Research study of Ibrutinib in Combination with Venetoclax in patients with Mantle Cell Lymphoma

Phase 1

• Conditions: Mantle Cell Lymphoma; MedDRA version: 20.0Level: PTClassification code 10061275Term: Mantle cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000129-12-CZ
• Lead Sponsor: Pharmacyclics LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-04
• Last Update Posted: 12 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 362

Inclusion Criteria

For SRI and Randomization Phase
Disease-Related
• Pathologically confirmed MCL (in tumor tissue), with documentation of
either overexpression of cyclin D1 in association with other relevant
markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14) as
assessed by cytogenetics, fluorescent in situ hybridization (FISH), or
polymerase chain reaction (PCR).
• At least 1 measurable site of disease that is =2.0 cm in the longest
diameter and measurable in 2 perpendicular dimensions per CT
• At least 1, but no more than 5, prior treatment regimens for MCL
including at least 1 prior rituximab/anti-CD20 containing regimen
• Failure to achieve at least partial response (PR) with, or documented
disease progression after, the most recent treatment regimen
• Subjects must have adequate fresh or paraffin embedded tissue.
Laboratory
• Adequate hematologic function
• Adequate hepatic and renal function
Demographic
• Men and women = 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status (PS)
of 0 or 1

For Treatment-naive Open-label Arm:
1. Pathologically confirmed treatment-naive MCL (tumor tissue), with
documentation of either overexpression of cyclin D1 in association with
other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of
t(11;14), as assessed by cytogenetics, fluorescent in situ hybridization
(FISH), or polymerase chain reaction (PCR)
• A report from the local laboratory is acceptable if available; however, it
must be reviewed and approved by the central pathology laboratory to
verify the above criteria prior to enrollment
• If the report from the local laboratory is not available, a tumor block or
slides must be sent to the central pathology laboratory for confirmation
of the MCL diagnosis prior to enrollment.
2. Men and women =18 years of age with a TP53 mutation
3. At least 1 measurable site of disease that is =2.0 cm in the longest
diameter and measurable in 2 perpendicular dimensions per CT
4. Subjects must have adequate fresh or paraffin-embedded tissue
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS)
of = 2
6. Adequate hematologic function independent of transfusion and growth
factor support for at least 7 days prior to first dose, with the exception of
pegylated G CSF (pegfilgrastim) and darbepoeitin which require at least
14 days prior to the first dose defined as:
• Absolute neutrophil count (ANC) >1000 cells/mm3 (1.0 x 109/L)
• Platelet count >50,000 cells/mm3 (50 x 109/L)
• Hemoglobin >8.0 g/dL
7. Adequate hepatic and renal function defined as:
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) =
3.0 x upper limit of normal (ULN)
• Estimated Creatinine Clearance (CrCl) =30 mL/min (Cockcroft-Gault)
• Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome
or of non hepatic origin)
8. Prothrombin time (PT) or International normal ratio (INR) <1.5 x
upper limit of normal (ULN) and PTT (activated partial thromboplastin
time [aPTT]) <1.5 x ULN (unless abnormalities are unrelated to
coagulopathy or bleeding disorder). When treated with warfarin or other
vitamin K antagonists, then INR =3.0
9. Male and female subjects of reproductive potential who agree to use
both a highly effective method of birth control (eg, implants, injectables,
combined oral contraceptives, some intrauterine devices [IUDs],
complete abstinence , or sterilized partner) and a barrier method (eg,
condoms, cervical ring, sponge, etc) during the period of therapy and for
90 days aft

Exclusion Criteria

For SRI and Randomization Phase
Disease-Related
• History or current evidence of central nervous system lymphoma
Concurrent Conditions
• Concurrent enrollment in another therapeutic investigational study or
prior therapy with ibrutinib or other BTK inhibitors
• Prior treatment with venetoclax or other BCL2 inhibitors
• Anticancer therapy including chemotherapy, radiotherapy, small
molecule and investigational agents =21 days prior to receiving the first
dose of study drug
• Treatment with any of the following within 7 days prior to the first
dose of study drug:
o moderate or strong cytochrome P450 3A (CYP3A) inhibitors
o moderate or strong CYP3A inducers

For Treatment-naive Open-label Arm:
1. Blastoid variant of MCL
2. History or current evidence of central nervous system lymphoma
3. Concurrent enrollment in another therapeutic investigational study or
prior therapy, including ibrutinib or other BTK inhibitors
4. Prior treatment with venetoclax or other BCL2 inhibitors
5. History of other malignancies, except:
• Malignancy treated with curative intent and with no known active
disease present for =3 years before the first dose of study drug and felt
to be at low risk for recurrence by treating physician
• Adequately treated non-melanoma skin cancer or lentigo maligna
without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
6. Vaccinated with live, attenuated vaccines within 4 weeks of the first
dose of study drug
7. Clinically significant infection requiring IV systemic treatment that
was completed =14 days before the first dose of study drug
8. Any uncontrolled active systemic infection
9. Known bleeding disorders (eg, von Willebrand's disease or
hemophilia)
10. History of stroke or intracranial hemorrhage within 6 months prior to
enrollment
11. Known history of human immunodeficiency virus (HIV) or active with
hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are
positive for hepatitis B core antibody, or hepatitis C antibody must have
a negative polymerase chain reaction (PCR) result before enrollment.
Those who are hepatitis B surface antigen (HBsAg) or PCR positive will
be excluded.
12. Major surgery within 4 weeks of the first dose of study drug.
13. Any life-threatening illness, medical condition, or organ system
dysfunction that, in the investigator's opinion, could compromise the
subject's safety or put the study outcomes at undue risk
14. Currently active, clinically significant cardiovascular disease, such as
uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as
defined by the New York Heart Association Functional Classification; or a
history of myocardial infarction, unstable angina, or acute coronary
syndrome within 6 months prior to randomization
15. Unable to swallow capsules or tablets, or malabsorption syndrome,
disease significantly affecting gastrointestinal function, or resection of
the stomach or small bowel, symptomatic inflammatory bowel disease or
ulcerative colitis, or partial or complete bowel obstruction
16. Treatment with any of the following within 7 days prior to the first
dose of study drug:
• Moderate or strong cytochrome P450 3A (CYP3A) inhibitors
• Moderate or strong CYP3A inducers
17. Administration or consumption of any of the following within 3 days
prior to the first dose of study drug:
• grapefruit or grapefruit products
• Seville oranges (including marmalade containing Seville oranges)
• star fruit
18. Known allergy to xanthine

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified