Combination of Ibrutinib and Bortezomib to Treat Patients With Mantle Cell Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 28 June 2021
• Main ID: NCT02356458
• Date of registration: 02/02/2015
• Prospective Registration: Yes
• Primary sponsor: Swiss Group for Clinical Cancer Research
• Public title: Combination of Ibrutinib and Bortezomib to Treat Patients With Mantle Cell Lymphoma
• Scientific title: Combination of Ibrutinib and Bortezomib Followed by Ibrutinib Maintenance to Treat Patients With Relapsed and Refractory Mantle Cell Lymphoma; a Multicenter Phase I/II Trial.
• Date of first enrolment: August 31, 2015
• Target sample size: 58
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02356458
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Germany, Italy, Switzerland

Contacts

• Name: Urban Novak, PD Dr. med.
• Affiliation: University Hospital Bern - Inselspital

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patient must give written informed consent before registration indicating that the
patient understands the purpose of the procedures required for the trial and is
willing to participate in the trial.

- Histologically confirmed mantle cell lymphoma with either overexpression of cyclin D1
protein or evidence of t(11;14)(q13;q32) assessed by cytogenetics, by fluorescence, in
situ hybridization (FISH) or by polymerase chain reaction (PCR).

- Refractory or relapsed disease in need of systemic therapy after pretreatment with
non-bortezomib-containing chemotherapy (including high-dose therapy)

- At least one measurable lesion =11 mm in its greatest transverse diameter measured
with CT scan (contrast enhanced) or MRI (in case of the disease cannot be adequately
imaged using CT and if contrast is not appropriate for patients according to the
treating physician)

- WHO performance status 0-2

- Age = 18 years

- Adequate hematological values:

- Absolute neutrophil count (ANC) > 1.0 x 109/L independent of growth factor
support

- Platelets = 100 x 109/L or = 50 x 109/L if bone marrow involvement independent of
transfusion support in either situation,

- Hb = 80 g/L

- Adequate hepatic function:

- Total bilirubin =1.5xupper limit of normal (ULN) unless bilirubin is due to
Gilbert's syndrome = 5.0 x ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3xULN

- Adequate renal function: Body surface area (BSA) corrected creatinine clearance
>40mL/min/1.73m2 (calculated according to the formula of Cockcroft-Gault)

- Women of childbearing potential and men who are sexually active must be practicing a
highly effective method of birth control during and after the trial (see below)
consistent with local regulations regarding the use of birth control methods for
patients participating in clinical trials (see section 9.12). Men must agree to not
donate sperm during and after the trial. These restrictions apply for

- Ibrutinib: 3 month after the last dose of trial drug for males and 1 month for
females.

- Bortezomib: during trial treatment (for males and females): no restrictions of
birth control after last dose of trial drug. Donation of sperm: 6 month after the
last dose of trial drug.

- Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [ß-hCG]) or urine pregnancy test at baseline. Women who are pregnant or
breastfeeding are ineligible for this trial.

Exclusion Criteria:

- Prior therapy with ibrutinib or bortezomib

- Adverse event neuropathy of prior therapy grade =2 (according to CTCAE criteria) at
registration

- Previous malignancy within 5 years with the exception of adequately treated in situ
cervical cancer or localized non-melanoma skin cancer.

- Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningeosis)

- Evidence of ongoing systemic infections of all kind

- Exclusion of the following prior treatments prior to trial registration

- major surgery within 4 weeks

- concurrent treatment with other experimental drugs or treatment in a clinical
trial within 30 days.

- treatment with chemotherapy and radiotherapy within = 3 weeks

- vaccinated with live, attenuated vaccines within 4 weeks

- History of stroke or intracranial hemorrhage within 6 months prior to trial
registration.

- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g.
phenprocoumon)

- Requires treatment with strong or moderate CYP3A inhibitors (see
http://medicine.iupui.edu/)

- Clinically significant cardiovascular disease such as congestive heart failure NYHA
III or IV (as defined by the New York Heart Association Functional Classification),
uncontrolled or symptomatic arrhythmias, significant QT-prolongation, unstable angina
pectoris myocardial infarction within 6 months of prior to registration,

- Known history of human immunodeficiency virus (HIV) or active Hepatitis C virus or
active Hepatitis B virus infection or any uncontrolled active systemic infection
requiring treatment.

- Prior allogeneic bone marrow or solid organ transplantation

- Any life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator's opinion,

- could impair the ability of the patient to participate in the trial

- could compromise the patient's safety,

- could interfere with the absorption or metabolism of ibrutinib capsules, or

- could put the trial outcomes at undue risk

- could prevent compliance with trial treatment.

- Psychiatric disorder precluding understanding of trial information, giving informed
consent, or interfering with compliance for oral drug intake.

- Known hypersensitivity to trial drug(s) or hypersensitivity to any other component of
the trial drugs.

- Any concomitant drugs contraindicated for use with the trial drugs according to the
approved product information.

- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the trial protocol and follow-up.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Mantle Cell Lymphoma

Intervention(s)

Drug: bortezomib

Drug: Ibrutinib

Primary Outcome(s)

Phase I: Dose limiting toxicity (DLT) observed during the first cycle of trial treatment [Time Frame: At day 8, 14, 21 during cycle 1 (1 cycle = 21 days)]

Phase II: Overall response (OR) (combination therapy) [Time Frame: 4 1/2 months after registration.]

Secondary ID(s)

SAKK 36/13

2014-003893-17

SNCTP000001235

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

European Mantle Cell Lymphoma Network