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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02222688
Recruitment Status : Completed
First Posted : August 21, 2014
Last Update Posted : March 27, 2019
Sponsor:
Information provided by (Responsible Party):
Thomas Kipps, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE August 19, 2014
First Posted Date  ICMJE August 21, 2014
Last Update Posted Date March 27, 2019
Actual Study Start Date  ICMJE August 8, 2014
Actual Primary Completion Date October 10, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2019)
  • Determine the maximum tolerated dose (MTD) or biologically active dose of Cirmtuzumab [ Time Frame: 1 year ]
    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.
  • Determine the 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2014)
  • Determine the maximum tolerated dose (MDT) or biologically active dose of Cirmtuzumab [ Time Frame: 1 year ]
    The MDT is defined as the highest dose studied at which no more than one in six patients experience a DLT.
  • Determine the rate of dose limiting toxicities (DLTs) [ Time Frame: within 56 days of starting study treatment ]
Change History Complete list of historical versions of study NCT02222688 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: cirmtuzumab
Other Name: UC-961
Study Arms  ICMJE Experimental: cirmtuzumab
The starting dose is 15 µg/kg. There is intra-patient dose escalation in the first 4 cohorts, followed by the standard 3+3 design for the subsequent cohorts until a maximum tolerated dose (MTD) or biologically active dose is reached. If there is a grade ≥ 2 adverse event in the cohorts with intra-patient dose escalation, then the dose escalation scheme will switch to a standard 3+3 dose-escalation design without intra-patient dose escalation.
Intervention: Drug: cirmtuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 25, 2019)
26
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2014)
56
Actual Study Completion Date  ICMJE May 1, 2018
Actual Primary Completion Date October 10, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02222688
Other Study ID Numbers  ICMJE #140141
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Kipps, University of California, San Diego
Study Sponsor  ICMJE Thomas Kipps
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Catriona Jamieson, M.D., Ph.D. University of California Medical Center
Principal Investigator: Michael Choi, M.D. University of Calilfornia Medical Center
PRS Account University of California, San Diego
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP