - St. Jude Children's ...

Overseen bySeth E. Karol, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: St. Jude Children's Research Hospital

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This is a phase I/II clinical trial evaluating the activity of combination chemotherapy with venetoclax and navitoclax in children with relapsed or refractory acute lymphoblastic leukemia or lymphoma (rALL) and assessing the combination dose of venetoclax combinations with either blinatumomab for CD19-postive patients or navitoclax and high-dose cytarabine for CD19-negative patients. Primary Objectives * To compare Minimal Residual Disease (MRD)-negative CR/CRi rate in children with relapsed or refractory acute lymphoblastic leukemia or lymphoma (rALL) following Block 1 therapy with venetoclax and navitoclax based reinduction to historical controls. * To identify the recommended phase 2 combination dose (RP2D) of venetoclax based consolidation in novel combinations with a) high-dose cytarabine and navitoclax or b) blinatumomab. Secondary Objectives * To estimate the tolerability and activity of venetoclax based consolidation in novel combinations with a) high-dose cytarabine and navitoclax or b) blinatumomab. * To describe event-free and overall survival in patients treated with this regimen. Exploratory Objectives * To evaluate MRD-negative CR/CRi rates in each prespecified groups: late first relapse B-ALL; early first relapse and second or greater relapse B-ALL; and relapsed T-ALL. * To identify drug sensitivity patterns in patient samples prior to and after receiving combination therapy and evaluate mechanisms of disease resistance/ escape. * To explore immune subsets during and after this regimen. * Evaluate response to therapy in rare relapse patient subsets. * Explore breakthrough infections in children and young adults with relapsed or refractory ALL

Eligibility Criteria

This trial is for children and young adults aged 4 to under 30 with relapsed or refractory acute lymphoblastic leukemia/lymphoma. They must have certain levels of disease in the bone marrow or blood, be able to swallow pills, have no severe heart issues, and not have had certain recent treatments. Those with Down Syndrome are eligible only for specific parts of the study.

Inclusion Criteria

I am mostly able to do daily activities but need some help.

Specific criteria for patients with prior hematopoietic stem cell transplant

My leukemia or lymphoma has returned or didn't respond to treatment, with specific bone marrow involvement.

+9 more

Exclusion Criteria

I am currently taking certain medications or consuming specific foods.

Pregnant or lactating

Inability or unwillingness to give written informed consent

+1 more

Participant Groups

The trial tests a combination chemotherapy using venetoclax and navitoclax on patients with relapsed leukemia/lymphoma. It aims to find the best dose when combined with either blinatumomab (for CD19-positive patients) or high-dose cytarabine (for CD19-negative patients), comparing results against past data.

2Treatment groups

Experimental Treatment

Group I: Block 2Experimental Treatment17 Interventions

Block 2a Therapy: Patients receive intervention according to the Detailed Description section with the following: Venetoclax, Navitoclax, Dexamethasone, Cytarabine, Calaspargase Pegol, Pegaspargase, Erwinia asparaginase, Dasatinib, IT MHA, Radiation Block 2b Therapy: Patients receive intervention according to the Detailed Description section with the following: Venetoclax, Blinatumomab, Dexamethasone, Dasatinib, IT MHA Following Block 2 of therapy, late (≥36 months from diagnosis) first relapse B-ALL who are MRD negative after Block 1 will continue chemotherapy using adapted R3 intensification, interim, and continuation therapies. Patients receive intervention according to the Detailed Description section with the following: Methotrexate, Mercaptopurine, IT MHA, Leucovorin, Dexamethasone, Vincristine, Cyclophosphamide, Etoposide, Cytarabine, Dasatinib, Calaspargase Pegol, Pegaspargase, Erwinia asparaginase, Radiation

Group II: Block 1Experimental Treatment10 Interventions

All eligible patients receive intervention according to the Detailed Description section with the following: Venetoclax, Navitoclax, Dexamethasone, Vincristine, Calaspargase Pegol, Pegaspargase, Erwinia asparaginase, Dasatinib, Leucovorin, Intrathecal (IT) MHA (methotrexate/hydrocortisone/cytarabine)