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Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

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Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Cohort 1: Cirmtuzumab 0.015 mg/kg for two 14-day cycles followed by cirmtuzumab 0.03 mg/kg for two 14-day cycles via intravenous (IV) infusion

Cohort 2: Cirmtuzumab 0.06 mg/kg for one 14-day cycle, followed by cirmtuzumab 0.12 mg/kg for one 14-day cycle, followed by 0.24 mg/kg for two 14-day cycles via IV infusion

Cohort 3: Cirmtuzumab 0.5 mg/kg for one 14-day cycle, followed by cirmtuzumab 1.0 mg/kg for three 14-day cycles via IV infusion

Cohort 4: Cirmtuzumab 2.0 mg/kg for two 14-day cycles, followed by cirmtuzumab 4.0 mg/kg for two 14-day cycles via IV infusion

Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion

Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion

Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)

cirmtuzumab

Catriona Jamieson, M.D., Ph.D.

Michael Choi, M.D.

The purpose of the study is to investigate the safety of the investigational agent, cirmtuzumab. Cirmtuzumab is a monoclonal antibody drug designed to attach to a protein, called ROR1, on the surface of chronic lymphocytic leukemia (CLL) cells to block cell growth and survival. ROR1 is rarely expressed on healthy cells so the idea is to preferentially get rid of the cancer cells. Although there is evidence in laboratory animals that cirmtuzumab can decrease the number of CLL cells, the investigators do not know if this will work in humans. This drug will be given to humans for the first time in this study. Therefore, the goal of this study is to see if cirmtuzumab is safe and tolerated in study participants.

This is a first in human, open-label single institution, Phase I dose escalation study of in patients with relapsed or refractory CLL. Treatment cycle (14 days) will consist of cirmtuzumab administered intravenously on a bi-weekly (every two weeks) schedule for a total of 4 doses. Eight dose cohorts (of 3 to 6 patients in size) plus an expansion cohort of 6 patients are planned. In the first 4 dose cohorts, there is intra-patient dose escalation to monitor for acute toxicities, such as tumor lysis syndrome.

A cycle may be repeated every 14 days if the patient has at least stable disease by clinical examination (or interim response assessment) and has again met hematologic, renal, and hepatic laboratory parameters as defined in the eligibility section, and is without ongoing Grade 3 non-hematologic or Grade 4 hematologic toxicities attributable to cirmtuzumab. The total duration of study drug administration is 4 cycles. Each cycle consists of clinical and laboratory evaluation on Day 1 and safety assessments on Days 3 and 8.

UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia

A Phase I Clinical Trial to Determine the Safety and Tolerability of UC-961 (Cirmtuzumab), an Anti-ROR1 Monoclonal Antibody, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia Who Are Ineligible for Chemotherapy

The MTD is defined as the highest dose studied at which no more than one in six patients experience a dose-limiting toxicity (DLT) during the DLT observation period. The biologically active dose will be determined at a dose below or equal to the MTD upon review of the the study data; the final determination will also consider any cumulative or delayed toxicity.

The occurrence of any of the following adverse events considered to be possibly, probably, or definitely related to cirmtuzumab within the DLT observation period (56 days from the first infusion for cohorts with intrapatient dose escalation, and 28 days of the start investigational treatment for cohorts without intrapatient dose escalation):

1. Grade 3 or greater non-hematologic toxicity with the exception of Grade 3 infusion reaction.
2. Grade 4 neutropenia lasting more than 5 days despite appropriate medical management.
3. Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement for platelets transfusion.
4. Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC).
5. Grade 4 anemia unexplained by underlying disease.
6. Any AE requiring a dose delay of greater than 14 days.
7. Patients with baseline cytopenias or starting blood counts in the grade 2 range are evaluable for hematologic DLT.

Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)

Clinical response \[stable disease (SD) or progressive disease (PD)\] defined by iwCLL criteria including clinical, hematological, and bone marrow features for a period of at least 2 months from completion of therapy

The duration of time from the start of study treatment until objective tumor progression or death

Thomas Kipps

Deputy Director of Research Operations, Moores Cancer Center

Note that some patients elected to enroll in extension study (ClinicalTrails.gov record #NCT02860676) and therefor the cut-off date for some may be the date patient was first treated on extension protocol. Timeframe for this result therefore difficult to reconcile as asked to report here.

Note no deaths observed during the timeframe of the study observation period.

Cirmtuzumab 0.015 - 0.03 mg/kg

Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg

Cirmtuzumab 0.5 - 1.0 mg/kg

Cimrtuzumab 2.0 - 4.0 mg/kg

Cirmtuzumab 8 mg/kg

Cirmtuzumab 16 mg/kg

Cirmtuzumab 20 mg/kg

Cirmtuzumab 2.0 - 4.0 mg/kg

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Twenty-seven subjects were treated with cirmtuzumab and are included in the primary outcome analysis. One subject was enrolled into the trial twice; first in Cohort 1 and then again in Cohort 4 and is counted twice for the baseline characteristics.

Some patients enrolled in extension study (#NCT02860676)\& cut-off date for AE observation may be date patient was first treated on extension, therefor AE Timeframe period difficult to reconcile. 0 deaths observed during study observation period.

Thomas Kipps, MD, PhD

All participants who received any treatment with cirmtuzumab

All Participants

Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab

Rate of Dose Limiting Toxicities (DLTs)

Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.

Stable Disease

Progressive Disease

Evaluable subjects or those who completed 4 cycles of cirmtuzumab

Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria

Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion

Progression Free Survival as Determined by iwCLL Criteria

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

Docetaxel

Tubulin Modulators

Antimitotic Agents

There is only one treatment arm on this study. The combination of cirmtuzumab + docetaxel will be administered on one treatment arm. Treatment will cirmtuzumab will be administered initially as a loading dose alone on days 1, 15, and 29 of cycle 1. Following the loading, cirmtuzumab will be given on Day 1 of every 21-day cycle starting on Cycle 2 to up to Cycle 7 corresponding with concurrent docetaxel administration. Following discontinuation or completion of docetaxel, treatment with cirmtuzumab will be continued Day 1 of every 28 cycle until disease progression, toxicity or study withdrawal. Docetaxel will be administered on day 1 of every 21-day cycle starting Cycle 2 for up to 6 cycles.

Cirmtuzumab will be given in combination with docetaxel.

Cirmtuzumab

Rana R McKay, MD

Rana McKay

The purpose of this study is to examine the safety and efficacy of cirmtuzumab in combination with standard of care docetaxel in patients with metastatic castration resistant prostate cancer. Docetaxel is a taxane chemotherapy which has been shown to prolong survival in men with castration resistant prostate cancer. Cirmtuzumab is a monoclonal antibody that targets the receptor called ROR1 of the non-canonical Wnt pathway and is suspected to contribute to prostate cancer growth and progression.

This study seeks to targeting the non-canonical Wnt pathway with an antibody against ROR1. ROR1 is an attractive target given its low expression in non-malignant tissues and its role in proliferation and survival in prostate cancer. From preclinical data in a variety of tumor types, blockade of ROR1 inhibits cell growth and cirmtuzumab has shown efficacy in clinical trials with CLL. Preclinical data suggests that ROR1 is upregulated in chemotherapy resistant cells and treatment with cirmtuzumab and a taxane achieved higher cytotoxic response than both agents alone, supporting the use of the combination of cirmtuzumab and a taxane. Based on the biological rationale behind cirmtuzumab and preclinical activity with docetaxel, this is an open label, phase 2 clinical trial to evaluate the safety and efficacy of cirmtuzumab in combination with docetaxel for the treatment of metastatic, castrate resistant prostate adenocarcinoma.

Study of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer

A Phase 1b Trial Investigating Docetaxel Combined With Cirmtuzumab in Patients With Metastatic Castration Resistant Prostate Cancer

Defined as a reduction of ≥30% from the baseline value, confirmed ≥4 weeks later.

Defined as an increase of ≥25% from baseline at ≥12 weeks, in patients with no decrease from baseline, or as an increase of ≥25% above the nadir, confirmed ≥3 weeks later, in patients with an initial decrease from baseline.

Defined by PCWG-3 criteria for bone metastases and RECIST version 1.1 for soft tissue

Time from study discontinuation to initiation of subsequent systemic anti-cancer therapy or death

Time to first symptomatic pathologic fracture, radiation to the bone given symptomatic bone metastasis, surgery to the bone given symptomatic bone metastasis, or symptomatic spinal cord compression

Time from enrollment to death or last follow up

Composite endpoint of clinical benefit defined as any one of the following: PSA response by PCWG3 criteria, objective response rate by RECIST version 1.1, and stable disease \> 6 months by RECIST version 1.1.

University of California, San Diego

Associate Professor of Medicine and Urology

Venetoclax

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.

Cycle 1, Day 1 \& 15 - 600mg Cycle 2, Day 1 to Cycle 6, Day 1 - 600mg

Venetoclax 400mg PO daily from cycle 1 day 1 for 6 cycles of 28 days.

Benjamin M Heyman, MD

Single center, open-label, phase 2 study to determine the efficacy of cirmtuzumab consolidation in patients with measurable disease on venetoclax.

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.

Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax

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.

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

Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.

Measurement of time of anti-cancer activity

Oncternal Therapeutics, Inc

Assistant Clinical Professor

cirmtuzumab, dose based on ongoing phase 1 trial, q14days x 4 doses, then q28 days x 4 doses, until disease progression.

Catriona Jamieson, MD, PhD

Michael Y Choi, MD

The purpose of the study is to investigate the safety of the investigational drug called cirmtuzumab when given for a duration of 6 to 12 months. Cirmtuzumab is a type of drug called a monoclonal antibody. This drug is designed to attach to a protein called ROR1 that is on the surface of chronic lymphocytic leukemia (CLL) cells. This blocks growth and survival of the CLL cells. ROR1 is rarely expressed on healthy cells so this drug should target the cancer cells. Cirmtuzumab is considered experimental because its use is not approved by United States (US) Food and Drug Administration (FDA).

Although there is evidence from tests on laboratory animals that cirmtuzumab can decrease the number of CLL cells, the investigators do not know if this will work in humans. Therefore, the goal of this study is to see if cirmtuzumab is safe and tolerable in study participants when given for a duration of 6 to 12 months.

This is an open-label extension study to determine the safety and tolerability of cirmtuzumab given to participants who enrolled and completed the initial phase 1 trial in CLL without a dose-limiting toxicity.

UC-961 is administered by intravenous infusion every 14 days for 4 doses, then every 28 days for 4 doses, after which responses will be assessed. Patients with an objective response (meeting working group criteria for partial response or complete response) will continue at the same dose and schema. Patients with stable disease or progressive disease are eligible to increase the dose of UC-961 for another 6-month course.

Duration of UC-961 administration is until disease progression, treatment intolerance, or lack of clinical benefit.

Extension Study of UC-961 (Cirmtuzumab) for Patients With Chronic Lymphocytic Leukemia Treated Previously With UC-961

A Phase 1 Extension Study to Determine the Safety of UC-961 (Cirmtuzumab) at the Recommended Phase 2 Dose for Retreatment of Patients With Chronic Lymphocytic Leukemia Treated Previously With UC-961

Adverse events assessed by CTCAE v4.0 during treatment and 3 month follow-up

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia	NCT02222688	Chronic Lymphoc...	cirmtuzumab	18 Years - 70 Years	University of California, San Diego
Study of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer	NCT05156905	Metastatic Cast...	Cirmtuzumab	18 Years -	University of California, San Diego
Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax	NCT04501939	Chronic Lymphoc...	Cirmtuzumab Venetoclax	18 Years -	University of California, San Diego
Cirmtuzumab Consolidation for Treatment of Patients With Detectable CLL on Venetoclax	NCT04501939	Chronic Lymphoc...	Cirmtuzumab Venetoclax	18 Years -	University of California, San Diego
Extension Study of UC-961 (Cirmtuzumab) for Patients With Chronic Lymphocytic Leukemia Treated Previously With UC-961	NCT02860676	Chronic Lymphoc...	cirmtuzumab	18 Years -	University of California, San Diego
Study of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer	NCT05156905	Metastatic Cast...	Cirmtuzumab	18 Years -	University of California, San Diego

Spots Global Cancer Trial Database for cirmtuzumab

Every month we try and update this database with for cirmtuzumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cirmtuzumab

Every month we try and update this database with for cirmtuzumab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cirmtuzumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.