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Follicular Lymphoma Patients (Phase IB)Phase 1/2NCT01582776

Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive B-cell Lymphoma

A Phase 1/2 study testing Lenalidomide and GA101 in people with Follicular Lymphoma Patients (Phase IB) and Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II), run by The Lymphoma Academic Research Organisation at 25 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is to determine first the appropriate dose of lenalidomide to administer in combination with fixed doses of obinutuzumab in relapsed/refractory follicular lymphoma patients. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lenalidomide and GA101
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
317 participants
Where
25 sitesin 2 countries
Study dates
3 Oct 2012to 20 May 2022
Phase
Phase 1/2
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

  • Phase IB only: Histologically documented CD20-positive follicular lymphoma (WHO grade 1, 2, or 3a) patients
  • Phase II: Patients with either histologically documented CD20-positive Diffuse large-cell lymphoma or Mantle cell lymphoma (cohort 1) or follicular lymphoma, WHO grade 1, 2 or 3a (cohort 2-3-4)
  • Phase IB and II:
  • Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option (cohort 2 only)
  • Aged 18 years or more
  • ECOG performance status 0, 1 or 2
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  • At least one bi-dimensionally measurable nodal or tumor lesion defined by CT scan as: greatest transverse diameter > 1.5 cm and a short axis ≥ 10mm
  • Signed inform consent
  • Life expectancy ≥ 3 months.
  • All subjects must be able to understand and fulfill the lenalidomide Pregnancy Prevention Plan requirements (see in appendix)
  • Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 2 months after discontinuation of all study treatments.

Who cannot join

  • Previous treatment with obinutuzumab or lenalidomide
  • Known CD20 negative status at relapse/progression. Biopsy at relapse/progression is recommended but not mandatory
  • Central nervous system or meningeal involvement by lymphoma
  • Contraindication to any drug contained in the study treatment regimen
  • Known HIV or HTLV-1 infection, positive serology to HB surface antigen [HBsAg] or total HB core antibody [anti-HB-c]) and Hepatitis C (Hepatitis C virus [HCV] antibody)
  • Any serious active disease or co-morbid medical condition (such as New York Heart Association Class II or IV cardiac disease, severe arrhythmia, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm or other according to investigator's decision)
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  • Any of the following laboratory abnormalities unless secondary to underlying lymphoma:
  • Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L).
  • Platelet count < 100,000/mm3 (100 x 109/L) unless due to lymphoma for phase II part.
  • Serum SGOT/AST or SGPT/ALT 3.0 x upper limit of normal (ULN) unless disease involvement.
  • Serum total bilirubin > 2.0 mg/dL (34 μmol/L), except if disease related or in case of Gilbert syndrome
  • Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 50 mL /min. For phase II part of the study, patients with calculated creatinine clearance between 30 and 50ml/min can be included and lenalidomide dose will be adjusted as follows (10mg once daily)
  • Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 5 years
  • Any serious medical condition, laboratory abnormality (other than mentioned above), or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or lactating females.
  • Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide.
  • Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.
  • Subjects with ≥ Grade 2 neuropathy.
  • Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy
  • Patients taking corticosteroids during 4 weeks before inclusion, unless administered at a dose equivalent to ≤ 10 mg/day prednisone (over these 4 weeks)
  • Prior history of Progressive Multifocal Leukoencephalopathy (PML)

Trial locations and contacts

25 sites in 2 countries.

25 sites in 2 countries

France18 sites

  • CHU d'Amiens

    Amiens, 80054

  • Institut Bergonié

    Bordeaux, 33076

  • Institut d'Hématologie de Basse Normandie

    Caen, 14076

  • CHU d'Estaing

    Clermont-Ferrand, 63000

  • Hôpital Henri Mondor

    Créteil, 94010

  • CHU de Dijon

    Dijon, 21034

  • CHU de Grenoble

    Grenoble, 38043

  • CHRU de Lille

    Lille, 59037

  • Centre Léon Bérard

    Lyon, 69373

  • Institut Paoli Calmette

    Marseille, 13273

  • CHU St Eloi

    Montpellier, 34295

  • CHU Brabois

    Nancy, 54511

  • CHU Hôtel Dieu

    Nantes, 44093

  • Hôpital St Louis

    Paris, 75475

  • Centre François Magendie

    Pessac, 33604

  • CH Lyon Sud

    Pierre-Bénite, 69495

  • CHU Pontchaillou

    Rennes, 35003

  • Centre henri Becquerel

    Rouen, 76038

Other trials in France

Belgium7 sites

  • ZNA Stuivenberg

    Antwerp, 2060

  • A.Z. Sint Jan AV

    Bruges, 8000

  • institut Jules Bordet

    Brussels, 1000

  • Université Catholique de Louvain Saint Luc

    Brussels, 1200

  • AZ Groeninge - Campus Maria's Voorzienigheid

    Kortrijk, 8500

  • CHU de Liège

    Liège, 4000

  • Université Catholique de Louvain Mont Godinne

    Yvoir, 5530

Other trials in Belgium

About this study

Official title: A Phase Ib/II Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Follicular and Relapsed/Refractory Aggressive (DLBCL and MCL) B-cell Lymphoma

This study is to determine first the appropriate dose of lenalidomide to administer in combination with fixed doses of obinutuzumab in relapsed/refractory follicular lymphoma patients.

In a second step, this study aims to determine the efficacy of this combination in 3 separate populations: relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma: cohort 1), relapsed/refractory follicular lymphoma (cohort 2) and previously untreated follicular lymphoma (cohorts 3 and 4).

Read the detailed description

This study is an open label, multicenter study with two phases:

The Phase IB part of the study is a dose escalation study of lenalidomide (Revlimid) administered orally during on 3 weeks of every 28-day cycle, in combination with fixed doses of obinutuzumab (GA101) in relapsed/refractory follicular lymphoma patients.

The Phase II part of the study is an efficacy study of the association of the recommended dose of lenalidomide associated with GA101 in 2 separate populations of patients: relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma: cohort 1), relapsed/refractory follicular lymphoma (cohort 2) and previously untreated follicular lymphoma (cohorts 3 and 4). First, all patients will receive a combination of obinutuzumab and lenalidomide for a total of 6 cycles. Patients who achieve at least a partial response after 6 cycles will receive a maintenance treatment with obinutuzumab for 2 years and Lenalidomide for 1 year as tolerated, or until disease progression.

Being tested
Lenalidomide and GA101

What participants receive

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

  • Lenalidomide and GA101Drug

    Also called Revlimid, Obinutuzumab

    1000mg of GA101 on D8, D15 and D22of cycle 1 and on D1 of cycles 2 to 6. Oral lenalidomide once daily at 10/15/20/25mg (phase I part) or at recommended dose (phase II part) on days 1 to 21 of a 28-day cycle for the first cycle and on days 2 to 22 of a 28-day cycle for cycles 2 to 6.

Study groups in NCT01582776
Study groupRoleWhat they receive
Lenalidomide and GA101ExperimentalGa101 and lenalidomide
Receives: Drug: Lenalidomide and GA101

What is being measured

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

  1. Phase I part: Determination of the recommended dose of lenalidomide in combination with fixed doses of GA101

    The determination of the recommended dose of lenalidomide in combination with fixed doses of GA101 will be performed by a dose escalation approach. Dose Limiting Toxicities (DLTs) observed during the administration of the first 2 cycles of the study will be listed for each escalation step.

    Measured: 28 days

  2. Phase II part: Overall Response Rate (CR+CRu+PR) after 6 cycles

    Response rates at the end of treatment including maintenance will be expressed as percentages with their 95% Exact Clopper Pearson Confidence Interval limits

    Measured: 24 weeks

Secondary outcomes (7)

  1. Overall survival (OS)

    Overall survival will be measured from the date of inclusion to the date of death from any cause.

    Alive patients will be censored at their last date known to be alive

    Measured: Up to 4.5 years

  2. Event Free survival

    Event-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause.

    Measured: Up to 4.5 years

  3. Progression free survival

    Progression-Free Survival will be measured according to the Cheson 2007 criteria. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.

    Measured: Up to 4.5 years

  4. Response duration

    Patients alive and free of progression will be censored at their last follow-up date

    Measured: Up to 4.5 years

  5. Response rate at the end of maintenance treatment

    Response rates will be evaluated at the end of maintenance phase for patients who achieve a CR/PR after induction treatment and received at least one dose of maintenance. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 2007)). Patient without response assessment after maintenance treatment (due to whatever reason) will be considered as non-responder.

    Measured: 2.5 years

  6. Complete response rate after induction

    Disease response evaluation after 6 cycles will be used to determine the Complete Response Rate. Response after 6 cycles will be assessed only if patient completes induction phase. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999 and 2007)).

    Measured: 24 weeks

  7. Complete response rate after 3 cycles

    Disease response evaluation after 3 cycles will be used to determine the Complete Response Rate.

    Response after 3 cycles will be assessed at the end of completion of the 3 cycles if patient received all 3 cycles or at withdrawal. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999 and 2007).

    Measured: 12 weeks

Timeline

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

  1. First posted23 Apr 2012 (estimated)
  2. Study start3 Oct 2012
  3. Primary completion11 Jul 2018
  4. Study completion20 May 2022

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
317 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01582776
Sponsor's protocol ID
GALEN
Status last verified
Mar 2023
First submitted
20 Apr 2012
Last updated
17 Mar 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Bachy E, Houot R, Feugier P, Bouabdallah K, Bouabdallah R, Virelizier EN, Maerevoet M, Fruchart C, Snauwaert S, Le Gouill S, Marolleau JP, Molina L, Molucon-Chabrot C, Thieblemont C, Tilly H, Bijou F, Haioun C, Van den Neste E, Fabiani B, Meignan M, Cartron G, Salles G, Casasnovas O, Morschhauser F. Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study. Blood. 2022 Apr 14;139(15):2338-2346. doi: 10.1182/blood.2021013526.

    PubMed 34936697

  • Morschhauser F, Le Gouill S, Feugier P, Bailly S, Nicolas-Virelizier E, Bijou F, Salles GA, Tilly H, Fruchart C, Van Eygen K, Snauwaert S, Bonnet C, Haioun C, Thieblemont C, Bouabdallah R, Wu KL, Canioni D, Meignin V, Cartron G, Houot R. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Lancet Haematol. 2019 Aug;6(8):e429-e437. doi: 10.1016/S2352-3026(19)30089-4. Epub 2019 Jul 8.

    PubMed 31296423

  • Morschhauser F, Salles G, Le Gouill S, Tilly H, Thieblemont C, Bouabdallah K, Fabiani B, Menard C, Tarte K, Cartron G, Houot R. An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma. Blood. 2018 Oct 4;132(14):1486-1494. doi: 10.1182/blood-2018-05-853499. Epub 2018 Aug 1.

    PubMed 30068505

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lenalidomide and GA101 in people with Follicular Lymphoma Patients (Phase IB) and Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II), run by The Lymphoma Academic Research Organisation at 25 sites in 2 countries.

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 11 inclusion and 21 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: finished, as of the sponsor's last update on 17 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in France, Belgium. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Phase I part: Determination of the recommended dose of lenalidomide in combination with fixed doses of GA101 (time frame: 28 days). The study lists 2 primary outcomes in all. 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 NCT01582776, which also lists 3 linked publications.

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 17 Mar 2023.

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