A Study of Cirmtuzumab and Ibrutinib in Patients With B-C... | NCT03088878

Name	Class
California Institute for Regenerative Medicine (CIRM)	OTHER
University of California, San Diego	OTHER
Pharmacyclics LLC.	INDUSTRY

Label	Type	Description	Intervention Names
Part 1	Experimental	Cirmtuzumab followed by Cirmtuzumab plus ibrutinib	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	Drug: Cirmtuzumab (RDR) plus ibrutinib
Part 3 - Arm A	Experimental	Cirmtuzumab plus ibrutinib	Drug: Cirmtuzumab plus ibrutinib
Part 3 - Arm B	Active Comparator	Ibrutinib only	Drug: Ibrutinib alone

Name	Type	Description	Arm Group Labels	Other Names
Cirmtuzumab (2-16 kg/mg) plus Ibrutinib	Drug	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.

Measure	Description	Time Frame
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].	up to 5 years

Measure	Description	Time Frame
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.	Up to 5 years
Overall Survival

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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:
1. Absolute neutrophil count (ANC) ≥1.0 × 109/L.
2. Platelet count ≥50 × 109/L.
3. Hemoglobin ≥8.0 g/dL maintained for ≥1 week from any prior transfusion.
Adequate hepatic profile:
1. Serum alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN).
2. Serum aspartate aminotransferase (AST) ≤3 × ULN.
3. Serum bilirubin ≤1.5 × ULN unless elevated due to Gilbert syndrome.
Adequate renal function:
1. Estimated creatinine clearance (eClCR) >30 mL/minute (with eClCR to be calculated by the Cockcroft-Gault formula [see Appendix 12.2]), or
2. Measured creatinine clearance >30 mL/minute (as assessed with a 24-hour urine collection).
Adequate coagulation profile:
1. Prothrombin time (PT) ≤1.5 × ULN.
2. Activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
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 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.

Exclusion Criteria:

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.

Name	Affiliation	Role
Michael Choi, MD	University of California, San Diego	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)		Duarte	California	91010	United States

PubMed Identifier	Type	Citation	Retractions
17242396	Background	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.
25113753

ID	Title	Description
FG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Apr 15, 2022

Arm/Group Information

ID	Title	Description
BG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG001	MCL Phase 1b, Part 1: 4mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG002	MCL Phase 1b, Part 1: 8mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG003	MCL Phase 1b, Part 1: 16 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG004	MCL Phase 1b, Part 2: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG005	CLL Phase 1b, Part 1: 2 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG006	CLL Phase 1b, Part 1: 4 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG007	CLL Phase 1b, Part 1: 8 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG008	CLL Phase 1b, Part 1: 16 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG009	CLL Phase 1b, Part 1: 300 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG010	CLL Phase 1b, Part 1: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG011	CLL Phase 1b, Part 2: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
BG012	CLL Phase 2, Part 3: 600 mg	Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list: Arm A: cirmtuzumab + ibrutinib Arm B: ibrutinib alone
BG013	CLL Phase 2, Part 3: Ibrutinib Alone	Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list: Arm A: cirmtuzumab + ibrutinib Arm B: ibrutinib alone
BG014	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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].

The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.

Posted

Count of Participants

Participants

up to 5 years

ID	Title	Description
OG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG001	MCL Phase 1b, Part 1: 4mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG002	MCL Phase 1b, Part 1: 8mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG003	MCL Phase 1b, Part 1: 16 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG004	MCL Phase 1b, Part 2: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG005	CLL Phase 1b, Part 1: 2 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG006	CLL Phase 1b, Part 1: 4 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG007	CLL Phase 1b, Part 1: 8 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG008	CLL Phase 1b, Part 1: 16 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG009	CLL Phase 1b, Part 1: 300 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG010	CLL Phase 1b, Part 1: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG011	CLL Phase 1b, Part 2: 600mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG012	CLL Phase 2, Part 3: 600 mg	Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list: Arm A: cirmtuzumab + ibrutinib Arm B: ibrutinib alone
OG013	CLL Phase 2, Part 3: Ibrutinib Alone	Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list: Arm A: cirmtuzumab + ibrutinib Arm B: ibrutinib alone

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003 OG0013 OG0023 OG003

Secondary

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.

The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.

Posted

Median

95% Confidence Interval

months

Up to 5 years

ID	Title	Description
OG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG001	MCL Phase 1b, Part 1: 4mg/kg

Secondary

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.

The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.

Posted

Median

95% Confidence Interval

months

Up to 5 years

ID	Title	Description
OG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).
OG001	MCL Phase 1b, Part 1: 4mg/kg

Secondary

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.

The subset of the efficacy population achieving Objective Response (ORR). The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.

Posted

Median

95% Confidence Interval

months

Up to 5 years

ID	Title	Description
OG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).

Secondary

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

A subset of the efficacy population with a positive Del(17p) mutation. The efficacy population consists of enrolled subjects who have received at least one dose of either cirmtuzumab or ibrutinib and at least one tumor assessment.

Posted

Median

95% Confidence Interval

months

Up to 5 years

ID	Title	Description
OG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MCL Phase 1b, Part 1: 2mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	0	3	1	3	3	3
EG001	MCL Phase 1b, Part 1: 4mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	1	3	2	3	3	3
EG002	MCL Phase 1b, Part 1: 8mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	3	3	0	3	3	3
EG003	MCL Phase 1b, Part 1: 16 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	1	3	2	3	3	3
EG004	MCL Phase 1b, Part 2: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	7	21	13	21	21	21
EG005	CLL Phase 1b, Part 1: 2 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	1	3	3	3	3	3
EG006	CLL Phase 1b, Part 1: 4 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	0	3	1	3	3	3
EG007	CLL Phase 1b, Part 1: 8 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	1	3	2	3	3	3
EG008	CLL Phase 1b, Part 1: 16 mg/kg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	0	3	1	3	3	3
EG009	CLL Phase 1b, Part 1: 300 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	1	3	2	3	3	3
EG010	CLL Phase 1b, Part 1: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	0	3	2	3	3	3
EG011	CLL Phase 1b, Part 2: 600 mg	Part 1: Cirmtuzumab given by IV infusion every 2 weeks for 5 administrations (Weeks 0, 2, 4, 6, 8) and then every 4 weeks thereafter (Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52) at a dose of either 2, 4, 8, or 16 mg/kg. After establishment of safety at these dose levels, fixed doses of 300 and 600 mg IV per dose will be examined in patients with CLL/SLL. Ibrutinib self-administered orally, QD, continuously starting in Week 4 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL). Part 2: Cirmtuzumab given by IV infusion every 2 weeks for 3 administrations (Weeks 0, 2, 4) and then every 4 weeks thereafter (Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52) using the RDR of cirmtuzumab (600 mg fixed dose IV). Ibrutinib self-administered orally QD, continuously starting concurrently with cirmtuzumab in Week 0 at a dose of either 420 mg/day (for patients with CLL/SLL) or at a dose of 560 mg/day (for patients with MCL or MZL).	1	16	5	16	15	16
EG012	CLL Phase 2, Part 3: 600 mg	Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list: Arm A: cirmtuzumab + ibrutinib Arm B: ibrutinib alone	3	18	9	18	18	18
EG013	CLL Phase 2, Part 3: Ibrutinib Alone	Part 3 comprises a Phase 2 open-label, randomized, controlled, 2-arm, parallel-group evaluation of the clinical activity and safety of cirmtuzumab + ibrutinib versus ibrutinib alone. Patients with CLL/SLL will be randomized 2:1 to one of the following 2 regimens in blocks of 6 patients using a pre-generated randomization list: Arm A: cirmtuzumab + ibrutinib Arm B: ibrutinib alone	1	10	5	10	9	10

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial Fibrillation	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG0031 events1 affected3 at risk EG0041 events1 affected21 at risk EG0051 events1 affected3 at risk EG0060 events0 affected3 at risk EG0070 events0 affected3 at risk EG0081 events1 affected3 at risk EG0090 events0 affected3 at risk EG0100 events0 affected3 at risk EG0110 events0 affected16 at risk EG0122 events2 affected18 at risk EG0131 events1 affected10 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Basal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Campylobacter Gastroenteritis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cellulitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cellulitis Staphylococcal	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Cerebrovascular Accident	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Corona Virus Infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Erosive Oesophagitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypnonatraemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Neoplasm Progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Odema Peripheral	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pericardial Effusion	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Respiratory Failure	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Squamous Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Staphylococcal Infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Thyroid Cancer Metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tumor Lysis Syndrome	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vestibular Disorder	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Angina Pectoris	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cardiac Tamponade	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pericardial Haemorrhage	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Acute Sinusitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Coronavirus Test Positive	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Lung Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Neuroendocrine Tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Urinary Retention	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Prostatomegaly	Reproductive system and breast disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Atheroembolism	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Asthenia	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Eschericha Urinary Tract Infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypertensive Crisis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Autoimmune Haemolytic Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Pseudohyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003

ID	Term
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D020522	Lymphoma, Mantle-Cell
D018442	Lymphoma, B-Cell, Marginal Zone

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D016393	Lymphoma, B-Cell

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG0033 events2 affected3 at risk EG0048 events6 affected21 at risk EG0050 events0 affected3 at risk EG0061 events1 affected3 at risk EG0070 events0 affected3 at risk EG0081 events1 affected3 at risk EG0092 events1 affected3 at risk EG0101 events1 affected3 at risk EG0113 events3 affected16 at risk EG0126 events3 affected18 at risk EG0131 events1 affected10 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events3 affected3 at risk EG0021 events1 affected3 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected3 at risk EG003
Atrial Fibrillation	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0007 events3 affected3 at risk EG0011 events1 affected3 at risk EG0025 events3 affected3 at risk EG003
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG0007 events3 affected3 at risk EG0014 events3 affected3 at risk EG0022 events2 affected3 at risk EG003