B-cell Chronic Lymphocytic LeukemiaPhase 1/2NCT03088878
A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies
A Phase 1/2 study testing Cirmtuzumab (2-16 kg/mg) plus Ibrutinib, Cirmtuzumab (300mg) plus Ibrutinib and Cirmtuzumab (600 mg) plus ibrutinib in people with B-cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Oncternal Therapeutics, Inc at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- Cirmtuzumab (2-16 kg/mg) plus Ibrutinib, Cirmtuzumab (300mg) plus Ibrutinib and Cirmtuzumab (600 mg) plus ibrutinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 12 sitesUnited States
- Study dates
- 3 Jan 2018to 25 Sep 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 34Show fewer
- 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:
- Negative human immunodeficiency virus (HIV) antibody.
- 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.
- Negative hepatitis C virus (HCV) antibody or negative HCV RNA by quantitative PCR.
- For female patients of childbearing potential, a negative urine or serum pregnancy test prior to the start of study therapy.
- For female patients of childbearing potential, willingness to use a highly effective method of contraception from the start of the screening period until ≥3 months after the last dose of cirmtuzumab and ≥1 month after the last dose of ibrutinib, whichever is later. Note: A female patient 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 patients who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use an effective method of contraception from the start of study therapy until ≥3 months after the last dose of cirmtuzumab and ≥3 months after the last dose of ibrutinib, whichever is later and to refrain from sperm donation from the start of study therapy until ≥3 months after administration of the final dose of either of the study drugs. Note: A male patient 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 patient's cancer.
- Willingness and ability of the patient to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.
- Evidence of a personally signed informed consent indicating that the patient 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
The Christ Hospital Lindner Research Center
Cincinnati, Ohio, 45219
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
Hackensack Meridian Health, John Theurer Cancer Center
Hackensack, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
Sanford Stem Cell Clinical Center at UCSD
La Jolla, California, 92093
Yale Cancer Center
New Haven, Connecticut, 06510
Northwell Health
New Hyde Park, New York, 11042
Louisiana State University Health New Orleans (NCI Community Oncology Research Program)
New Orleans, Louisiana, 70112
Manhattan Hematology Oncology Research Foundation, Inc.
New York, New York, 10016
Columbia University Medical Center
New York, New York, 10032
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: A Phase 1b/2 Study of the ROR1-Targeting Monoclonal Antibody, Cirmtuzumab (UC-961), and the Bruton Tyrosine Kinase Inhibitor, Ibrutinib, in Patients With B-Cell Lymphoid Malignancies
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.
Read the detailed description
This is a Phase 1b/2 study to investigate the safety and effectiveness of the investigational drug, cirmtuzumab (INN:zilovertamab), 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 chronic lymphocytic leukemia /small lymphocytic leukemia (CLL/SLL), previously treated mantle cell lymphoma (MCL) subjects that are BTKI naiive or have received a prior Bruton tyrosine kinase (BTK) inhibitor therapy, unless they demonstrated primary or acquired resistance to BTKi. Up to 48 subjects will be enrolled in Part 1 to determine the recommended dosing regimen (RDR). In Part 2, up to 60 subjects (CLL/SLL, MCL and MZL (marginal zone lymphoma) 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. MZL subjects that have been previously treated and have relapsed after or progressed during at least one prior anti-CD20 -based therapy will be evaluated. In the Phase 2 (Part 3) portion of the study, approximately 30 subjects with CLL/SLL who may have received minimal prior BTK inhibitor therapy 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.
- Conditions
- B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
- Being tested
- Cirmtuzumab (2-16 kg/mg) plus Ibrutinib, Cirmtuzumab (300mg) plus Ibrutinib, Cirmtuzumab (600 mg) plus ibrutinib, Cirmtuzumab (RDR) plus ibrutinib, Cirmtuzumab plus ibrutinib
- Keywords
- Chronic lymphocytic leukemia, Small lymphocytic lymphoma, Mantle cell lymphoma, Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1), Bruton Tyrosine Kinase (BTK), Ibrutinib, Marginal zone lymphoma
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cirmtuzumab (2-16 kg/mg) plus IbrutinibDrug
Also called UC-961, Imbruvica
Participants will receive escalating doses of cirmtuzumab (2-16 mg/kg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 or 560 mg) orally once daily, starting at week 4.
Cirmtuzumab (300mg) plus IbrutinibDrug
Also called UC-961, Imbruvica
Participants will receive cirmtuzumab (300 mg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily.
Cirmtuzumab (600 mg) plus ibrutinibDrug
Also called UC-961, Imbruvica
Participants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily.
Cirmtuzumab (RDR) plus ibrutinibDrug
Also called UC-961, Imbruvica
Participants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter, plus ibrutinib (420 or 560 mg) orally once daily
Cirmtuzumab plus ibrutinibDrug
Also called UC-961, Imbruvica
Arm A: Participants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily.
Ibrutinib aloneDrug
Also called Imbruvica
Arm B: Participants will receive ibrutinib (420 mg) orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Cirmtuzumab followed by Cirmtuzumab plus ibrutinib Receives: Drug: Cirmtuzumab (2-16 kg/mg) plus Ibrutinib; Drug: Cirmtuzumab (300mg) plus Ibrutinib; Drug: Cirmtuzumab (600 mg) plus ibrutinib |
| Part 2 | Experimental | Cirmtuzumab plus ibrutinib Receives: Drug: Cirmtuzumab (RDR) plus ibrutinib |
| Part 3 - Arm A | Experimental | Cirmtuzumab plus ibrutinib Receives: Drug: Cirmtuzumab plus ibrutinib |
| Part 3 - Arm B | Active comparator | Ibrutinib only Receives: Drug: Ibrutinib alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response
Defined as achievement of complete response (CR), complete response with incomplete blood count recovery (CRi), partial response (PR), or partial response with lymphocytosis (PR-L) for those with CLL/SLL, per standardized criteria [Hallek 2008], as recently updated [Hallek 2018; Cheson 2012]; and the achievement of a CR or PR for those with MCL or MZL, per based on standardized criteria [Cheson 2007] as recently updated [Cheson 2014].
Measured: up to 5 years
Secondary outcomes (4)
Progression Free Survival (PFS)
Defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using Kaplan-Meier Survival Methods.
Measured: Up to 5 years
Overall Survival
Defined as the interval from the start of study therapy to death from any cause. Overall Survival was analyzed using Kaplan-Meier Survival methods.
Measured: Up to 5 years
Duration of Response
Defined as the amount of time (months) for achieving of complete response (CR), complete response with incomplete blood count recovery (CRi), partial response (PR), or partial response with lymphocytosis (PR-L) for those with CLL/SLL; and the amount of time (months) for achieving of a CR or PR for those with MCL.
Measured: Up to 5 years
Progression-free Survival (PFS) for Patients With TP53 Mutation Status
Defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause, in patients with TP53 mutation status
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2017
- Study start3 Jan 2018
- Primary completion25 Sep 2024
- Study completion25 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for B-cell Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncternal Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM), University of California, San Diego, Pharmacyclics LLC.
- Responsible party
- Sponsor
- Investigators
- Michael Choi, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03088878
- Sponsor's protocol ID
- CIRM-0001 (CIRLL)
- Status last verified
- Jan 2025
- First submitted
- 2 Mar 2017
- Last updated
- 12 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
PubMed 17242396Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
PubMed 25113753Choi MY, Ghia EM, Siddiqi T, Barrientos JC, Tuscano J, Koff JL, Yazji S, Leslie LA, Isufi I, Lamanna N, Goldenberg A, Chung G, Subbiah S, Robinson JM, O'Neill S, Jamieson CHM, Breitmeyer JB, Wierda WG, Kipps TJ. Inhibition of ROR1 signaling with zilovertamab plus ibrutinib in chronic lymphocytic leukemia: safety, mechanistic insights, and an exploratory signal in del(17p) disease. Leukemia. 2026 Oct 2. doi: 10.1038/s41375-026-03131-w. Online ahead of print.
PubMed 42827116Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.
PubMed 34398557
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of the ROR1-Targeting Monoclonal Antibody, Cirmtuzumab (UC-961), and the Bruton Tyrosine Kinase Inhibitor, Ibrutinib, in Patients With B-Cell Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT03088878
- Acronym / sponsor ID
- CIRM-0001 (CIRLL)
- Conditions
- B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
- Keywords
- Chronic lymphocytic leukemia, Small lymphocytic lymphoma, Mantle cell lymphoma, Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1), Bruton Tyrosine Kinase (BTK), Ibrutinib, Marginal zone lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Oncternal Therapeutics, IncIndustry (pharma, biotech, devices)
- Collaborators
- California Institute for Regenerative Medicine (CIRM), University of California, San Diego, Pharmacyclics LLC.
- Study start
- 3 Jan 2018 (actual)
- Primary completion
- 25 Sep 2024 (actual)
- Study completion
- 25 Sep 2024 (actual)
- First posted
- 23 Mar 2017 (actual)
- Results
- Posted 12 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase 1b/2 study to investigate the safety and effectiveness of the investigational drug, cirmtuzumab (INN:zilovertamab), 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 chronic lymphocytic leukemia /small lymphocytic leukemia (CLL/SLL), previously treated mantle cell lymphoma (MCL) subjects that are BTKI naiive or have received a prior Bruton tyrosine kinase (BTK) inhibitor therapy, unless they demonstrated primary or acquired resistance to BTKi. Up to 48 subjects will be enrolled in Part 1 to determine the recommended dosing regimen (RDR). In Part 2, up to 60 subjects (CLL/SLL, MCL and MZL (marginal zone lymphoma) 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. MZL subjects that have been previously treated and have relapsed after or progressed during at least one prior anti-CD20 -based therapy will be evaluated. In the Phase 2 (Part 3) portion of the study, approximately 30 subjects with CLL/SLL who may have received minimal prior BTK inhibitor therapy 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Cirmtuzumab (2-16 kg/mg) plus Ibrutinib, Drug: Cirmtuzumab (300mg) plus Ibrutinib, Drug: Cirmtuzumab (600 mg) plus ibrutinibCirmtuzumab followed by Cirmtuzumab plus ibrutinib |
| Part 2 | Experimental | Drug: Cirmtuzumab (RDR) plus ibrutinibCirmtuzumab plus ibrutinib |
| Part 3 - Arm A | Experimental | Drug: Cirmtuzumab plus ibrutinibCirmtuzumab plus ibrutinib |
| Part 3 - Arm B | Active comparator | Drug: Ibrutinib aloneIbrutinib only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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).
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cirmtuzumab (2-16 kg/mg) plus IbrutinibAlso: UC-961, ImbruvicaParticipants will receive escalating doses of cirmtuzumab (2-16 mg/kg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 or 560 mg) orally once daily, starting at week 4. | Drug | Part 1 |
| Cirmtuzumab (300mg) plus IbrutinibAlso: UC-961, ImbruvicaParticipants will receive cirmtuzumab (300 mg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily. | Drug | Part 1 |
| Cirmtuzumab (600 mg) plus ibrutinibAlso: UC-961, ImbruvicaParticipants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 5 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily. | Drug | Part 1 |
| Cirmtuzumab (RDR) plus ibrutinibAlso: UC-961, ImbruvicaParticipants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter, plus ibrutinib (420 or 560 mg) orally once daily | Drug | Part 2 |
| Cirmtuzumab plus ibrutinibAlso: UC-961, ImbruvicaArm A: Participants will receive cirmtuzumab (600 mg) administered IV every 2 weeks for 3 administrations and then every 4 weeks thereafter, plus ibrutinib (420 mg) orally once daily. | Drug | Part 3 - Arm A |
| Ibrutinib aloneAlso: ImbruvicaArm B: Participants will receive ibrutinib (420 mg) orally once daily | Drug | Part 3 - Arm B |
Primary outcome
Overall Response
Time frame: up to 5 years
Defined as achievement of complete response (CR), complete response with incomplete blood count recovery (CRi), partial response (PR), or partial response with lymphocytosis (PR-L) for those with CLL/SLL, per standardized criteria [Hallek 2008], as recently updated [Hallek 2018; Cheson 2012]; and the achievement of a CR or PR for those with MCL or MZL, per based on standardized criteria [Cheson 2007] as recently updated [Cheson 2014].
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: Up to 5 years
Overall Survival
Time frame: Up to 5 years
Duration of Response
Time frame: Up to 5 years
Progression-free Survival (PFS) for Patients With TP53 Mutation Status
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17242396Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
- Background: PubMed 25113753Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
- Derived from this study: PubMed 42827116Choi MY, Ghia EM, Siddiqi T, Barrientos JC, Tuscano J, Koff JL, Yazji S, Leslie LA, Isufi I, Lamanna N, Goldenberg A, Chung G, Subbiah S, Robinson JM, O'Neill S, Jamieson CHM, Breitmeyer JB, Wierda WG, Kipps TJ. Inhibition of ROR1 signaling with zilovertamab plus ibrutinib in chronic lymphocytic leukemia: safety, mechanistic insights, and an exploratory signal in del(17p) disease. Leukemia. 2026 Oct 2. doi: 10.1038/s41375-026-03131-w. Online ahead of print.
- Derived from this study: PubMed 34398557Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.
- Individual participant dataSharing planned: No
Related trials for B-cell Chronic Lymphocytic Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Choi, MD principal investigator
University of California, San Diego
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cirmtuzumab (2-16 kg/mg) plus Ibrutinib, Cirmtuzumab (300mg) plus Ibrutinib and Cirmtuzumab (600 mg) plus ibrutinib in people with B-cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Oncternal Therapeutics, Inc at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response (time frame: up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03088878, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2025.