A Phase 1 Study to Evaluate the Safety and Tolerability of TT-01488 in Patients With B-Cell Malignancies

Trial Title: A Phase 1 Study to Evaluate the Safety and Tolerability of TT-01488 in Patients With B-Cell Malignancies

NCT ID: NCT05683717

Condition: B-Cell Malignancies

Conditions: Official terms:
Neoplasms

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: TT-01488 Tablets
Description: TT-01488 tablet will be administered orally once daily per protocol defined schedule.
Arm group label: Dose Escalation for TT-01488
Arm group label: Dose Expansion for TT-01488

Summary: This is a multicenter, open-label Phase I dose escalation study to evaluate the safety and preliminary efficacy of the TT-01488 tablet, a non-covalent reversible BTK inhibitor, for the treatment of adult patients with B-cell malignancies.

Detailed description: The study will consist of two parts, dose escalation and dose expansion. A modified 3+3 design will be used to guide the dose escalation and the determination of the dose recommended for dose expansion (DRDE). A sentinel cohort comprising of one subject will be enrolled at a starting dose of 50 mg q.d. Subsequently, patients will be enrolled according to the standard 3+3 dose escalation design to determine the DRDE. Once the DRDE has been selected, TT-01488 of DRDE will be further tested in the dose expansion cohort to verify the safety and preliminary efficacy as observed in the dose escalation cohorts. A recommended Phase II dose (RP2D) may be determined based on the totality of safety, pharmacokinetics, and efficacy data from the dose escalation cohorts and dose expansion cohort.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Participants with histologically confirmed B-cell malignancy, failed or intolerant to either ≥ 2 prior standard/common regimens given in combination or sequentially OR have received 1 prior BTK-containing regimen, relapse/refractory, and with treatment indication: - CLL/SLL treated with prior immunochemistry or BTK inhibitor containing regimen; - DLBCL treated with prior CD20 or anthracyclines containing regimen; - Other types of B-cell NHL treated with prior CD20 containing regimen - Adequate organ function, defined by the following laboratory parameters: - Hematologic: - Absolute neutrophil count (ANC) ≥ 0.75×10^9/L, and ≥ 0.5×10^9/L if bone marrow involved - Platelets ≥ 50×10^9/L without transfusion within 7 days, and ≥ 30×10^9/L if bone marrow involved - Hemoglobin ≥ 8.0 g/dL without transfusion within 7 days, and ≥ 7.0 g/dL if bone marrow involved - Coagulation: - Prothrombin time (PT) ≤ 1.5 × ULN - Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN - Renal function: - Creatinine clearance ≥ 30 mL/min estimated glomerular filtration rate based on Cockcroft-Gault formula - Liver function: - Total bilirubin ≤ 1.5 × ULN (unless due to Gilbert's disease) - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN unless disease-related Exclusion Criteria: - Women who are pregnant or lactating - Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years or which will not limit survival to < 2 years (Note: these cases must be discussed with the Medical Monitor and/or Investigator) - Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or significant screening ECG abnormalities - Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction - History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 60 days or with any of the following: - Active graft versus host disease (GvHD); - Cytopenias from incomplete blood cell count recovery post-transplant; - Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy; - Ongoing immunosuppressive therapy - Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy, including radiation

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: The First Affiliated Hospital with Nanjing Medical University

Address:
City: Nanjing
Zip: 210000
Country: China

Status: Recruiting

Contact:
Last name: Jianyong Li, M.D.
Email: lijianyonglm@126.com

Contact backup:
Last name: Wei Xu, M.D.
Email: xuwei10000@hotmail.com

Start date: March 30, 2023

Completion date: October 30, 2028

Lead sponsor:
Agency: TransThera Sciences (Nanjing), Inc.
Agency class: Industry

Source: TransThera Sciences (Nanjing), Inc.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05683717