- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02222688
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
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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La Jolla, California, United States, 92093
- UCSD Moores Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA:
- Clinical and phenotypic verification of B cell CLL and measurable disease. Immunophenotyping of the leukemic cells must demonstrate a monoclonal B cell population with immunophenotype consistent with CLL.
- Relapsed or refractory disease, defined by failure to achieve a partial response within 6 months of initiation of therapy, or a 50% increase of baseline disease measurements after achieving a clinical response.
- Not amenable to approved therapies.
Prior Therapy: Must have progressed after purine-analog or alkylator based therapy, or be considered inappropriate for chemo-immunotherapy due to one of the following:
- Del 17p, which is associated with poor response to chemo-immunotherapy, or
- Age greater than 70, or
- Age greater than 65 with one of the following:
- Grade ≥ 3 neutropenia, anemia, or thrombocytopenia attributable to cumulative myelotoxicity from prior administration of cytotoxic agents (as documented by bone marrow biopsy obtained since last prior therapy), or
- Clinically apparent autoimmune cytopenia which may be exacerbated by fludarabine therapy, or
- Estimated creatinine clearance (eCCr) <70 mL/min (as determined by the Cockcroft-Gault method), or
- Eastern Cooperative Oncology Group (ECOG) performance status greater than 0.
- Has recovered from the toxic effects of prior therapy to their clinical baseline.
- Women of childbearing potential must agree not to become pregnant for the duration of the study. Both men and women must agree to use a barrier method of contraception for the duration of the study and until 10 weeks after the final dose of cirmtuzumab.
Subjects must have at least one of the following indications for treatment:
- Symptomatic or progressive splenomegaly;
- Symptomatic lymph nodes, nodal clusters, or progressive lymphadenopathy;
- Progressive anemia (hemoglobin ≤ 11 g/dL);
- Progressive thrombocytopenia (platelets ≤ 100 x 10^9/L);
- Weight loss > 10% body weight over the preceding 6 month period;
- Fatigue attributable to CLL;
- Fever or night sweats for > 2 weeks without evidence of infection;
- Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of less than 12 months.
- Subjects must have an ECOG performance status of 0-2.
- Adequate hematologic function
- Adequate renal function
- Adequate hepatic function
- Adequate coagulation tests
EXCLUSION CRITERIA:
- Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
- Patients who are currently receiving another investigational agent are excluded.
- Patients who have had chemotherapy (e.g., purine analogues, alkylating agents), immunotherapy, radiation therapy, or participation in any investigational drug treatment within 4 weeks of initiation of UC-961 or at any time during the study.
- Patients who have had prior (within 8 weeks of initiation of UC-961) or concurrent antibody therapy directed against CLL (i.e., Rituxan® and Campath®).
- Current infection requiring parenteral antibiotics.
- Active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).
- Concurrent malignancy or prior malignancy within the previous 3 years (other than completely resected carcinoma in situ, prostate cancer, or localized non-melanoma skin cancer).
- Known central nervous system (CNS) involvement by malignancy.
- Untreated autoimmunity such as autoimmune hemolytic anemia, or immune thrombocytopenia.
- Uncompensated hypothyroidism (defined as thyroid-stimulating hormone (TSH) greater than 2x upper limit of normal not treated with replacement hormone).
- Presence of more than 55% pro-lymphocytes in peripheral blood. Patients with Richter's transformation are not excluded.
- Insufficient recovery from surgical-related trauma or wound healing.
Impaired cardiac function including any of the following:
- Myocardial infarction within 6 months of starting study drug;
- A past medical history of clinically significant ECG abnormalities, including QTc 481 milliseconds or greater;
- Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SEQUENTIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Cirmtuzumab 0.015 - 0.03 mg/kg
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
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Other Names:
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EXPERIMENTAL: Cirmtuzumab 0.06 - 0.12 - 0.24 mg/kg
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
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Other Names:
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EXPERIMENTAL: Cirmtuzumab 0.5 - 1.0 mg/kg
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
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Other Names:
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EXPERIMENTAL: Cirmtuzumab 2.0 - 4.0 mg/kg
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
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Other Names:
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EXPERIMENTAL: Cirmtuzumab 8 mg/kg
Cohort 5: Cirmtuzumab 8 mg/kg for four 14-day cycles via IV infusion
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Other Names:
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EXPERIMENTAL: Cirmtuzumab 16 mg/kg
Cohort 6: Cirmtuzumab 16 mg/kg for four 14-day cycles (or maximum 2000 mg) via IV infusion
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Other Names:
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EXPERIMENTAL: Cirmtuzumab 20 mg/kg
Cohort 7: Cirmtuzumab 20 mg/kg for four 14-day cycles (or maximum 2000 mg)
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) or Biologically Active Dose of Cirmtuzumab
Time Frame: 1 year
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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.
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1 year
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Rate of Dose Limiting Toxicities (DLTs)
Time Frame: The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts
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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):
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The DLT observation period is 56 days from the start of the first infusion for the intra-patient dosing cohorts and 28 days after the start of the first infusion for subsequent dosing cohorts
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability of UC-961 by Ongoing Evaluation of AEs.
Time Frame: From the start of investigational treatment to completion of follow-up, an average of 33 weeks
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Treatment emergent adverse events (description, timing, CTCAE grade, severity, seriousness, and relatedness)
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From the start of investigational treatment to completion of follow-up, an average of 33 weeks
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Clinical Activity Determined by the International Working Group in CLL (iwCLL) Criteria
Time Frame: From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days
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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
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From baseline visit to response assessment visit at 56 days after final cirmtuzumab infusion, an average of 52 days
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Progression Free Survival as Determined by iwCLL Criteria
Time Frame: From start of treatment until objective tumor progression or death
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The duration of time from the start of study treatment until objective tumor progression or death
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From start of treatment until objective tumor progression or death
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Catriona Jamieson, M.D., Ph.D., University of California Medical Center
- Principal Investigator: Michael Choi, M.D., University of Calilfornia Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- #140141
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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