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Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax (Venetoclax)

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cirmtuzumab
Venetoclax
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring chronic lymphocytic leukemia, CLL, cirmtuzumab, venetoclax

Eligibility Criteria

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

Inclusion Criteria:

  • Must have detectable CLL/SLL (> 0.01% leukemia cells present)
  • Must have received at least 12 months of venetoclax.
  • Patients may be receiving venetoclax at the time of screening and study entry.
  • Patients who have discontinued venetoclax more than 6 months prior to study entry must still have a disease burden meeting criteria for low risk of TLS (i.e. no lymph node greater than 5 cm in diameter; absolute lymphocyte count less than 25 k/uL)

Exclusion Criteria:

Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

  • Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
  • Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
  • Child class B or C cirrhosis

Treatment with any of the following within 7 days prior to the first dose of cirmtuzumab:

  • Steroid therapy for anti-neoplastic intent
  • Biologic agent (monoclonal antibody) within 30 days for anti-neoplastic intent.
  • Chemotherapy (purine analog or alkylating agent) or target small molecule agent within 14 days or 5 half-lives (whichever is shorter), or has not recovered to less than CTCAE grade 2 clinically significant adverse effect(s)/toxicity(s) of previous therapy.
  • CLL therapy, aside from venetoclax.
  • History of other malignancy that could affect compliance with the protocol or interpretation of results (example: patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible.)
  • Women who are pregnant or lactating

Sites / Locations

  • UCSD Koman Family Outpatient PavilionRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cirmtuzumab + Venetoclax

Arm Description

All patients will receive a minimum of 6 cycles (cycle = 28 days) of therapy with venetoclax and cirmtuzumab during the treatment period. For patients who achieve undetectable minimal residual disease (uMRD) positive after cycle 6, an additional 6 cycles of venetoclax and cirmtuzumab may be administered.

Outcomes

Primary Outcome Measures

Cancer response to treatment
Percentage of subjects with undetectable measurable residual disease after 6 months of cirmtuzumab + venetoclax treatment.

Secondary Outcome Measures

Frequency of adverse events
Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
Time to next CLL treatment.
Measurement of time of anti-cancer activity

Full Information

First Posted
July 22, 2020
Last Updated
February 28, 2023
Sponsor
University of California, San Diego
Collaborators
Oncternal Therapeutics, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT04501939
Brief Title
Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax
Acronym
Venetoclax
Official Title
Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 6, 2020 (Actual)
Primary Completion Date
July 22, 2025 (Anticipated)
Study Completion Date
July 22, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
Oncternal Therapeutics, Inc

4. Oversight

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

5. Study Description

Brief Summary
Single center, open-label, phase 2 study to determine the efficacy of cirmtuzumab consolidation in patients with measurable disease on venetoclax.
Detailed Description
This is a phase 2 study to test whether cirmtuzumab in combination with venetoclax given as consolidation therapy can decrease the number of cancer cells that may be left in the bone marrow or in the blood in patients who have been treated with venetoclax for at least one year. Consolidation therapy is given after initial cancer treatment to further reduce the number of cancer cells that may be left in the body. Cirmtuzumab, a monoclonal antibody that inhibits receptor tyrosine kinase like orphan receptor (ROR1) signaling and stemness, may be effective in reducing the risk of disease progression in patients with detectable minimal residual disease (MRD) after treatment with venetoclax.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
chronic lymphocytic leukemia, CLL, cirmtuzumab, venetoclax

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cirmtuzumab + Venetoclax
Arm Type
Experimental
Arm Description
All patients will receive a minimum of 6 cycles (cycle = 28 days) of therapy with venetoclax and cirmtuzumab during the treatment period. For patients who achieve undetectable minimal residual disease (uMRD) positive after cycle 6, an additional 6 cycles of venetoclax and cirmtuzumab may be administered.
Intervention Type
Drug
Intervention Name(s)
Cirmtuzumab
Other Intervention Name(s)
Zilovertamab
Intervention Description
Cycle 1, Day 1 & 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
VENCLEXTA
Intervention Description
Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.
Primary Outcome Measure Information:
Title
Cancer response to treatment
Description
Percentage of subjects with undetectable measurable residual disease after 6 months of cirmtuzumab + venetoclax treatment.
Time Frame
6-24 months
Secondary Outcome Measure Information:
Title
Frequency of adverse events
Description
Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
Time Frame
9-15 months
Title
Time to next CLL treatment.
Description
Measurement of time of anti-cancer activity
Time Frame
9-24 months
Other Pre-specified Outcome Measures:
Title
Change in gene expression in leukemic cells
Description
The change in gene expression of leukemia cells by single cell PCR or RNA after treatment with cirmtuzumab, including analysis of archival pre-venetoclax sample, when available.
Time Frame
9-15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have detectable CLL/SLL (> 0.01% leukemia cells present) Must have received at least 12 months of venetoclax. Patients may be receiving venetoclax at the time of screening and study entry. Patients who have discontinued venetoclax more than 6 months prior to study entry must still have a disease burden meeting criteria for low risk of TLS (i.e. no lymph node greater than 5 cm in diameter; absolute lymphocyte count less than 25 k/uL) Exclusion Criteria: Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: Uncontrolled and/or active systemic infection (viral, bacterial or fungal) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate. Child class B or C cirrhosis Treatment with any of the following within 7 days prior to the first dose of cirmtuzumab: Steroid therapy for anti-neoplastic intent Biologic agent (monoclonal antibody) within 30 days for anti-neoplastic intent. Chemotherapy (purine analog or alkylating agent) or target small molecule agent within 14 days or 5 half-lives (whichever is shorter), or has not recovered to less than CTCAE grade 2 clinically significant adverse effect(s)/toxicity(s) of previous therapy. CLL therapy, aside from venetoclax. History of other malignancy that could affect compliance with the protocol or interpretation of results (example: patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible.) Women who are pregnant or lactating
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Benjamin Heyman, MD
Phone
(858) 246-3038
Email
bheyman@health.ucsd.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Betty Cabrera, MPH
Phone
858-534-5932
Email
blcabrera@health.ucsd.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin M Heyman, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSD Koman Family Outpatient Pavilion
City
San Diego
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Miller
Phone
858-249-3000
Email
eamiller@ucsd.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34398557
Citation
Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.
Results Reference
derived

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Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax

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