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Follicular LymphomaPhase 2Alternative-CNCT05387616

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

A Phase 2 study testing Copanlisib and Obinutuzumab in people with Follicular Lymphoma, run by Ludwig-Maximilians - University of Munich at 40 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Copanlisib and Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
40 sitesGermany
Study dates
19 Oct 2020to 19 May 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

Germany40 sites

  • Gesundheitszentrum St. Marien GmbH

    Amberg, 92224

  • HELIOS Klinikum Bad Saarow

    Bad Saarow, 15526

  • Vivantes Netzwerk für Gesundheit GmbH - Vivantes Klinikum am Urban

    Berlin, 10967

  • Charité Campus Benjamin Franklin

    Berlin, 12200

  • Universitätsklinikum Bonn

    Bonn, 53127

  • Klinikum Chemnitz gGmbH

    Chemnitz, 09113

  • Carl-Thiem-Klinikum Cottbus gGmbH

    Cottbus, 03048

  • Cancer Center Dachau

    Dachau, 85221

  • Städtisches Klinikum Dessau

    Dessau, 06847

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

    Dresden, 01307

  • Marien Hospital Düsseldorf

    Düsseldorf, 40479

  • Universitätsklinikum Essen

    Essen, 45147

  • Centrum für Hämatologie und Onkologie Bethanien

    Frankfurt am Main, 60389

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Universitätsklinikum Jena

    Jena, 07747

  • Klinikum Kassel

    Kassel, 34125

  • Universitätsklinikum Schleswig-Holstein

    Kiel, 24105

  • Praxis für Hämatologie und Onkologie

    Koblenz, 56068

  • Klinikum der Stadt Ludwigshafen gGmbH

    Ludwigshafen, 67063

  • Schwerpunktpraxis für Hämatologie und Onkologie

    Magdeburg, 39104

  • Universitätsklinikum Magdeburg A.ö.R.

    Magdeburg, 39120

  • Universitätsklinik Mannheim

    Mannheim, 68167

  • Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus

    Mönchengladbach, 41063

  • LMU Klinikum

    München, Bavaria, 81377

  • Klinikum rechts der Isar der TU München

    München, 81675

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Münster, 48149

  • Universitätsklinikum Münster

    Münster, 48149

  • Stauferklinikum Schwäbisch Gmünd

    Mutlangen, 73557

  • Friedrich Ebert Krankenhaus

    Neumünster, 24534

  • Rheinland Klinikum, Lukaskrankenhaus Neuss

    Neuss, 41464

  • Brüderkrankenhaus St. Josef Paderborn

    Paderborn, 33098

  • Universitätsmedizin Rostock

    Rostock, 18057

  • Klinikum Südstadt Rostock

    Rostock, 18059

  • Gemeinschaftspraxis Dr. med. G.A. Jacobs

    Saarbrücken, 66111

  • Klinikum Mutterhaus der Borromäerinnen gGmbH

    Trier, 54290

  • Universitätsklinikum Tübingen

    Tübingen, 72076

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Petrus Kankenhaus

    Wuppertal, 42283

  • Hämatologisch-Onkologische Schwerpunktpraxis

    Würzburg, 97080

Other trials in Germany

About this study

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.

Being tested
Copanlisib, Obinutuzumab
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CopanlisibDrug

    Also called ALIQOPA™

    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.

  • ObinutuzumabDrug

    Also called GAZYVARO®

    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.

Study groups in NCT05387616
Study groupRoleWhat they receive
Copanlisib + ObinutuzumabExperimentalNot described
Receives: Drug: Copanlisib; Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. One-year progression-free survival (PFS) probability from study registration

    The rate of patients achieving a progression free survival of more than one year after registration (one-year PFS rate) will serve as early readout for efficacy.

    Measured: 1 year

Secondary outcomes (14)

  1. Complete remission (CR) rates and overall response (CR or partial remission, PR) rates

    Measured: at end of induction (month 6), at end of consolidation (month 12), and at end of maintenance (month 30)

  2. Progression free survival from registration

    Measured: continuous observation up to 78 months

  3. Duration of response

    Measured: from end of induction to progression or death assessed up to 72 months

  4. Cumulative incidence of progression

    Measured: from registration to end of study assessed up to 78 months

  5. Failure-free survival

    event defined by failure to achieve a CR/PR after 6 months or progression after CR or PR or death from any cause

    Measured: from start of therapy assessed up to 78 months

  6. Time to next anti-lymphoma therapy and time to next chemotherapy based treatment

    Measured: from start of first-line therapy up to 78 months

  7. Overall survival

    Measured: from registration up to 78 months

  8. Treatment associated adverse events

    Measured: continuous observation up to 78 months

  9. Percentage of MRD-negative patients

    Measured: therapy (month 12), and at end maintenance therapy (month 30)

  10. Duration of molecular remission for MRD negative patients

    Measured: from end of induction therapy up to 72 months

  11. Cumulative incidence of secondary transformations to aggressive lymphoma

    Measured: ongoing observation up to 78 months

  12. Cumulative incidence of secondary malignancies

    Measured: ongoing observation up to 78 months

  13. Percentage of patients with compliance to therapy

    Measured: after 6, 12, and 30 months

  14. Frequency of patient-reported lymphoma symptoms and concerns (FACT-Lym)

    Measured: Baseline, End of Induction, End of Consolidation, End of Maintenance, and every 6 months during FU for at least 2 years until end of the whole study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2022
  2. Study start19 Oct 2020
  3. Primary completion16 Sep 2023
  4. Study completion19 May 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05387616
Sponsor's protocol ID
Alternative-C
Other IDs
2018-004038-13, 2018
Acronym
Alternative-C
Status last verified
Mar 2024
First submitted
27 Jan 2022
Last updated
12 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Copanlisib and Obinutuzumab in people with Follicular Lymphoma, run by Ludwig-Maximilians - University of Munich at 40 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

One-year progression-free survival (PFS) probability from study registration (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05387616.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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