Acute Myeloid Leukemia (AML)
Conditions
Keywords
CBFA2T3::GLIS2 Fusion, CBFA2T3::GLIS2 AML, RAM Phenotype (CD56pos); CD45, CD38, HLA-DR weak or absent), REFRaME, AML, Child, Pediatric AML, REFRaME-P1, Luveltamab, tazevibulin, STRO-002
Brief summary
This trial will evaluate whether luveltamab tazevibulin is well tolerated and active against a rare form of AML carrying a particular genetic abnormality called CBFA2T3::GLIS2 that arises in infants and children. To be treated in this trial children must have a leukemia which did not respond or recurred after prior treatment. Luveltamab tazevibulin is an antibody-drug conjugate, which brings tazevibulin, an anticancer drug, to a molecule called FOLR1, present on the surface of CBFA2T3::GLIS2 AML cells.
Detailed description
This is a registrational international, multicenter, two-part open label Phase 1/2 trial in an extremely rare pediatric disease (around 17 new patients a year in US and 10 in EU). Part 1 randomizes subjects 1:1 to one of two luveltamab tazevibulin dose cohorts (1a and 1b). Part 2 further evaluates the safety and the efficacy of the selected dose. Subjects who achieve complete remission after two cycles of treatment may continue luveltamab tazevibulin as monotherapy, while non-responders at PI discretion may add luveltamab tazevibulin with standard of care (SOC) AML treatments. Luveltamab tazevibulin is given IV every two week as monotherapy and every 4 weeks when given with chemotherapy.
Interventions
Luveltamab tazevibulin is an antibody-drug conjugate (ADC) targeting folate receptor α (FRα or FOLR1). It consists of an IgG1 antibody (SP8166) conjugated to cathepsin cleavable 3-aminophenyl hemiasterlin payload, yielding a homogenous ADC with a drug antibody ratio of four. The active warhead (SC209) inhibits tubulin polymerization leading to mitotic arrest and cell death. Other Names: * STRO-002 * Luvelta
Sponsors
Children's Oncology Group
Innovative Therapies For Children with Cancer Consortium
Sutro Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This trial has two parts, Part 1 will use a parallel model by assessing two luveltamab tazevibulin doses (3.5 and 4.3 mg/kg every 2 weeks). Two cohorts will be run in parallel. The transition from part 1 to part 2 is sequential, with part 2 testing the dose selected at the end of part 1.
Eligibility
Sex/Gender
ALL
Age
1 Days to 12 Years
Healthy volunteers
No
Inclusion criteria
* AML with CBFA2T3::GLIS2 gene fusion centrally confirmed * Refractory or relapsed disease with ≥ 5% bone marrow involvement with leukemic blasts by morphology * Age \< 12 years. * Lansky performance of ≥ 50 * Adequate organ functions
Exclusion criteria
* Active central nervous system (CNS) disease (CNS3) * Pre-existing clinically significant corneal disorders or constitutional diseases associated with an increased risk of AML treatment toxicities * Active or uncontrolled infections or other active severe intercurrent illnesses, * Prior treatment with a FOLR1- targeting ADCs or with ADCs that contain a tubulin inhibitor * History of allogeneic hematopoietic stem cell transplant or any organ transplant in the prior 84 days * Graft versus host disease (GVHD) of any grade or GVHD treatment with exception of low dose steroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate efficacy of luveltamab tazevibulin monotherapy | Up to 12 weeks | Complete remission rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess additional efficacy outcome measures | Up to 2 years | • Duration of CR |
| Evaluate safety measures | Up to 2 years | Incidence and severity of AEs and clinical laboratory abnormalities per NCI CTCAE v5.0 in patients receiving luveltamab tazevibulin monotherapy. |
| To characterize the PK of luveltamab tazevibulin | Up to 2 years | Concentration of luveltamab tazevibulin (ADC, TAb, and SC209) in the blood. |
| Assess the immunogenic potential of luveltamab tazevibulin | Up to 2 years | Incidence of ADAs |
Countries
Austria, Canada, Denmark, France, Germany, Italy, Netherlands, Spain, United States
Outcome results
None listed