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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

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

NCT ID

NCT04501939

First Posted

July 22, 2020

Last Updated

February 28, 2023

Sponsor

University of California, San Diego

Collaborators

Oncternal Therapeutics, Inc

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

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

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

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

bheyman@health.ucsd.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Betty Cabrera, MPH

Phone

858-534-5932

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

eamiller@ucsd.edu

12. IPD Sharing Statement

Plan to Share IPD

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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