Combination of ibrutinib and bortezomib followed by ibrutinib to treat patients with relapsed and refractory mantle cell lymphoma
- Conditions
- Histologically confirmed mantle cell lymphoma in need of systemictreatmentRefractory or relapsed disease after pretreatment of non-bortezomib containingchemotherapy including high-dose therapyMedDRA version: 20.0Level: PTClassification code 10026801Term: Mantle cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10026800Term: Mantle cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003893-17-DE
- Lead Sponsor
- SAKK, Swiss Group for Clinical Cancer Research
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 49
6.1.1 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.
6.1.2 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).
6.1.3 Refractory or relapsed disease in need of systemic therapy after
pretreatment with non-bortezomib-containing chemotherapy (including
high-dose therapy plus autologous stem cell support; induction and
consolidation with high-dose chemotherapy is considered one line of
chemotherapy.)
6.1.4 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).
6.1.5 WHO performance status 0-2 (see 0)
6.1.6 Age = 18 years
6.1.7 Adequate hematological values:
o Absolute neutrophil count (ANC) = 1.0 x 10^9/L independent of
growth factor support
o Platelets = 100 x 10^9/L or = 50 x 10^9/L if bone marrow
involvement independent of transfusion support in either situation,
o Hb = 80 g/L
6.1.8 Adequate hepatic function:
o Total bilirubin =1.5xupper limit of normal (ULN) unless bilirubin is
due to Gilbert`s syndrome = 5.0 x ULN
o Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) =3xULN
6.1.9 Adequate renal function: Body surface area (BSA) corrected
creatinine clearance =40mL/min/1.73m^2 (calculated according to the
corrected formula of Cockcroft-Gault, see 0)
6.1.10 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. Men must agree to not donate sperm
during and after the trial. These restrictions apply for
o Ibrutinib: 3 month after the last dose of trial drug for males and 1
month for females.
o 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.
6.1.11 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 49
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
6.2.1 Prior therapy with ibrutinib or bortezomib
6.2.2 Adverse event neuropathy of prior therapy grade =2 (according
to CTCAE criteria Version 4.0) at registration
6.2.3 Previous malignancy within 5 years with the exception of
adequately treated in situ cervical cancer or localized non-melanoma
skin cancer.
6.2.4 Presence or history of CNS disease (either CNS lymphoma or
lymphomatous meningeosis)
6.2.5 Evidence of ongoing systemic infections of all kind
6.2.6 Exclusion of the following prior treatments prior to trial
registration
o major surgery within 4 weeks
o concurrent treatment with other experimental drugs or treatment in
a clinical trial within 30 days.
o treatment with chemotherapy and radiotherapy within 3 weeks
o vaccinated with live, attenuated vaccines within 4 weeks
6.2.7 History of stroke or intracranial hemorrhage within 6 months
prior to trial registration.
6.2.8 Requires anticoagulation with warfarin or equivalent vitamin K
antagonists (e.g. phenprocoumon)
6.2.9 Requires treatment with strong or moderate CYP3A inhibitors
(see http://medicine.iupui.edu/clinpharm/ddis/main-table and also
chapter 9.11.1.2 of the study protocol)
6.2.10 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,
6.2.11 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.
6.2.12 Prior allogeneic bone marrow or solid organ transplantation
6.2.13 Any life-threatening illness, medical condition, or organ system
dysfunction which, in the investigator's opinion,
o could impair the ability of the patient to participate in the trial
o could compromise the patient's safety,
o could interfere with the absorption or metabolism of ibrutinib
capsules, or
o could put the trial outcomes at undue risk
o could prevent compliance with trial treatment.
6.2.14 Psychiatric disorder precluding understanding of trial
information, giving informed consent, or interfering with compliance
for oral drug intake.
6.2.15 Known hypersensitivity to trial drug(s) or hypersensitivity to
any other component of the trial drugs.
6.2.16 Any concomitant drugs contraindicated for use with the trial
drugs according to the approved product information.
6.2.17 Any psychological, familial, sociological or geographical
condition potentially hampering compliance with the trial protocol and follow-up.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the phase II is to define the efficacy of<br>ibrutinib in combination with bortezomib in patients with relapsed or<br>refractory Mantle cell Lymphoma;Secondary Objective: The secondary objectives of this trial are<br>• to determine the safety and tolerability of the RP2D of ibrutinib in<br>combination with bortezomib<br>• to determine the efficacy of ibrutinib in combination with<br>bortezomib in patients with relapsed MCL followed by an ibrutinib<br>maintenance therapy.;Primary end point(s): Overall response (OR) (combination therapy);Timepoint(s) of evaluation of this end point: 6 months after treatment start
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Adverse events (AE) until 30 days after end of trial therapy<br>• OR based on best response observed during treatment<br>(combination and maintenance therapy)<br>• Progression-free survival (PFS)<br>• Time to treatment failure (TTF)<br>• Duration of objective response;Timepoint(s) of evaluation of this end point: -OR at 1 1/2 years after patient registration. <br>-all other secondary endpoints estimated after 2 years<br>