Status:

COMPLETED

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

Lead Sponsor:

Thomas Kipps

Conditions:

Chronic Lymphocytic Leukemia

Eligibility:

All Genders

18-70 years

Phase:

PHASE1

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 ...

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 administere...

Eligibility Criteria

Inclusion

  • 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).

Exclusion

    Key Trial Info

    Start Date :

    August 8 2014

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    May 1 2018

    Estimated Enrollment :

    26 Patients enrolled

    Trial Details

    Trial ID

    NCT02222688

    Start Date

    August 8 2014

    End Date

    May 1 2018

    Last Update

    August 13 2020

    Active Locations (1)

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    UCSD Moores Cancer Center

    La Jolla, California, United States, 92093