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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: cirmtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical and phenotypic verification of B cell CLL and measurable disease. Immunophenotyping of the leukemic cells (blood or marrow) must demonstrate a monoclonal (or light chain positive) B cell population with immunophenotype consistent with CLL (e.g., co-expressing CD19 and CD5). Recovered from toxic effects attributed to UC-961 to grade 1 levels, or baseline. Must have measurable disease, including one of the following: absolute lymphocyte count greater than 5000/uL lymphadenopathy greater than 1.5 cm in longest dimension splenomegaly bone marrow biopsy with residual CLL cells, or resultant bone marrow dysfunction 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 UC-961. 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 May have had intervening therapy since completion of initial UC-961 dosing, but excluding the following: Within 7 days of UC-961 restart, or 5 half-lives (if known), whichever is shorter: small molecule tyrosine kinase inhibitor (eg: ibrutinib, idelalisib, AVL-292, IPI-145); Within 28 days of UC-961 restart: chemotherapy (e.g., purine analogues, alkylating agents), corticosteroids, radiation therapy, or participation in any other investigational drug treatment (besides UC-961); Within 56 days of UC-961 restart: previous UC-961 dosing; Within 56 days of UC-961 restart: monoclonal antibody therapy directed against CLL (e.g., rituximab, ofatumumab, obinutuzumab, alemtuzumab). Current infection requiring parenteral antibiotics. Active infection with HIV, HBV, or 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 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; Other clinically significant heart disease (e.g. uncontrolled congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cirmtuzumab<br> | Drug: cirmtuzumab<br>* cirmtuzumab, dose based on ongoing phase 1 trial, q14days x 4 doses, then q28 days x 4 doses, until disease progression.<br>* Other names: UC-961;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Adverse events assessed by CTCAE v4.0 during treatment and 3 month follow-up | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | 1 year | 
| Progression free survival |  | 1 year | 
| Stable Disease Rate (SD) |  | 1 year | 
| Partial Response Rate (PR) |  | 1 year | 
| Minimal Residual Disease Rate (MRD) |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, cancer, UC-961, cirmtuzumab