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

Completed · Phase 1/Phase 2

Conditions studied: B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma

In brief

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 and lymphoma cells to grow and survive. ROR1 is rarely found on healthy cells.

Key facts

Study ID

NCT03088878

Run by

Oncternal Therapeutics, Inc

People needed

95

Starts

2018-01-03

Expected to finish

2024-09-25

Last updated by the study team

2025-02-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Men and women of age ≥18 years.
• ECOG performance status of 0, 1, or 2
• Histological diagnosis of CLL/SLL, MCL or MZL (including splenic,nodal and extranodal subtypes) as documented in medical records (pathology reports and slides or blocks should be available for review or additional testing).
• MCL has been previously treated and has relapsed after or progressed during prior therapy. CLL/SLL may have been previously treated or are treatment naïve but now require therapy. MZL has been previously treated and has relapsed after or progressed during at least one prior anti-CD20 -based therapy
• A medically appropriate candidate for ibrutinib treatment (based on the judgement of the clinical investigator).
• Patients who have received prior BTK inhibitor therapy are eligible, unless they demonstrated primary or acquired resistance to a BTK inhibitor or experienced a serious or severe adverse event attributed to BTK inhibitor therapy.
• Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 non-biopsied, non-irradiated lesion that measures >1.5 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 any Bcl-2 or PI3K inhibitor therapy, surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week (or ≥3 half-lives of the previous drug) 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 exceptions of alopecia, 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:
• Absolute neutrophil count (ANC) ≥1.0 × 109/L.
• Platelet count ≥50 × 109/L.
• Hemoglobin ≥8.0 g/dL maintained for ≥1 week from any prior transfusion.
• Adequate hepatic profile:
• Serum alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN).
• Serum aspartate aminotransferase (AST) ≤3 × ULN.
• Serum bilirubin ≤1.5 × ULN unless elevated due to Gilbert syndrome.
• Adequate renal function:
• Estimated creatinine clearance (eClCR) >30 mL/minute (with eClCR to be calculated by the Cockcroft-Gault formula [see Appendix 12.2]), or
• Measured creatinine clearance >30 mL/minute (as assessed with a 24-hour urine collection).
• Adequate coagulation profile:
• Prothrombin time (PT) ≤1.5 × ULN.
• Activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
• Negative viral serology:

You may not qualify if…

• Known histological transformation to an aggressive lymphoma (ie, Richter transformation).
• Known central nervous system malignancy.
• Presence of another cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
• 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, or Grade ≥2 bradycardia.
• 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.
• Contraindication for ibrutinib use because of bleeding diathesis.
• Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of study therapy. Note: Patients with localized fungal infections of skin or nails are not precluded from participation.
• In patients 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.
• Use of a moderate or strong inhibitor or inducer of cytochrome P450 (CYP) 3A4 within 7 days prior to the expected start of ibrutinib therapy.
• 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.

Where it is running

• City of Hope (City of Hope National Medical Center, City of Hope Medical Center) — Duarte, California, United States
• Sanford Stem Cell Clinical Center at UCSD — La Jolla, California, United States
• UC Davis Comprehensive Cancer Center — Sacramento, California, United States
• Yale Cancer Center — New Haven, Connecticut, United States
• Winship Cancer Institute of Emory University — Atlanta, Georgia, United States
• Louisiana State University Health New Orleans (NCI Community Oncology Research Program) — New Orleans, Louisiana, United States
• Hackensack Meridian Health, John Theurer Cancer Center — Hackensack, New Jersey, United States
• Northwell Health — New Hyde Park, New York, United States
• Manhattan Hematology Oncology Research Foundation, Inc. — New York, New York, United States
• Columbia University Medical Center — New York, New York, United States
• The Christ Hospital Lindner Research Center — Cincinnati, Ohio, United States
• MD Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.