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Trial record 2 of 3 for:    UCSD | cirmtuzumab

A Study of the Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies

This study is not yet open for participant recruitment.
Verified November 2017 by Catriona Jamieson, University of California, San Diego
Sponsor:
ClinicalTrials.gov Identifier:
NCT03088878
First Posted: March 23, 2017
Last Update Posted: November 15, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Oncternal Therapeutics, Inc
Information provided by (Responsible Party):
Catriona Jamieson, University of California, San Diego
  Purpose
This is Phase 1b/2 study to investigate the safety and effectiveness of the investigational drug, cirmtuzumab, when given in combination with ibrutinib in patients with B-cell lymphoid malignancies. Cirmtuzumab is a monoclonal antibody that attaches to a protein (called ROR 1) that is found on hematologic tumor cells. ROR1 has been shown to play a role in cell signaling that cause leukemia cells to grow and survive. ROR1 is rarely found on healthy cells.

Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Mantle Cell Lymphoma Drug: Cirmtuzumab Drug: Ibrutinib Drug: Cirmtuzumab plus ibrutinib Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of the ROR1-Targeting Monoclonal Antibody, Cirmtuzumab, and the Bruton Tyrosine Kinase Inhibitor, Ibrutinib, in Patients With B-Cell Lymphoid Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Phase 1b: Recommended dosing regimen (RDR) [ Time Frame: From baseline to 52 weeks ]
    Evaluation of cirmtuzumab dose-pharmacodynamic and pharmacokinetic-pharmacodynamic relationships, and safety

  • Phase 2: Complete Response (CR) rate [ Time Frame: From randomization to discontinuation of treatment of all study subjects or 72 weeks after accrual of the final subject ]
    Proportion of subjects achieving a CR in accordance with pre-established response criteria for lymphoma (Cheson 2007; Cheson 2014)


Secondary Outcome Measures:
  • Phase 1b: Treatment Related Adverse Events [ Time Frame: From baseline to 52 weeks ]
    Number of participants with adverse events and clinical laboratory abnormalities assessed by CTCAE v.4.03

  • Phase 2: Cirmtuzumab Plasma Concentration [ Time Frame: From randomization to discontinuation of treatment of all study subjects or 72 weeks after accrual of the final subject ]
    Concentrations measured using a validated immunoassay

  • Phase 2: ROR1 Cell Surface Expression [ Time Frame: From randomization to discontinuation of treatment of all study subjects or 72 weeks after accrual of the final subject ]
    Changes in ROR1 cell surface expression on malignant cells in peripheral blood and bone marrow.

  • Phase 2: Duration of Response [ Time Frame: From randomization to discontinuation of treatment of all study subjects or 72 weeks after accrual of the final subject ]
    The interval from the first documentation of objective response to the earlier of the first documentation of disease progression or death from any cause

  • Phase 2: Progression Free Survival [ Time Frame: From randomization to discontinuation of treatment of all study subjects or 72 weeks after accrual of the final subject ]
    The interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause

  • Phase 2: Time to Treatment Failure [ Time Frame: From randomization to discontinuation of treatment of all study subjects or 72 weeks after accrual of the final subject ]
    The interval from start of study therapy to the earliest of the first documentation of disease progression, the permanent cessation of study drug due to an adverse event, or death from any cause

  • Phase 2: Overall Survival [ Time Frame: From randomization to discontinuation of treatment of all study subjects or 72 weeks after accrual of the final subject ]
    The interval from the start of study therapy to death from any cause


Estimated Enrollment: 156
Anticipated Study Start Date: December 1, 2017
Estimated Study Completion Date: December 1, 2022
Estimated Primary Completion Date: April 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1b - Dose Finding
Cirmutuzumab followed by Cirmtuzumab plus ibrutinib
Drug: Cirmtuzumab
Administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter
Other Name: UC-961
Drug: Cirmtuzumab plus ibrutinib
  • Cirmtuzumab: Administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter
  • Ibrutinib: Self-administered orally once daily
Other Names:
  • UC-961
  • Imbruvica
Experimental: Phase 1b - Dose Expansion
Cirmtuzumab plus ibrutinib
Drug: Cirmtuzumab plus ibrutinib
  • Cirmtuzumab: Administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter
  • Ibrutinib: Self-administered orally once daily
Other Names:
  • UC-961
  • Imbruvica
Experimental: Phase 2 - Cirmtuzumab plus ibrutinib
Phase 2 safety and efficacy evaluation
Drug: Cirmtuzumab plus ibrutinib
  • Cirmtuzumab: Administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter
  • Ibrutinib: Self-administered orally once daily
Other Names:
  • UC-961
  • Imbruvica
Active Comparator: Phase 2 - Ibrutinib
Phase 2 safety and efficacy evaluation
Drug: Ibrutinib
Self-administered orally once daily
Other Name: Imbruvica

Detailed Description:
This is a Phase 1b/2 study to investigate the safety and effectiveness of the investigational drug, cirmtuzumab, when given in combination with ibrutinib in patients with B-cell lymphoid malignancies. The Phase 1b will be conducted in two parts (Part 1 and Part 2). Part 1 is a dose-finding evaluation of the sequential administration of cirmtuzumab monotherapy followed by cirmtuzumab and ibrutinib combination therapy in previously treated chronic lymphocytic leukemia /small lymphocytic leukemia (CLL/SLL) or mantle cell lymphoma (MCL) subjects who have not received prior Bruton tyrosine kinase (BTK) inhibitor therapy. Up to 48 subjects will be enrolled in Part 1 to determine the recommended dosing regimen (RDR). In Part 2, up to 18 subjects will be enrolled to further evaluate the safety and pharmacology of the cirmtuzumab and ibrutinib combination given at the RDR determined in Part 1 of the study. In the Phase 2 (Part 3) portion of the study, approximately 90 subjects with MCL will be randomized to either Arm 1 (cirmtuzumab and ibrutinib) at the RDR or Arm 2 (ibrutinib alone) to evaluate the clinical activity and safety of the two arms.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Histological diagnosis of CLL/SLL or MCL as documented in medical records
  • CLL/SLL or MCL has been previously treated and has relapsed after or progressed during prior therapy
  • No history of prior BTK-inhibitor-containing therapy
  • A medically appropriate candidate for ibrutinib treatment (based on the judgement of the clinical investigator)
  • Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 non-biopsied, non-irradiated lesion that measures ≥2.0 cm in the longest dimension [LD] and ≥1.0 cm in the longest perpendicular dimension [LPD] as assessed by computed tomography [CT] or magnetic resonance imaging [MRI]).
  • Current medical need for therapy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or progressive disease.
  • Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer 1 week before the start of study therapy.
  • All acute toxic effects of any prior antitumor therapy resolved to Grade 1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], or neurotoxicity [Grade 1 or 2 permitted], or selected laboratory parameters [Grade 1 or Grade 2 permitted with exceptions as noted below]).
  • Adequate bone marrow function:

    a) Absolute neutrophil count (ANC) ≥1.0 × 109/L (Grade ≤2). b) Platelet count ≥50 × 109/L (Grade ≤2). b) Hemoglobin ≥8.0 g/dL (Grade ≤2) maintained for ≥1 week from any prior transfusion.

  • Note: Grade ≥3 neutropenia, thrombocytopenia, or anemia is permitted if the abnormality is related to bone marrow involvement with hematological malignancy (as documented by bone marrow biopsy/aspirate obtained since the last prior therapy).
  • Adequate hepatic profile:

    1. Serum alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN) (Grade ≤1).
    2. Serum aspartate aminotransferase (AST) ≤3 × ULN (Grade ≤1).
    3. Serum bilirubin ≤1.5 × ULN (Grade ≤ 1).
  • Adequate renal function:

    a) Estimated creatinine clearance (eClCR) >45 mL/minute (with eClCR to be calculated by the Cockcroft-Gault formula), or b) Measured creatinine clearance >45 mL/minute (as assessed with a 24-hour urine collection).

    2. Adequate coagulation profile:

    1. Prothrombin time (PT) ≤1.5 × ULN (Grade ≤1).
    2. Activated partial thromboplastin time (aPTT) ≤1.5 × ULN (Grade ≤1).
  • Negative viral serology:

    1. Negative human immunodeficiency virus (HIV) antibody.
    2. Negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) antibody or undetectable hepatitis B (HBV) deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (PCR) testing.
    3. Negative hepatitis C virus (HCV) antibody or negative HCV ribonucleic acid (RNA) by quantitative PCR.
  • For female subjects of childbearing potential, a negative urine or serum pregnancy test prior to the start of study therapy.
  • For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of the screening period until ≥30 days after the final dose of study therapy. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin [βHCG]); or is menopausal (age ≥50 years with amenorrhea for ≥6 months).
  • For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception: willingness to use a protocol-recommended method of contraception from the start of study therapy until ≥30 days after the final dose of study therapy and to refrain from sperm donation from the start of study therapy until ≥90 days after administration of the final dose of study therapy. Note: A male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.
  • In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer.
  • Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures (including all bone marrow biopsy/aspirations and radiographic studies), and study restrictions.
  • Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.

Exclusion Criteria:

  • Known histological transformation to an aggressive lymphoma (ie, Richter transformation). Note: Biopsy documentation of the absence or presence of transformation is not required.
  • Known central nervous system malignancy. Note: Central nervous system imaging is only required in subjects with suspected central nervous system malignancy.
  • For study participants in Part 3: History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; adequately treated carcinoma in situ without evidence of disease; adequately treated, papillary, noninvasive bladder cancer; other cancer that has been in complete remission for ≥2 years.
  • Significant cardiovascular disease (eg, myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; or uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy.
  • Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle branch block, 2nd-degree atrioventricular (AV) block type II, 3rd-degree AV block, Grade ≥2 bradycardia, or corrected QT (QTc) >450 msec (for men) or >470 msec (for women).
  • Gastrointestinal disease (eg, gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that might interfere with drug absorption or with interpretation of gastrointestinal AEs.
  • Ongoing risk for bleeding due to active peptic ulcer disease; bleeding diathesis; or requirement for systemic anticoagulation with an antiplatelet drug (eg, aspirin, triflusal, clopidogrel, prasugrel, ticagrelor, ticlopidine, cilostazol, vorapaxar, dipyridamole); or with heparin, low-molecular-weight heparin or heparin fractions (eg, enoxaparin, dalteparin, fondaparinux) or oral anticoagulants (eg, apixaban, rivaroxaban, dabigatran etexilate, warfarin). Note: Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.
  • Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of study therapy. Note: Subjects with localized fungal infections of skin or nails are not precluded from participation.
  • In subjects with prior hematopoietic progenitor cell transplantation, evidence of ongoing graft-versus-host disease (GVHD).
  • Pregnancy or breastfeeding.
  • Major surgery within 4 weeks before the start of study therapy.
  • Prior solid organ transplantation.
  • Prior anti-ROR1 therapy within 12 weeks prior to the start of study therapy.
  • Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids. Note: At Screening, subjects may be using topical or inhaled corticosteroids. During study therapy, use of corticosteroids as prophylaxis for infusion reactions will be minimized. However, subjects may use systemic, enteric, topical or enteric corticosteroids as required for treatment-emergent conditions.
  • Use of a moderate or strong inhibitor or inducer of cytochrome P450 (CYP) 3A4 within 7 days prior to the start of study therapy (Study Parts 2 or 3) or expected requirement for use of a moderate or strong CYP3A4 inhibitor or inducer during study therapy (Study Parts 1, 2, or 3).
  • Use within 7 days prior to the start of study therapy of a drug known to prolong the QT interval (Study Parts 1 or 2) .
  • Concurrent participation in another therapeutic or imaging clinical trial. Any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a subject's ability to provide informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03088878


Contacts
Contact: Teresa Rzesiewicz, RN, BSN 844-317-STEM (7836) alphastemcellclinic@ucsd.edu

Locations
United States, California
UCSD Moores Cancer Center
La Jolla, California, United States, 92093
Sponsors and Collaborators
University of California, San Diego
Oncternal Therapeutics, Inc
Investigators
Principal Investigator: Catriona Jamieson, MD, PhD University of California, San Diego
  More Information

Publications:
Responsible Party: Catriona Jamieson, Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03088878     History of Changes
Other Study ID Numbers: 170127
First Submitted: March 2, 2017
First Posted: March 23, 2017
Last Update Posted: November 15, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Catriona Jamieson, University of California, San Diego:
Chronic lymphocytic leukemia
Small lymphocytic lymphoma
Mantle cell lymphoma
Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1)
Bruton Tyrosine Kinase (BTK)

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