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

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Disease Information

Descriptive Information
Brief Title † A Study of the Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies
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
Brief Summary 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.
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.
Study Phase Phase 1/Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † Phase 1b: Recommended dosing regimen (RDR)
Secondary Outcome Measure † Phase 1b: Treatment Related Adverse Events
Condition † B-cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Mantle Cell Lymphoma
Intervention † DrugCirmtuzumab
Study Arms / Comparison Groups Phase 1b - Dose Finding Cirmutuzumab followed by Cirmtuzumab plus ibrutinib Phase 1b - Dose Expansion Cirmtuzumab plus ibrutinib Phase 2 - Cirmtuzumab plus ibrutinib Phase 2 safety and efficacy evaluation Phase 2 - Ibrutinib Phase 2 safety and efficacy evaluation
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 156
Start Date † August 1, 2017
Completion Date August 1, 2022
Primary Completion Date February 1, 2019
Eligibility 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.
Gender All
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts †† Teresa Rzesiewicz, RN, BSN, 844-317-STEM (7836), alphastemcellclinic@ucsd.edu
Location Countries † United States
Administrative Information
NCT ID † NCT03088878
Organization ID 170127
Secondary IDs ††
Responsible Party Principal Investigator
Study Sponsor † University of California, San Diego
Collaborators ††
Investigators † Principal Investigator: Catriona Jamieson, MD, PhD, University of California, San Diego
Information Provided By
Verification Date March 2017
First Received Date † March 2, 2017
Last Updated Date March 22, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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