search
Back to results

CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory CLL

Primary Purpose

Relapsed or Refractory Chronic Lymphocytic Leukemia

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CYC065
Venetoclax
Sponsored by
Cyclacel Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed or Refractory Chronic Lymphocytic Leukemia focused on measuring CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, chronic lymphocytic leukemia, small lymphocytic lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • CLL that is relapsed or refractory to BTK inhibitors and is on a stable dose of venetoclax
  • ECOG 0-2
  • Adequate bone marrow function
  • Adequate renal function
  • Adequate liver function
  • INR <=1.2 in patients not receiving chronic anticoagulation
  • At least 4 weeks from prior cytotoxic chemotherapy
  • At least 4 weeks from major surgery
  • Agree to practice effective contraception

Exclusion Criteria:

  • Known CLL involvement in CNS that is symptomatic and active
  • currently receiving radiotherapy, biological therapy, or any other investigational agents
  • Uncontrolled intercurrent illness
  • Pregnant or lactating
  • Known to be HIV-positive
  • Known active hepatitis B and/or hepatitis C infection

Sites / Locations

  • Investigational Site
  • Investigational Site
  • Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CYC065 and venetoclax

Arm Description

CYC065 will be administered intravenously via 4-hour infusion on Day 1 and Day 15 after the venetoclax ramp-up schedule is completed. Venetoclax will be taken daily at a dose that is deemed safe and tolerable after the ramp-up schedule. One cycle will be 28 days or 4 weeks.

Outcomes

Primary Outcome Measures

Number of patients who experience dose-limiting toxicity (DLT)

Secondary Outcome Measures

Pharmacokinetic effect
Plasma drug level
Pharmacodynamic effect
MCL-1 level in peripheral white blood cells

Full Information

First Posted
October 1, 2018
Last Updated
April 22, 2022
Sponsor
Cyclacel Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT03739554
Brief Title
CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory CLL
Official Title
A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 25, 2019 (Actual)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cyclacel Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A Phase I Combination Study of CYC065 and Venetoclax for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Detailed Description
This is an open-label, single arm, dose escalation study in patients with relapsed or refractory CLL. Treatment will be administered on an outpatient basis and all patients will receive CYC065 over 4-hour infusion once every 2 weeks on Day 1 and Day 15 in combination with venetoclax. One treatment cycle is 4 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Chronic Lymphocytic Leukemia
Keywords
CYC065, CDK2/9, venetoclax, BCL-2, MCL-1, Relapsed, Refractory, chronic lymphocytic leukemia, small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Three to 6 patients will be entered at a given CYC065 dose level. Dose escalation will be 33% until one out of 3 patients experienced a DLT at a given dose level. Dose escalation will continue at 25% if no additional DLT is observed; otherwise, dose escalation will be stopped. At least 6 patients will be treated at RD.
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CYC065 and venetoclax
Arm Type
Experimental
Arm Description
CYC065 will be administered intravenously via 4-hour infusion on Day 1 and Day 15 after the venetoclax ramp-up schedule is completed. Venetoclax will be taken daily at a dose that is deemed safe and tolerable after the ramp-up schedule. One cycle will be 28 days or 4 weeks.
Intervention Type
Drug
Intervention Name(s)
CYC065
Intervention Description
intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199
Intervention Description
oral capsule
Primary Outcome Measure Information:
Title
Number of patients who experience dose-limiting toxicity (DLT)
Time Frame
At the end of cycle 1 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Pharmacokinetic effect
Description
Plasma drug level
Time Frame
At the end of cycle 1 (each cycle is 28 days)
Title
Pharmacodynamic effect
Description
MCL-1 level in peripheral white blood cells
Time Frame
At the end of cycle 1 (each cycle is 28 days)
Other Pre-specified Outcome Measures:
Title
Anti-tumor activity
Description
Response assessed by investigators based on International Workshop for CLL criteria or International Working Group criteria for patients with small lymphocytic lymphoma.
Time Frame
From the date of first dose of CYC065 to 4 weeks after the last dose of CYC065

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: CLL that is relapsed or refractory to BTK inhibitors and is on a stable dose of venetoclax ECOG 0-2 Adequate bone marrow function Adequate renal function Adequate liver function INR <=1.2 in patients not receiving chronic anticoagulation At least 4 weeks from prior cytotoxic chemotherapy At least 4 weeks from major surgery Agree to practice effective contraception Exclusion Criteria: Known CLL involvement in CNS that is symptomatic and active currently receiving radiotherapy, biological therapy, or any other investigational agents Uncontrolled intercurrent illness Pregnant or lactating Known to be HIV-positive Known active hepatitis B and/or hepatitis C infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Kirschbaum, MD
Organizational Affiliation
Cyclacel Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Investigational Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

CYC065 CDK Inhibitor and Venetoclax Study in Relapsed/Refractory CLL

We'll reach out to this number within 24 hrs