Efficacy and safety of Rituximab, high-dose ARA-C and Dexamethasone (R-HAD) alone or in combination with Bortezomib in patients with relapsed or refractory mantle cell lymphoma A randomized Phase III Trial of the European MCL Network

Phase 1

• Conditions: Treatment of relapsed or refractory Mantle Cell Lymphoma; MedDRA version: 20.0Level: PTClassification code 10029601Term: Non-Hodgkin's lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10029600Term: Non-Hodgkin's lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2005-005144-62-DE
• Lead Sponsor: Klinikum der Ludwigs-Maximilians-Universität München

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-10-26
• Last Update Posted: 6 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 175

Inclusion Criteria

Each subject must fulfill all of the following inclusion criteria before enrollment to the study:
- Confirmed pathological diagnosis of MCL according to WHO classification.
- Relapse or progression following 1 to 3 prior lines of anti-neoplastic standard therapy. Therapy in remission after initial induction like intensified chemotherapy for stem cell separation followed by myeloablative therapy or any kind of maintenance therapy is classified as one line of therapy with the induction therapy
- If Rituximab was part of prior induction treatment, documented time to progression must be at least 12 weeks after this particular regimen.
- If high-dose Ara-C was part of prior treatment, documented time to progression must be at least 6 months after this particular regimen.
- Patients relapsed after autologous stem cell transplantation or not appropriate for myeloablative treatment.
- At least 1 measurable or assessable site of disease; in case of bone marrow infiltration only, bone marrow aspiration/ biospy is mandatory for all staging evaluations.
- age > 18 years
- ECOG/WHO Performance Score 0-2, unless lymphoma related.
- The following laboratory values at screening, unless lymphoma related:
- Absolute neutrophil count (ANC) >1500 cells/µL
- Platelets >100,000 cells/µL
- Transaminases (AST and ALT) <3 x upper limit of normal (ULN)
- Total bilirubin < 2 x ULN
- Creatinine <2 mg/dL or calculated creatinine clearance > 50 mL/min
- Toxic effects of previous therapy or surgery resolved to NCI CTC grade 2 or better.
- Premenopausal fertile females must agree to use a highly effective method of birth control for the duration of the therapy. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
- Written informed consent before performance of any study-related procedure.
- Men must agree not to father a child for the duration of therapy and must agree to advice a female partner to use a highly effective method of birth control
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:
- Treatment within another clinical trial within 30 days before trial entry or planed during this trial.
- Anti-neoplastic (including radiation and antibody treatment) or experimental therapy within 4 weeks before planed Day 1 of Cycle 1 (Nitrosoureas within 6 weeks ) or radioimmunoconjugates or toxin immunoconjugates such as Ibritumomab tiuxetan (Zevalin™) or Tositumomab (Bexxar®) within 12 weeks before Day 1 of Cycle 1.
- Known hypersensitivity to Rituximab, boron or mannitol.
- Active malignancy other than MCL within 5 years before Day 1 of Cycle 1, with the exception of complete resection of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy.
- Active systemic infection requiring treatment.
- HIV, hepatitis B or C
- Patient has > grade 2 peripheral sensory neuropathy or neuropathic pain defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE).
- Symptomatic degenerative or toxic encephalopathy.
- Serious medical condition (such as severe hepatic impairment, perdicardial disease, acute diffuse infiltrative pulmonary disease, systemic infections etc) or psychiatric illness likely to interfere with participation in this clinical study.
- Female subject is pregnant or breast-feeding (pregnancy testing is mandatory for premenopausal women).

Study & Design

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