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

Conditions

Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma, Small Lymphocytic Lymphoma

Keywords

Oral, DLBCL, PMBCL, BCLU, GZL, MCL, FL, MZL, WM, LPL, CLL, SLL

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.

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Blood2020-11-048 citations

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Abstract 4225: CG-806, a first-in-class FLT3/BTK inhibitor, and venetoclax synergize to inhibit cell proliferation and to induce apoptosis in aggressive B-cell lymphomas

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Abstract CT239: Early clinical findings from a phase 1a/b dose escalation trial to evaluate the safety and tolerability of CG-806 in patients with relapsed or refractory CLL/SLL or non-Hodgkin's lymphomas

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Cancer Research2020-08-151 citations

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A Phase 1 a/b Dose Escalation Trial to Evaluate the Safety and Tolerability of CG-806 in Patients with Relapsed or Refractory CLL/SLL or Non-Hodgkin's Lymphomas

Stephen B. Howell, Hongying Zhang, William G. Rice

Blood2019-11-133 citations

10.1182/blood-2019-130784

Interventions

DRUGCG-806

CG-806 will be given orally in ascending doses starting at 150 mg PO BID until the maximum tolerated dose or recommended dose is reached.

Study design

Allocation

NA

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Incidence of treatment-emergent adverse events of CG-806	Cycle 1 (28 days)	To determine the safety and tolerability of CG-806.
Establish a CG-806 dose that maintains a biologically active plasma concentration	Cycle 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-806	Up 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.

Secondary

Measure	Time frame	Description
Pharmacokinetic variables including volume of distribution	Cycle 1 (28 days)	Pharmacokinetic variables including volume of distribution
Pharmacokinetic variables including clearance	Cycle 1 (28 days)	Pharmacokinetic variables including clearance
Pharmacokinetic variables including serum half-life	Cycle 1 (28 days)	Pharmacokinetic variables including serum half-life
To assess the antitumor activity of CG-806 using FDG PET-CT imaging evaluations	Average 2 Cycles (8 weeks)	To assess the antitumor activity of CG-806 using FDG PET-CT imaging evaluations
Pharmacokinetic variables including maximum plasma concentration (Cmax)	Cycle 1 (28 days)	Pharmacokinetic variables including maximum plasma concentration (Cmax)
Pharmacodynamic biomarkers of drug effect including selected mRNA levels	Average 2 cycles (8 weeks)	Pharmacodynamic biomarkers of drug effect including selected mRNA levels
To assess the relative BA of formulation G1 against formulation G2	Cycle 1 (28 days)	To assess the relative bioavailability of original formulation (G1) against new generation formulation (G2).
To assess the relative BA of formulation G1 against formulation G3	Cycle 1 Lead-Up (3 days)	To assess the relative bioavailability of original formulation (G1) against new generation formulation (G3).
Pharmacodynamic biomarkers of drug effect including BTK activity	Average 2 cycles (8 weeks)	Pharmacodynamic biomarkers of drug effect including BTK activity
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 (AUC	Cycle 1 (28 days)	Pharmacokinetic variables including Area Under the Curve (AUC)

Countries

United States

Outcome results

None listed