A Study of AC676 for the Treatment of Relapsed/Refractory B-Cell Malignancies
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: AC676.
- Who it may be relevant to
- Registry conditions: Relapsed/Refractory B-cell Malignancies. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase I Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Malignancy Activity of AC676 in Patients With Relapsed/Refractory B-cell Malignancies
Overview
This clinical trial is evaluating a drug called AC676 in participants with Relapsed/Refractory B-cell Malignancies. The main goals of the study are to: * Identify the recommended dose of AC676 that can be given safely to participants * Evaluate the safety profile of AC676 * Evaluate the pharmacokinetics of AC676 * Evaluate the effectiveness of AC676
Detailed description
AC676-001 is a Phase I, first-in-human, open-label, multi-center dose-escalation study of AC676 given as a single agent. AC676 is an investigational medicinal product that is an orally bioavailable BTK degrader for the treatment of B-cell malignancies.
Interventions
- Drug AC676
AC676 will be given orally (PO) on a 28-day cycle.
Primary outcome measures
- Incidence of dose limiting toxicities (DLTs) from AC676 monotherapy [Time frame: From cycle 1 day 1 to Cycle 1 day 28. Cycles are 28 days.]
- Incidence of treatment-emergent adverse events (TEAEs) and clinically significant Grade 3 or higher laboratory abnormalities using CTCAE v5.0 criteria. [Time frame: Approximately 18 months]
- Maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) [Time frame: Approximately 18 months]
Secondary outcome measures (10)
- Pharmacokinetic Analysis: area under the plasma concentration-time curve over the dosing interval (AUC(0-inf)) [Time frame: Up to approximately 20 weeks]
- Pharmacokinetic Analysis: area under the plasma concentration-time curve from over the dosing interval (AUC(0-tau)) [Time frame: Up to approximately 20 weeks]
- Pharmacokinetic Analysis: maximum plasma concentration (Cmax) [Time frame: Up to approximately 20 weeks]
- Pharmacokinetic Analysis: time to maximum plasma concentration (tmax) [Time frame: Up to approximately 20 weeks]
- Pharmacokinetic Analysis: terminal elimination half-life (t1/2) [Time frame: Up to approximately 20 weeks]
- Objective Response Rate (ORR) in patients receiving AC676 [Time frame: Approximately 18 months]
- Duration of Response (DOR) in patients receiving AC676 [Time frame: Approximately 18 months]
- Time to Response (TTR) in patients receiving AC676 [Time frame: Approximately 18 months]
- Disease Control Rate (DCR) in patients receiving AC676 [Time frame: Approximately 18 months]
- Progression Free Survival rate (PFS) in patients receiving AC676 [Time frame: Approximately 18 months]
Eligibility criteria
Inclusion criteria
- Adult male and female patients, at least 18 years-of-age at the time of signature of the informed consent form (ICF).
- Patients with histologically confirmed relapsed/refractory Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL), non-GCB Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL), or Waldenström Macroglobulinemia (WM).
- Must have received at least 2 prior systemic therapies or have no other therapies to provide significant clinical benefit in the opinion of the Investigator or who are not amenable (intolerability, patient choice) to standard therapies.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry:
- Treatment with any of the following:
- Small molecule anti-cancer drugs within 5 half-lives or 2 days (whichever is longer, not to exceed 14 days).
- Systemic chemotherapy within 14 days.
- Radiation therapy within 14 days
- Biologics (Antibodies) treatment within 28 days,
- Radioimmunoconjugates or toxin conjugates within 12 weeks.
- Prior Chimeric antigen receptor (CAR) T cell therapy (and prior use of immunoglobulin replacement therapy to treat associated adverse events) within 3 months. For patients with DLBCL, no prior CAR- T therapy is allowed.
- Autologous or allogenic stem cell transplant within 100 days and must not have ongoing graft-versus-host disease (GVHD) and no ongoing therapy to treat GVHD.
- History of central nervous system lymphoma/leukemia in remission for less than 2 years.
- Medical history of active bleeding within 2 months prior to study entry, or susceptible to bleeding by the judgement of investigator.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 9 centers
- Colorado Blood Cancer Institute — Denver
- Florida Cancer Specialists — Sarasota
- University of North Carolina — Chapel Hill
- University Hospitals Cleveland Medical Center — Cleveland
- The Ohio State University - The James Cancer Hospital and Solove Research Institute — Columbus
- Oregon Health & Science University — Portland
- Tennessee Oncology — Nashville
- University of Texas Southwestern Medical Center — Dallas
- … and 1 more center
Identifiers
NCT: NCT05780034 · AC676-001