An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in P… (NCT03779113) | Clinical Trial Compass
TerminatedPhase 1
An Open-label, Dose Escalation Trial to Evaluate the Safety and Pharmacokinetics of HMPL-523 in Patients With Lymphoma
Stopped: Study terminated by sponsor
United States69 participantsStarted 2019-09-26
Plain-language summary
This is a Phase I, open-label, multicenter study of HMPL-523 administered orally to patients with relapsed or refractory lymphoma who have exhausted approved therapy options. This study consists of a dose escalation stage (Stage1) and a dose expansion stage (Stage 2).
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Signed informed consent form (ICF).
✓. Age ≥18 years.
✓. ECOG performance status of 0 or 1.
✓. Histologically confirmed lymphoma, including Hodgkin's lymphoma and non-Hodgkin's lymphoma. In the dose expansion stage, the tumor types may be restricted to any or all of the following tumor types. There may be approximately 10 patients in each cohort depending on response signals suggesting efficacy, except for 2 identified cohorts with approximately 20 patients per cohort: relapsed or refractory CLL/SLL, CLL/SLL post-BTK exposure (n=20), MCL, FL (Grade 1-3a) (n=20), MZL, WM/LPL, PTCL,CBCL, and/or HL
✓. Patients with relapsed or refractory lymphoma who have exhausted all approved therapy options.
✓. In the dose expansion stage, patients must have measurable disease for an objective response assessment, except for patients with CLL and WM/LPL
✓. Availability of tumor sample for patients in dose expansion cohorts: This may be an archival tissue sample obtained after most recent therapy or a fresh biopsy; if tumor sample is not available, the Sponsor may waive the requirement after discussion
✓. Expected survival of more than 24 weeks as determined by the investigator.
Exclusion criteria
✕. Patients with primary central nervous system (CNS) lymphoma.
✕. Any of the following laboratory abnormalities: Absolute neutrophil count\<1.0×10\^9/L, Hemoglobin \<80 g/L, Platelets \<50×10\^9/L
What they're measuring
1
Dose Escalation Stage: Number of Patients With Dose-Limiting Toxicities (DLTs)
Timeframe: From the first dose of study treatment (Day 1) up to Day 28 of Cycle 1 (each cycle was 28 days)
2
Dose Escalation Stage: Number of Patients With Treatment-Emergent Adverse Events, Treatment Related Treatment-Emergent Adverse Events, Treatment-Emergent Adverse Events Leading to Treatment Interruption, Treatment Reduction and Treatment Discontinuation
Timeframe: From the first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment, approximately 29 months
3
Dose Escalation Stage: Recommended Phase 2 Dose of HMPL-523
Timeframe: From the first dose of study treatment (Day 1) up to Day 28 of Cycle 1 (each cycle was 28 days)
Timeframe: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter until first progression, initiation of new anticancer therapy or death. Approximately 42 months
5
Dose Expansion Stage: Complete Response Rate
Timeframe: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter until first progression, initiation of new anticancer therapy or death. Approximately 42 months
✕. Inadequate organ function, defined by the following: Total bilirubin \>1.5 times the upper limit of normal (× ULN), aspartate aminotransferase and/or alanine aminotransferase \>2.5 × ULN, Estimated Creatinine Clearance (CrCl) per Cockcroft-Gault \[Dose Escalation portion of trial (Stage 1) CrCl \< 40 mL/min, Dose Expansion portion of trial (Stage 2) CrCl \< 30 mL/min\], Serum amylase or lipase \>ULN, International normalized ratio \>1.5 × ULN, or activated partial thromboplastin time \>1.5 × ULN
✕. Patients with clinically detectable second primary malignant tumors at enrollment or other malignant tumors within the last 2 years (with the exception of radically treated basal cell or squamous cell carcinoma of the skin, in situ cervix, or in situ breast cancer).
✕. Any anticancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine, or radiotherapy within 3 weeks prior to the initiation of study treatment.
✕. Herbal therapy within 1 week prior to the initiation of study treatment.
✕. Prior use of any anti-cancer vaccine
✕. Prior treatment with any spleen tyrosine kinase (SYK) inhibitors (eg, fostamatinib)
Timeframe: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter until first progression, initiation of new anticancer therapy or death. Approximately 42 months
7
Dose Expansion Stage: Duration of Response (DOR)
Timeframe: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter until first progression, initiation of new anticancer therapy or death. Approximately 42 months
8
Dose Expansion Stage: Time to Response (TTR)
Timeframe: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter until first progression, initiation of new anticancer therapy or death. Approximately 42 months
Timeframe: Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-7 days) thereafter until first progression, initiation of new anticancer therapy or death. Approximately 42 months