Content - SAKK 36/13

SAKK 36/13 - Combined therapy for mantle cell lymphoma

Mantle cell lymphoma is one of the non-Hodgkin lymphomas, i.e. cancers that originate from immune cells. Various drugs are available to treat mantle cell lymphoma. Bortezomib and ibrutinib are two such drugs. These two active substances are currently used individually, i.e. not in combination, to treat mantle cell lymphoma.

The aim of trial SAKK 36/13 is to establish whether bortezomib and ibrutinib can be administered together. In this study, patients who have already received ineffective treatment for mantle cell lymphoma or who subsequently suffered a relapse will be treated with bortezomib and ibrutinib in combination.

Study Chair:

PD Dr. med. Urban Novak, Inselspital Bern, +41 31 632 19 92

  • Contacts at the hospitals

  • 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 [β-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

    • 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.

Locations for this trial:

Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Kantonsspital Baden
Im Ergel 1
4600 Baden
Freiburgstrasse 8
3010 Bern
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Centre Hospitalier Universitaire Vaudois CHUV
Rue du Bugnon 46
0 Lausanne
Kantonsspital Liestal
Rheinstrasse 26
0 4410 Liestal
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Kantonsspital Luzern
0 6000 Luzern
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Klinik Hirslanden Zürich
Witellikerstrasse 40
0 8032 Zürich
Klinik Hirslanden im Park
Seestrasse 259
0 8002 Zürich