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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by University of California, San Diego
Sponsor:
Information provided by (Responsible Party):
Thomas Kipps, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT02222688
First received: August 19, 2014
Last updated: October 24, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: cirmtuzumab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 56
Study Start Date: August 2014
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cirmtuzumab
The starting dose is 15 µg/kg. There is intra-patient dose escalation in the first 3 cohorts, followed by the standard 3+3 design for the next 5 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, the trial will switch to the standard 3+3 design without intra-patient dose escalation for all cohorts.
Drug: cirmtuzumab
Other Name: UC-961

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 UC-961 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 3 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 UC-961. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • Subjects must be aged 18 years or older.
  • Women of childbearing potential must agree not to become pregnant for the duration of the study.
  • 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 109/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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02222688

Contacts
Contact: Jesika Reiner 858-822-5364 jreiner@ucsd.edu

Locations
United States, California
UCSD Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Principal Investigator: Catriona Jamieson, MD, PhD         
Sponsors and Collaborators
Thomas Kipps
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
  More Information

Responsible Party: Thomas Kipps, Deputy Director of Research, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02222688     History of Changes
Other Study ID Numbers: #140141
Study First Received: August 19, 2014
Last Updated: October 24, 2016

Keywords provided by University of California, San Diego:
cancer
CLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell

ClinicalTrials.gov processed this record on April 28, 2017