A Prospective Multicenter Phase 2 Study of the Chemotherapy-Free Combination of the Intravenous Phosphatidylinositol-3-Kinase (PI3K) Inhibitor Copanlisib in Combination With Obinutuzumab in Patients With Previously Untreated Follicular Lymphoma (FL) and a High Tumor Burden

NCT ID: NCT05387616

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-19
• Study Completion Date: 2026-05-19

Brief Summary

The Alternative-C Trial is a prospective, multicenter Phase 2 Study to evaluate the efficacy of the chemotherapy-free combination of copanlisib and obinutuzumab in patients with previously untreated follicular lymphoma (FL) and a high tumor burden. Additionally, the combination should be evaluated in terms of secondary efficacy endpoints, treatment compliance, safety and patient-reported symptoms. The study Population includes Patients > 18 years of age with histologically confirmed follicular lymphoma grade 1, 2 or 3A with Ann Arbor Stage III/IV or stage II not suitable for radiotherapy and in need of therapy.

Conditions

Follicular Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Copanlisib + Obinutuzumab

Group Type: EXPERIMENTAL

Copanlisib

Intervention Type: DRUG

Induction therapy will comprise 6 cycles of copanlisib, administered by intravenous Infusion at a dose of 60 mg on day 1,8,15 of cycles 1-6 to be given every 28 days.

Consolidation therapy will comprise another 24 weeks of copanlisib in patients with clinical Remission 28 days after the last induction cycle. It will be administered by intravenous Infusion at a dose of 60 mg on days 1 and 15 of cycles 7 - 12 to be given every 28 days.

Maintenance therapy will comprise another 72 weeks of copanlisib in patients with clinical remissions 28 days after the last consolidation cycle.

Obinutuzumab

Intervention Type: DRUG

Induction therapy will comprise 6 cycles of obinutuzumab, administered by intravenous infusion at a dose of 1000 mg on days 1,8, 15 of cycle 1 and on day 1 of cycles 2 - 6 to be given every 28 days.

Consolidation therapy will comprise of another 24 weeks of obinutuzumab in patients with clinical remission 28 days after the last induction cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks.

Maintenance therapy will comprise another 72 weeks in patients with clinical remission 28 days after the last consolidation cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks.

Interventions

Copanlisib

Induction therapy will comprise 6 cycles of copanlisib, administered by intravenous Infusion at a dose of 60 mg on day 1,8,15 of cycles 1-6 to be given every 28 days.

Consolidation therapy will comprise another 24 weeks of copanlisib in patients with clinical Remission 28 days after the last induction cycle. It will be administered by intravenous Infusion at a dose of 60 mg on days 1 and 15 of cycles 7 - 12 to be given every 28 days.

Maintenance therapy will comprise another 72 weeks of copanlisib in patients with clinical remissions 28 days after the last consolidation cycle.

Intervention Type: DRUG

Obinutuzumab

Induction therapy will comprise 6 cycles of obinutuzumab, administered by intravenous infusion at a dose of 1000 mg on days 1,8, 15 of cycle 1 and on day 1 of cycles 2 - 6 to be given every 28 days.

Consolidation therapy will comprise of another 24 weeks of obinutuzumab in patients with clinical remission 28 days after the last induction cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks.

Maintenance therapy will comprise another 72 weeks in patients with clinical remission 28 days after the last consolidation cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks.

Intervention Type: DRUG

Other Intervention Names

ALIQOPA™; GAZYVARO®

Eligibility Criteria

Inclusion Criteria

• Subjects will only be included in the study, if they meet all of the following criteria:
• Histologically confirmed follicular lymphoma grade 1, 2 or 3A with a biopsy performed within 12 months before study entry and with material available for central review and complementary scientific analyses
• Ann Arbor stage III/IV, or stage II not suitable for radiotherapy, or stage II bulky disease
• Age ≥ 18 years
• No prior lymphoma therapy
• Need for start of therapy as defined by at least one of the following criteria:

• bulky disease at study entry according to the GELF criteria (nodal or extranodal mass > 7 cm in its greatest diameter)
• B symptoms (fever, drenching night sweats, or unintentional weight loss of > 10% of normal body weight over a period of 6 months or less)
• hematopoietic insufficiency (granulocytopenia < 1500/µl, Hb < 10 g/dl, thrombocytopenia < 100000/µl)
• compressive syndrome or high risk for compression syndrome
• pleural/peritoneal effusion
• symptomatic extranodal manifestations
• At least one bi-dimensionally measurable lesion (> 2 cm in its largest dimension by CT scan or MRI)
• Performance status ≤ 2 on the ECOG scale
• Adequate hematologic function (unless abnormalities are related to NHL), defined as follows:

• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1500/µl
• Platelet count ≥ 75000/µl
• Women are not breast feeding, are using highly effective contraception (see section 11.4.1), are not pregnant, and agree not to become pregnant during participation in the study and during the 18 months thereafter (pregnancy testing is mandatory for premenopausal women).
• Men agree not to father a child during participation in the study and during the 18 months thereafter.
• Written informed consent

Exclusion Criteria

Subjects will not be included in the study if any of the following criteria apply:

• Transformation to high-grade lymphoma (secondary to "low grade" FL)
• Grade 3B follicular lymphoma
• Presence or history of CNS disease (either CNS lymphoma or leptomeningeal lymphoma)
• Known hypersensitivity to any of the study drugs
• Known sensitivity to murine products
• Patients with HbA1c > 8.5 % at Screening
• Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment)
• Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 20 mg/day prednisone or administered as prephase treatment according to study protocol (see section 7.2 of study protocol)
• Concomitant use of strong CYP3A4 inhibitors and/or inducers
• Prior or concomitant malignancies except:

• non-melanoma skin cancer or adequately treated in carcinoma in situ of the cervix
• other malignant diseases not specified above which have been curatively treated by surgery alone and from which subject is disease-free for ≥ 5 years without further treatment
• Serious disease interfering with a regular therapy according to the study protocol:

• 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
• pulmonary (e.g. chronic lung disease with hypoxemia)
• endocrine (e.g. 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 caused by known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome])
• Positive test results for chronic HBV infection (defined as positive HBsAg serology) 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 or prior but cured hepatitis B are eligible.

• Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing) Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
• Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
• Known history of HIV seropositive status
• Patients with a history of confirmed PML
• Vaccination with a live vaccine within 28 days prior to registration
• Recent major surgery (within 4 weeks prior to the start of Cycle 1)
• History of stroke or intracranial hemorrhage within 6 months prior to registration
• Serious underlying medical conditions, which could impair the ability of the patient to undergo the treatment offered in the study (e.g. ongoing infection, gastric ulcers, active autoimmune disease)
• Treatment within another clinical study within 30 days prior to study entry
• Prior organ, bone marrow, or peripheral blood stem cell transplantation
• Known or persistent abuse of medication, drugs, or alcohol
• Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Christian Schmidt, MD

Dr. Christian Schmidt

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian Schmidt, Dr.

Role: PRINCIPAL_INVESTIGATOR

LMU Klinikum, Medical department III

Locations

LMU Klinikum

München, Bavaria, Germany

Gesundheitszentrum St. Marien GmbH

Amberg, , Germany

HELIOS Klinikum Bad Saarow

Bad Saarow, , Germany

Vivantes Netzwerk für Gesundheit GmbH - Vivantes Klinikum am Urban

Berlin, , Germany

Charité Campus Benjamin Franklin

Berlin, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Carl-Thiem-Klinikum Cottbus gGmbH

Cottbus, , Germany

Cancer Center Dachau

Dachau, , Germany

Städtisches Klinikum Dessau

Dessau, , Germany

Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex

Dresden, , Germany

Marien Hospital Düsseldorf

Düsseldorf, , Germany

Universitätsklinikum Essen

Essen, , Germany

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt am Main, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Jena

Jena, , Germany

Klinikum Kassel

Kassel, , Germany

Universitätsklinikum Schleswig-Holstein

Kiel, , Germany

Praxis für Hämatologie und Onkologie

Koblenz, , Germany

Klinikum der Stadt Ludwigshafen gGmbH

Ludwigshafen, , Germany

Schwerpunktpraxis für Hämatologie und Onkologie

Magdeburg, , Germany

Universitätsklinikum Magdeburg A.ö.R.

Magdeburg, , Germany

Universitätsklinik Mannheim

Mannheim, , Germany

Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus

Mönchengladbach, , Germany

Stauferklinikum Schwäbisch Gmünd

Mutlangen, , Germany

Klinikum rechts der Isar der TU München

München, , Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, , Germany

Universitätsklinikum Münster

Münster, , Germany

Friedrich Ebert Krankenhaus

Neumünster, , Germany

Rheinland Klinikum, Lukaskrankenhaus Neuss

Neuss, , Germany

Brüderkrankenhaus St. Josef Paderborn

Paderborn, , Germany

Universitätsmedizin Rostock

Rostock, , Germany

Klinikum Südstadt Rostock

Rostock, , Germany

Gemeinschaftspraxis Dr. med. G.A. Jacobs

Saarbrücken, , Germany

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Petrus Kankenhaus

Wuppertal, , Germany

Hämatologisch-Onkologische Schwerpunktpraxis

Würzburg, , Germany

Countries

Germany

Other Identifiers

2018-004038-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Alternative-C

Identifier Type: -

Identifier Source: org_study_id