Safety Study of CC312 in Adult Patients With Relapsed/Refractory CD19 Positive B-cell Hematologic Malignancies
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCytoCares Inc
About this trial
This is a Phase 1, open-label, dose-escalation study to evaluate the safety, PK, PD and immunogenicity of CC312 following intravenous doses of CC312 in patients with relapsed and refractory (r/r) CD19 expressing B-cell non-Hodgkin lymphoma and B-cell lymphocytic leukemia.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
CD19 positive B-cell malignancies confirmed as one of the following: aggressive or indolent B-cell NHL, philadelphia chromosome-positive or -negative B-cell ALL, or B-cell CLL; patient must meet the definition of relapse/refractory before enrollment.
ECOG (Eastern Cooperative Oncology Group) performance status 0-2, life expectancy >3 months；
Clinical laboratory values as specified below during the Screening period.
Total bilirubin <1.5 ULN, may be elevated up to 3 x ULN if the elevation can be reasonably ascribed to the presence of metastatic disease in the liver or in patients with documented Gilbert's Syndrome;
Disqualifiers
Systemic anticancer therapy within 5 half-lives of the agent or attending clinical trials 4 weeks prior to beginning CC312;
Treatment with radiotherapy within 2 weeks before the study entry;
Treatment with CAR-T within 3 months before the study entry;
Active serious infection requiring antibiotics within 14 days before study entry;
Trial design
Design model
Single group
Treatments tested in this trial
CC312
Biological/VaccineDoses from 0.3 to 45 µg/dose by intravenous infusion
Treatment groups
44 Participants
are divided into 1 treatment groupGroup A: CC312Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Dose limiting toxicities (DLTs)
Toxicity will be evaluated according to the NCI CTCAE, Version 5.0, except CRS which will be graded according to ASTCT Consensus Grading for CRS.
Time frame
From the first infusion of CC312 till the end of the 28 days DLT（Dose Limiting Toxicity）observation period.2
Incidence and severity of adverse event (AE)
Overall numbers of participants with any AE, including any laboratory abnormality, treatment-emergent adverse event (TEAE), and serious adverse events (SAE). Severity (toxicity grade) for each AE will be determined using the NCI CTCAE, version 5.0; except cytokine release syndrom (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) which will be graded according to ASTCT Consensus Grading.
Time frame
From the first infusion of CC312 until 28 days following the end of treatment.Secondary outcomes
1
Pharmacokinetics (PK): serum concentration
Blood samples will be collected to analysis serum concentration of CC312. Derived PK parameters will be calculated using the non-compartmental model.
Time frame
Cycle 1: baseline (Day -10~Day -8); 1 hour-pre-dose and multiple-timepoints-post-dose; Cycle 2 and subsequent cycle: 1 hour-pre-dose; after the end of treatment (EOT)/withdraw/at the end of study (EOS). Length of each cycle: 28 days.2
Pharmacodynamics (PD): cytokine analysis
Peripheral blood will be collected for CRS-related cytokine analysis in all dose escalation cohorts.
Time frame
Cycle 1: baseline (Day -10~Day -8); 1 hour-pre-dose and multiple-timepoints-post-dose; Cycle 2 and subsequent cycle: 1 hour-pre-dose; after the end of treatment (EOT)/withdraw/at the end of study (EOS). Length of each cycle: 28 days.3
Pharmacodynamics (PD): immunophenotyping
Peripheral blood will be collected for immunophenotyping (including the activation of CD4+ and CD8+ T cells, and depletion of B cells) in all dose escalation cohorts.
Time frame
Cycle 1: baseline (Day -10~Day -8); 1 hour-pre-dose and multiple-timepoints-post-dose; Cycle 2 and subsequent cycle: 1 hour-pre-dose; after the end of treatment (EOT)/withdraw/at the end of study (EOS). Length of each cycle: 28 days.4
Immunogenicity: anti-CC312 antibody
The proportions of participants with positive anti-drug antibody (ADA) status and those with positive neutralizing anti-drug antibody (NAb) status will be presented by descriptive statistics.
Time frame
Cycle 1: baseline (Day -10~Day -8); 1 hour-pre-dose on Day-7/Day 8. Cycle 2 and subsequent cycle: within 1 hour before infusion on Day 1/Day 15; after the end of treatment (EOT)/withdraw/at the end of study (EOS). Length of each cycle: 28 days.Other outcomes
1
Tumor response to CC312
B-NHL, B-ALL and CLL will be evaluated by Lugano criteria, NCCN Guidelines 2021, and iwCLL guidelines 2008, respectively. Therapeutic endpoints includes: overall response rate \[ORR\] (including complete remission \[CR\] and partial remission \[PR\]), duration of overall response \[DOR\], disease control rate \[DCR\], and relapse-free survival \[RFS\] in participants.
Time frame
From the first infusion of CC312 until 28 days following the end of treatment.Sponsors and contacts
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Source ClinicalTrials.gov