Clinical Trials /

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

NCT02222688

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">UC-961</span> (<span class="go-doc-concept go-doc-intervention">Cirmtuzumab</span>) in Relapsed or Refractory <span class="go-doc-concept go-doc-disease">Chronic Lymphocytic Leukemia</span>

Title

  • Brief Title: UC-961 (Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia
  • 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
  • Clinical Trial IDs

    NCT ID: NCT02222688

    ORG ID: #140141

    Trial Conditions

    Chronic Lymphocytic Leukemia

    Trial Interventions

    Drug Synonyms Arms
    cirmtuzumab UC-961 cirmtuzumab

    Trial 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.

    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.

    Trial Arms

    Name Type Description Interventions
    cirmtuzumab Experimental The starting dose is 15 g/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. cirmtuzumab

    Eligibility 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 70 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Determine the maximum tolerated dose (MDT) or biologically active dose of Cirmtuzumab

    Determine the rate of dose limiting toxicities (DLTs)

    Secondary Outcome Measures

    Trial Keywords

    cancer

    CLL