HOVON 133 MCL/TRIANGLE: autologous Transplantation after a Rituximab/Ibrutinib/Ara-c containing iNduction in Generalized mantle cell Lymphoma - a randomized European MCL Network trial
- Conditions
- Mantle cell lymphomaMCL10025320
- Registration Number
- NL-OMON55612
- Lead Sponsor
- Klinikum der Universitat Munchen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 140
-Histologically confirmed diagnosis of MCL according to WHO classification
-Suitable for high-dose treatment including high-dose Ara-C
-Stage II-IV (Ann Arbor)
-Age >= 18 years and <= 65 years
-Previously untreated MCL
-At least 1 measurable lesion; in case of bone marrow infiltration only, bone
marrow aspiration and biopsy is mandatory for all staging evaluations.
-ECOG/WHO performance status <= 2
-The following laboratory values at screening (unless related to MCL):
-Absolute neutrophil count (ANC) >=1000 cells/µL
-Platelets >=100,000 cells/µL
-Transaminases (AST and ALT) <=3 x upper limit of normal (ULN)
-Total bilirubin <=2 x ULN unless due to known Morbus Meulengracht
[Gilbert-Meulengracht- Syndrome])
-Creatinine <=2 mg/dL or calculated creatinine clearance >= 50 mL/min
-Written informed consent form according to ICH/EU GCP and national
regulations
-Sexually active men and women of child-bearing potential must agree to use one
of
the highly effective contraceptive methods (combined oral contraceptives using
two
hormones, contraceptive implants, injectables, , intrauterine devices,
sterilized
partner) together with one of the barrier methods (latex condoms, diaphragms,
contraceptive caps) while on study; this should be maintained for 90 days after
the last dose of study drug and 12 months after the last dose of rituximab.
-Major surgery within 4 weeks prior to randomization.
-Requires anticoagulation with warfarin or equivalent vitamin K antagonists
(e.g. phenprocoumon).
-History of stroke or intracranial hemorrhage within 6 months prior to
randomization.
-Requires treatment with strong CYP3A4/5 inhibitors.
-Any life-threatening illness, medical condition, or organ system dysfunction
which, in the investigator*s opinion, could compromise the subject*s safety,
interfere with the absorption or metabolism of ibrutinib capsules, or put the
study outcomes at undue risk.
-Vaccinated with live, attenuated vaccines within 4 weeks prior to
randomization.
-Known CNS involvement of MCL
-Clinically significant hypersensitivity (e.g., anaphylactic or anaphylactoid
reactions to the compound of ibrutinib itself or to the excipients in its
formulation)
-Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to
murine antibodies
-Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody
or interferon except prephase therapy outlined in this trial protocol
-Serious concomitant disease interfering with a regular therapy according to
the study protocol:
-Cardiac (Clinically significant cardiovascular disease such as uncontrolled
or symptomatic arrhythmias, congestive heart failure, or myocardial infarction
within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe)
cardiac disease as defined by the New York Heart Association Functional
Classification or LVEF below LLN )
-Pulmonary (chronic lung disease with hypoxemia)
-Endocrinological (severe, not sufficiently controlled diabetes mellitus)
-Renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal
value and/or creatinine clearance < 50 ml/min)
-Impairment of liver function (unless caused by the lymphoma): transaminases
> 3x normal or bilirubin > 2,0 mg/dl unless due to Morbus Meulengracht
(Gilbert-Meulengracht-Syndrome)
-Positive test results for chronic HBV infection (defined as positive HBsAg
serology) (mandatory testing)
Patients with occult or prior HBV infection (defined as negative HBsAg and
positive total HBcAb) may be included if HBV DNA is undetectable, provided that
they are willing to undergo monthly DNA testing. Patients who have protective
titers of hepatitis B surface antibody (HBSAb) after
vaccination are eligible.
-Positive test results for hepatitis C (mandatory hepatitis C virus [HCV]
antibody serology testing). Patients positive for HCV antibody are eligible
only if PCR is negative for HCV RNA.
-Patients with known HIV positive infection (mandatory test).
-Prior organ, bone marrow or peripheral blood stem cell transplantation
-Concomitant or previous malignancies within the last 3 years other than basal
cell skin cancer or in situ uterine cervix cancer
-Pregnancy or lactation
-Any psychological, familial, sociological, or geographical condition
potentially hampering compliance with the study protocol and follow up schedule
-Subjects not able to give consent
-Subjects without legal capacity who are unable to understand the nature,
scope, significance and consequences of this clinical trial
-Participation in another clinical trial within 30 days before randomization in
this study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>FFS defined as time from randomization to stable disease at end of<br /><br>immuno-chemotherapy, progressive disease, or death from any cause.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Efficacy Endpoints:<br /><br>-Overall survival (OS)<br /><br>-Progression-free survival (PFS) from randomization, from end of induction<br /><br>immuno-chemotherapy in patients with CR or PR at end of induction<br /><br>immuno-chemotherapy, and from the staging 6 weeks after end of induction<br /><br>assessment (at month 6)<br /><br>-Overall response and complete remission rates at midterm, at end of induction,<br /><br>3 months after end of induction immuno-chemotherapy (at month 6)<br /><br>-PR to CR conversion rate during follow-up after end of induction<br /><br>immuno-chemotherapy<br /><br><br /><br>Secondary Toxicity Endpoints:<br /><br>-Rates of AEs, SAEs, and SUSARs by CTC grade (Version 4.03) during induction<br /><br>immuno-chemotherapy and during periods of follow-up after response to<br /><br>immune-chemotherapy<br /><br>-Cumulative incidence rates of SPMs </p><br>