Burkitt Lymphoma, C-MYC/BCL2 Double-Hit High-Grade B-Cell Lymphoma, C-MYC/BCL6 Double-Hit High-Grade B-Cell Lymphoma, C-Myc Gene Rearrangement, High-grade B-cell Lymphoma, Lymphatic Diseases, Lymphoma, B-Cell, Lymphoma, High-Grade, Lymphoma, Large B-Cell, Diffuse
Conditions
Keywords
Relapsed/refractory
Brief summary
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
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.
Interventions
DRUGSepantronium Bromide
continuous intravenous infusion
Sponsors
Cothera Bioscience, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose range findings study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability and recommended Phase 2 dose of sepantronium bromide | From time of signing informed consent through 30 days after the last dose of study drug, an average of 6 months | Frequency, severity and relatedness of adverse events and the frequency of adverse events requiring discontinuation of study drug or dose reductions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | From first dose of study drug through the last dose of study drug, an average of 6 months | Percentage of patients who experience a confirmed Complete Response at any time during the treatment phase |
| Duration of response | From first dose of study drug through to time of progression, an average of 6 months | Time from the first documentation of a Complete Response or a Partial Response until the time to objective tumor progression |
| Overall response rate | From first dose through the last dose of study drug, an average of 6 months | 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 |
| Overall survival | From first dose of study drug through date of death, irrespective of cause, an average of 6 months | 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 |
| Progression Free Survival | From first dose of study drug through relapse, disease progression or death due to any cause, an average of 12 months | The time from first dose until relapse, disease progression or death due to any cause |
| Clinical benefit rate | From first dose of study drug through the last dose of study drug, an average of 6 months | Proportion of patients who achieve a Complete Response, Partial Response or Stable Disease during the treatment phase |
Countries
China, South Korea
Outcome results
None listed