A First in Human, Phase 1, Open-Label Study on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 4A10 Monotherapy In Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Summary
ALT-101 is a first-in-human Phase 1 clinical trial testing a new antibody drug called 4A10 in patients with relapsed or hard-to-treat acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. 4A10 is a targeted therapy designed to recognize and attach to a specific protein (CD127) found on leukemia cells. Once it binds, it works in two ways: it blocks growth signals that help cancer cells survive, and it helps the immune system find and destroy those cancer cells. In this study, patients receive 4A10 through an intravenous (IV) infusion once a week. The main goal of the trial is to find out if the drug is safe, what dose can be given, and how the body processes it. Researchers will also look for early signs that the treatment may be working. The study starts with small groups of patients receiving increasing doses to carefully monitor safety. Each patient is closely observed during the first treatment cycle (about 4-6 weeks) to watch for side effects. If the treatment is helping and is well tolerated, patients may continue treatment for up to six cycles. Overall, this study is an early step in testing a new, targeted immune-based therapy for difficult-to-treat blood cancers.
Arms & interventions
- Drug4A10
4A10 (Molecule B4532) is an investigational human Immunoglobulin G Subclass 1 (IgG1) monoclonal antibody that specifically binds CD127 (Interleukin-7 receptor alpha subunit, IL-7Rα). CD127 is a component of the interleukin-7 receptor and the thymic stromal lymphopoietin receptor (TSLPR), which are expressed on T-cell acute lymphoblastic leukemia (T-ALL) and pre-B-cell acute lymphoblastic leukemia (B-ALL) cells.
Outcome measures
Primary
Incidence of Treatment-Emergent Adverse Events (TEAEs) at each dose level
Assessment of safety and tolerability of 4A10 as measured by the incidence, severity, and relationship of treatment-emergent adverse events, as graded by CTCAE v6, in participants receiving study treatment at each dose-level in the 3+3 dose escalation study design.
Time frame: Through study duration, an average of 1 year
Determine the Recommended Phase 2 Dose (RP2D)/ Recommended Dose for Expansion (RDE) of 4A10 as a single agent in patients with R/R ALL/LL.
Determination of the RP2D/RDE of ALT-101 based on evaluation of safety, tolerability, and available pharmacokinetic and pharmacodynamic data following dose-escalation.
Time frame: Through study duration, an average of 1 year
Secondary
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Time frame: Through study duration, an average of 1 year
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Time frame: Through study duration, an average of 1 year
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Time frame: Through study duration, an average of 1 year
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Time frame: Through the study duration, an average of 1 year.
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Time frame: Through the study duration, an average of 1 year
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Time frame: Through the study duration, an average of 1 year
Determine the Pharmacokinetics of 4A10 as a single agent in patients with Relapsed/Refractory ALL/LL.
Time frame: Through the study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Time frame: Through study duration, an average of 1 year.
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Time frame: Through study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Time frame: Through study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Time frame: Through study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Time frame: Through study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL.
Time frame: Through the study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL
Time frame: Through study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL
Time frame: Through study duration, an average of 1 year
Preliminary anti-tumor activity of 4A10 as a single agent in patients with refractory/ relapsed ALL or LL
Time frame: Through study duration, an average of 1 year
Eligibility criteria
Study locations (4)
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Cook Children's Medical Center
Fort Worth, Texas, 76104
Texas Children's Hospital
Houston, Texas, 77030