Efficacy and Safety of Obinutuzumab Preemptive Treatment at the Time of the Molecular Relapse

NCT03229382 | Terminated Phase 2

• 2 other identifiers: ML291572015-005439-41
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is the evaluation of efficacy and safety of obinutuzumab preemptive treatment at the time of the molecular relapse after first line immunochemotherapy with autologous stem cell transplantation in mantle cell lymphoma patients.

Conditions

Mantle Cell Lymphoma

Keywords

MCL, obinutuzumab

Outcome Measures

Primary Outcomes (1)

• MRD negativity defined as a MRD level

  Molecular response rate (molRR) defined as a rate of molecular response with at least 10-4 sensitivity level assessed by quantitative RQ-PCR

  2 months after obinutuzumab treatment

Secondary Outcomes (7)

• Progression-free survival (PFS)

  3 years and 2 month

• Time to molecular relapse

  3 years and 2 month

• Overall survival (OS)

  3 years and 2 month

• Time to relapse/progression

  3 years and 2 month

• Event-free survival (EFS)

  3 years and 2 month

Study Arms (1)

Obinutuzumab 1000 mg IV infusion, day: 1, 8, 15, 22

EXPERIMENTAL

Patients with evidence of MCL molecular relapse defined as an increasing copy number in quantitative real-time polymerase chain reaction (RQ-PCR) of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes according to BIOMED-2 methodology and protocols in peripheral blood or/and bone marrow without evidence of clinical relapse/progression after auto-HCT procedure with all inclusion and no exclusion clinical trial criteria will receive 4 weekly infusions of obinutuzumab.

Drug: Obinutuzumab

Interventions

Obinutuzumab DRUG

Patients, in whom all inclusion criteria have been confirmed and all exclusion criteria have been ruled out, will receive 4 intravenous infusions of obinutuzumab (GA101, Gazyvaro) at a dose of 1000 mg on Days 1, 8, 15 and 22.

Also known as: Gazyvaro, GA101

Obinutuzumab 1000 mg IV infusion, day: 1, 8, 15, 22

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with evidence of MCL molecular relapse in peripheral blood or/and bone marrow,
• Diagnosis of mantle cell lymphoma confirmed by histopathology
• Presence of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion gene as a molecular marker used for minimal residual disease (MRD) assessment,
• Patients in CR/PR after first-line treatment with myeloablative consolidation and ASCT,
• Patients without evidence of mantle cell lymphoma progression/relapse according to the Lugano Classification criteria (2014),
• ECOG performance status ≤ 2,
• Signed patient's informed consent form,
• Survival prognosis \> 6 months,
• Women of childbearing potential must have a negative pregnancy test result prior to initiation of treatment with the study medication and must consent to undergo pregnancy tests during the treatment period.,
• Women of child-bearing potential must consent either to sexual abstinence or to using effective contraception (that results in a failure rate of \< 1% per year) while receiving the study medication and for 18 months after its discontinuation,
• Men must consent either to using an acceptable contraception method (that results in a failure rate of \< 1% per year) or continued sexual abstinence while receiving the study medication and for 6 months after its discontinuation.

You may not qualify if:

• Central nervous system involvement,
• Chemotherapy, radiation therapy or any other antineoplastic treatment (including steroids, monoclonal antibodies or medications at the stage of clinical studies, before receiving marketing authorisation) after ASCT and before administration of the study medication,
• Major surgery within 28 days prior to the study treatment initiation,
• Renal impairment (plasma creatinine concentration \> 1.5 × upper limit of normal and/or creatinine clearance ≤ 40 ml/h),
• Hepatic impairment (total bilirubin concentration \> 1.5 × upper limit of normal, AST and ALT \> 2.5 × upper limit of normal),
• Hb\< 9 g/dl, ANC \< 1.5 G/l, platelets \< 75 G/l,
• International normalized ratio (INR) \> 1.5,
• Clinically significant heart disease, including uncontrolled arrhythmias, unstable coronary artery disease, serious congestive circulatory failure (NYHA III-IV), myocardial infarction within 6 months before enrolment,
• Other comorbidities, not responding to treatment, including, but not limited to: hematopoietic system diseases, gastrointestinal system diseases, endocrine system diseases, respiratory system diseases, neurological diseases, cerebral diseases and mental diseases that could affect compliance with the protocol or interpretation of results,
• Active infections (viral, bacterial, fungal),
• Coexistence of another neoplasm or a history of neoplastic disease (except for adequately treated basal cell carcinoma or squamous cell skin carcinoma, in situ cervical cancer or other neoplasm if the patient is in complete remission after at least 5 years of treatment discontinuation),
• Active HIV, HBV or HCV infection,
• Positive testing for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing). Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA,
• Vaccination with live vaccines within 28 days prior to start of the preemptive treatment,
• Known or suspected hypersensitivity to the study medication,

Sponsors & Collaborators

• Polish Lymphoma Research Group: lead
• Roche Pharma AG: collaborator

Study Sites (1)

Centrum Onkologii - Instytut im. Marii Skłodowskiej- Curie Klinika Nowotworów Układu Chłonnego

Warsaw, 02-781, Poland

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Michał Szymczyk, MD

  Institute of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 25, 2017
• Study Start: May 14, 2018
• Primary Completion: January 31, 2020
• Study Completion: January 31, 2020
• Last Updated: August 16, 2023

Record last verified: 2023-08

Locations

PL (1)