Sepantronium Bromide for the Treatment of High-grade B-cell Lymphoma

Study Overview
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Brief Summary
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This is a multi-center Phase 2 study to determine the safety and efficacy of sepantronium bromide (SepB) in adult patients with relapsed or refractory high-grade B-cell lymphoma

Detailed Description
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This is a multi-center, open label, dose-ranging Phase 2 study evaluating the safety and efficacy of SepB in patients with relapsed/refractory c-Myc rearranged HGBCL. Cohorts of three patients will be enrolled at each dose level for SepB with expansion to six patients, if necessary, to assess toxicity. Following the completion of 2 cycles of treatment of each cohort, an independent Data Monitoring Committee (DMC) will review the safety data to assess study drug related toxicities from the current cohort. Following this review, a decision will be made to continue dose escalation to the next dose level, to declare that a given dose level is the level of dose-limiting toxicity (DLT) or to further explore toxicity at the dose level in question by enrolling additional subjects to a maximum of six subjects at that level. An additional 6 patients will be enrolled at the recommended Phase 2 dose (RP2D). The RP2D will be established on the basis of the maximally tolerated dose between the two specified dose levels as well as other relevant data, including clinical signals of activity, pharmacokinetic (PK) and pharmacodynamic (PD) data.

Official Title
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A Phase 2, Multicenter, Open Label Dose-ranging Study of Sepantronium Bromide in Patients With Relapsed/Refractory c-Myc Rearranged High-grade B-cell Lymphoma (HGBCL)

Conditions
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High-grade B-cell Lymphoma, Burkitt Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphatic Diseases, Lymphoma, High-Grade, C-MYC/BCL2 Double-Hit High-Grade B-Cell Lymphoma, C-MYC/BCL6 Double-Hit High-Grade B-Cell Lymphoma, C-Myc Gene Rearrangement

Intervention / Treatment
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* Drug: Sepantronium Bromide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed histologic diagnosis of c-Myc rearranged high-grade B-cell lymphoma Relapse or refractory disease after at least one previous line of therapy Measurable disease as defined by 2014 Lugano classification ECOG performance status of 0-2 Acceptable coagulation parameters Exclusion Criteria: Allogeneic transplant within 3 months Autologous transplant without resolution of post-transplant cytopenias Known CNS involvement Average QT/QTc interval duration > 450 msec Inadequate marrow, hepatic or renal function Unresolved Grade 2 or greater toxicities from prior anticancer therapy Radiotherapy within prior 4 weeks Requires systemic immunosuppressive therapy Positive for Hepatis B or Hepatis C Seropositive for HIV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose range findings study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1 will receive a dose of 3.6 mg/m2/day of sepantronium bromide | Drug: Sepantronium Bromide<br>* continuous intravenous infusion<br>* Other names: PC-002;|
| Experimental: Cohort 2<br>Cohort 1 will receive a dose of 4.8 mg/m2/day of sepantronium bromide | Drug: Sepantronium Bromide<br>* continuous intravenous infusion<br>* Other names: PC-002;|
| Experimental: Recommended Phase 2 Dose - Cohort 3<br>The recommended Phase 2 dose will be established based on the safety, pharmacokinetic and pharmacodynamic data from Cohort 1 and Cohort 2 | Drug: Sepantronium Bromide<br>* continuous intravenous infusion<br>* Other names: PC-002;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability and recommended Phase 2 dose of sepantronium bromide | Frequency, severity and relatedness of adverse events and the frequency of adverse events requiring discontinuation of study drug or dose reductions | From time of signing informed consent through 30 days after the last dose of study drug, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | The ORR is defined as the percentage of participants who achieve either a Partial Response or Complete Response at any time during the treatment phase | From first dose through the last dose of study drug, an average of 6 months | 
| Complete response rate | Percentage of patients who experience a confirmed Complete Response at any time during the treatment phase | From first dose of study drug through the last dose of study drug, an average of 6 months | 
| Duration of response | Time from the first documentation of a Complete Response or a Partial Response until the time to objective tumor progression | From first dose of study drug through to time of progression, an average of 6 months | 
| Clinical benefit rate | Proportion of patients who achieve a Complete Response, Partial Response or Stable Disease during the treatment phase | From first dose of study drug through the last dose of study drug, an average of 6 months | 
| Overall survival | The time from the first dose of study drug until death from any cause or date of last follow-up for living and lost to follow-up patients | From first dose of study drug through date of death, irrespective of cause, an average of 6 months | 
| Progression Free Survival | The time from first dose until relapse, disease progression or death due to any cause | From first dose of study drug through relapse, disease progression or death due to any cause, an average of 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed/refractory