A Study of FCN-338 in Patients With Chronic CLL/SLL

NCT04682808 | Active Not Recruiting Phase 1

• 1 other identifier: FCN-338-002
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to evaluate the Tolerability、Pharmacokinetics and Preliminary antitumor activity of oral FCN-338 for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have failed or are intolerant to one or more lines of established therapy or for whom no other treatment options are available.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

BCL-2; CLL; SLL

Outcome Measures

Primary Outcomes (4)

• The occurrence of treatment-related adverse events meeting the criteria for dose limiting toxicities (DLTs)

  Cycle 1 (28 days)

• To establish the recommended MTD dose and Phase 2 dose (RP2D) of FCN-338 for future clinical trials in patients with advanced CLL/SLL

  Up to 24 months

• The occurrence of adverse events (AEs) reported in all subjects who received study drug

  From enrollment up to 30 days after last dose

• The occurrence of treatment-emergent adverse events (TEAs)

  From first dose up to 30 days after last dose

Secondary Outcomes (7)

• Pharmacokinetic variables including maximum plasma concentration (Cmax)

  Cycle 1 (28 days)

• Pharmacokinetic variables including minimum plasma concentration (Cmin)

  Cycle 1 (28 days)

• To quantify the last time point with a quantifiable concentration (AUClast) of FCN-338

  Cycle 1 (28 days)

• To measure the time to reach the highest plasma concentrations (Tmax) of FCN-338

  Cycle 1 (28 days)

• To quantify the terminal half-life (T1/2) of FCN-338 after administration as a single agent

  Cycle 1 (28 days)

Study Arms (1)

Dose Escalation and Expansion

EXPERIMENTAL

FCN-338 will be given orally in ascending doses in patients with relapsed or refractory CLL/SLL , until the maximum tolerated dose or recommended dose is reached. Followed by up to 43 patients enrolled in the expansion cohort at the recommended dose.

Drug: FCN-338

Interventions

FCN-338 DRUG

FCN-338 will be given orally in ascending doses starting at 50 mg QD until the maximum tolerated dose or recommended dose is reached.

Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years，no gender limitation；
• According to the 2018 iwCLL guidelines ，diagnosed as chronic lymphocytic leukemia or small cell lymphoma;
• Refractory or recurrent CLL/SLL having previously received at least first-line systemic treatment. First-line treatment is defined as the completion of at least 2 cycles of a standard protocol or clinical trial based on current guidelines. Medical record of disease progression after the last treatment failed or remission. According to the 2018 iwCLL guidelines, there are at least one CLL/SLL indications that require treatment. \[Refractory definition: treatment failure (without PR) or PD \< 6 months after the last chemotherapy); Definition of recurrence: Patients with complete response (CR) or partial response (PR) ≥ 6 months after disease progression (PD)\];
• ECOG Performance Status scored ≤ 1 （Dose Escalation Stage）or ≤ 2（Dose Expansion Stage）；
• The expected survival is at least 3 months;
• Adequate hematologic、renal function parameters；
• If patient have a high risk of developing TLS, The absolute lymphocyte count was ≥ 25× 109/L and there was a lymph node with a maximum diameter ≥ 5 cm assessed by radiology or there was a node with a maximum diameter ≥ 10 cm assessed by radiology ，patient must deal with TLS according to the protocol；
• For fertile patients: the patient shall consent to effective contraception during the treatment period and for at least 90 days after the last administration of the study treatment, and to receive contraceptive methods such as double-screen contraception, condoms, oral or injectable contraceptives, and intrauterine devices. Male patients should agree to avoid sperm donation;
• Patients voluntarily signed informed consent;

You may not qualify if:

• The patient's prior antitumor therapy meets one of the following criteria:
• Use of other cytotoxic drugs, research drugs or other antitumor drugs within 14 days or 5 half-lives before first receiving study drugs;
• Major surgery was performed within 4 weeks prior to the first receiving study drug or had not fully recovered from previous surgery；
• Systemic radiotherapy was performed within 28 days prior to the first dose of the study drug, or non-hematological toxicity has not recovered from previous radiotherapy to NCI-CTCAE (version 5.0) level 0-1;
• Received anti-tumor monoclonal antibody therapy within 4 weeks before receiving the first study drug;
• The toxicity of previous antitumor therapy has not recovered (≥ NCI-CTCAE \[version 5.0\] level 2), except for hair loss;
• Received steroid therapy for antitumor within 7 days before first receiving study drug;
• Has received allogeneic stem cell transplantation or autologous stem cell transplantation within 6 months prior to first receiving research drug；
• The biopsy confirmed the transformation to Richter's syndrome；
• Drug resistance to another bcl-2 family protein inhibitor has occurred (for extend study use only)；
• Cardiac function and disease meet one of the following conditions:
• The prolonged QTc interval has clinical significance, or the screening stage QTc interval is \>470ms for women or \>450ms for men；
• American New York Heart Association (NYHA) grade ≥ 2 congestive Heart failure;
• Unstable angina, myocardial infarction, or arrhythmia requiring treatment during screening, Left ventricular ejection fraction (LVEF) \<50%; Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmia-causing right ventricular cardiomyopathy, restricted cardiomyopathy, unformed cardiomyopathy);
• The investigators determined that the patient's cardiac function can't tolerate to TLS prophylaxis；

Sponsors & Collaborators

• Fochon Pharmaceuticals, Ltd.: lead

Study Sites (1)

SUN YAT-University Cancer Center

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Huang Hui Qiang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: December 24, 2020
• Study Start: May 13, 2021
• Primary Completion: April 28, 2024
• Study Completion: December 31, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)