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A Study of CG-806 in Patients With Relapsed or Refractory CLL/SLL or Non-Hodgkin's Lymphomas

Phase 1
Terminated
Conditions
Chronic Lymphocytic Leukemia
Non-Hodgkin's Lymphoma
Small Lymphocytic Lymphoma
Interventions
Registration Number
NCT03893682
Lead Sponsor
Aptose Biosciences Inc.
Brief Summary

This study is being done to evaluate the safety, tolerability and effectiveness of Oral CG-806 for the treatment of patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or Non-Hodgkin's Lymphomas who have failed or are intolerant to two or more lines of established therapy or for whom no other treatment options are available.

Detailed Description

This is a multicenter, open-label, Phase Ia/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory CLL/SLL or Non-Hodgkin's Lymphoma patients. This is to be followed by a cohort expansion phase at the MTD or recommended oral dose.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
36
Inclusion Criteria
  • Age ≥ 18 years
  • Life expectancy of at least 2 months
  • ECOG Performance Status ≤ 2
  • Patients must be able to swallow capsules
  • Adequate hematologic parameters, unless cytopenias are disease caused
  • Adequate renal, liver and cardiac function parameters
Exclusion Criteria
  • Patients with GVHD requiring systemic immunosuppressive therapy
  • Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinical significant disease related metabolic disorder
  • Clinically significant intravascular coagulation
  • Treatment with other investigational drugs within 14 days prior to first study treatment administration

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose Escalation and ExpansionCG-806CG-806 will be given orally in ascending doses in patients with relapsed or refractory CLL/SLL or Non-Hodgkin's Lymphomas (escalation cohort), until the maximum tolerated dose or recommended dose is reached. Followed by up to 100 patients enrolled in the expansion cohort at the recommended dose.
Primary Outcome Measures
NameTimeMethod
Establish a CG-806 dose that maintains a biologically active plasma concentrationCycle 1 (28 days)

To determine the dose of CG-806 given orally every 12 hours that maintains a biologically active plasma concentration over a period of 28 days.

Establish recommended dose for future development of CG-806Up to 10 months

To establish the recommended Phase 2 dose (RP2D) of CG-806 for future clinical trials in patients with advanced CLL/SLL or NHL.

Incidence of treatment-emergent adverse events of CG-806Cycle 1 (28 days)

To determine the safety and tolerability of CG-806.

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetic variables including maximum plasma concentration (Cmax)Cycle 1 (28 days)

Pharmacokinetic variables including maximum plasma concentration (Cmax)

Pharmacokinetic variables including minimum plasma concentration (Cmin)Cycle 1 (28 days)

Pharmacokinetic variables including minimum plasma concentration (Cmin)

Pharmacokinetic variables including Area Under the Curve (AUC) Pharmacokinetic variables including Area Under the Curve (AUC Pharmacokinetic variables including Area Under the Curve (AUCCycle 1 (28 days)

Pharmacokinetic variables including Area Under the Curve (AUC)

To assess the relative BA of formulation G1 against formulation G3Cycle 1 Lead-Up (3 days)

To assess the relative bioavailability of original formulation (G1) against new generation formulation (G3).

To assess the antitumor activity of CG-806 using FDG PET-CT imaging evaluationsAverage 2 Cycles (8 weeks)

To assess the antitumor activity of CG-806 using FDG PET-CT imaging evaluations

Pharmacodynamic biomarkers of drug effect including selected mRNA levelsAverage 2 cycles (8 weeks)

Pharmacodynamic biomarkers of drug effect including selected mRNA levels

Pharmacokinetic variables including volume of distributionCycle 1 (28 days)

Pharmacokinetic variables including volume of distribution

Pharmacokinetic variables including serum half-lifeCycle 1 (28 days)

Pharmacokinetic variables including serum half-life

Pharmacokinetic variables including clearanceCycle 1 (28 days)

Pharmacokinetic variables including clearance

Pharmacodynamic biomarkers of drug effect including BTK activityAverage 2 cycles (8 weeks)

Pharmacodynamic biomarkers of drug effect including BTK activity

To assess the relative BA of formulation G1 against formulation G2Cycle 1 (28 days)

To assess the relative bioavailability of original formulation (G1) against new generation formulation (G2).

Trial Locations

Locations (30)

University of California Los Angeles

🇺🇸

Los Angeles, California, United States

Pacific Cancer Care

🇺🇸

Monterey, California, United States

Torrance Memorial Physician Network

🇺🇸

Redondo Beach, California, United States

UCSD Moores Cancer Center

🇺🇸

San Diego, California, United States

Sharp Clinical Oncology Research

🇺🇸

San Diego, California, United States

Ridley-Tree Cancer Center

🇺🇸

Santa Barbara, California, United States

St. Joseph Heritage Heathcare

🇺🇸

Santa Rosa, California, United States

Rocky Mountain Cancer Centers

🇺🇸

Aurora, Colorado, United States

Mayo Clinic Jacksonville

🇺🇸

Jacksonville, Florida, United States

Orlando Health

🇺🇸

Orlando, Florida, United States

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University of California Los Angeles
🇺🇸Los Angeles, California, United States
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