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

This study is currently recruiting participants.
Verified February 2014 by The Lymphoma Academic Research Organisation
Sponsor:
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT01582776
First received: April 20, 2012
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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 combiation in 2 separate populations: relapsed/refractory follicular lymphoma in one cohort and relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma) in the second cohort.


Condition Intervention Phase
Follicular Lymphoma Patients (Phase IB)
Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II)
Drug: Lenalidomide and GA101
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive (DLBCL and MCL) B-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by The Lymphoma Academic Research Organisation:

Primary Outcome Measures:
  • Determination of the recommended dose of lenalidomide in combination with fixed doses of GA101 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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.

  • PhaseII part: Overall Response Rate (CR+CRu+PR) after 6 cycles [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Response rates at the end of treatment including maintenance will be expressed as percentages with their 95% Exact Clopper Pearson Confidence Interval limits


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to 4.5 years ] [ Designated as safety issue: No ]

    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


  • Event Free survival [ Time Frame: Up to 4.5 years ] [ Designated as safety issue: No ]
    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.

  • Progression free survival [ Time Frame: Up to 4.5 years ] [ Designated as safety issue: No ]
    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.

  • Response duration [ Time Frame: Up to 4.5 years ] [ Designated as safety issue: No ]
    Patients alive and free of progression will be censored at their last follow-up date

  • Response rate at the end of maintenance treatment [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    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.

  • Complete response rate after induction [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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)).

  • Complete response rate after 3 cycles [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    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).



Estimated Enrollment: 200
Study Start Date: October 2012
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ga101 and lenalidomide
Ga101 and lenalidomide
Drug: Lenalidomide and GA101
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.
Other Names:
  • Revlimid
  • Obinutuzumab

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 follicular lymphoma in one cohort and relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma) in the second cohort. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  • Phase IB and II:
  • Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option
  • Aged 18 years or more
  • ECOG performance status 0, 1 or 2
  • 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.

Exclusion Criteria:

  • 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)
  • 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01582776

Contacts
Contact: Elise Hutasse, Project manager +334 72 66 93 33 elise.hutasse@gelarc.org
Contact: Yvain Robreau, Project manager +334 72 66 38 74 yvain.robreau@gelarc.org

Locations
France
Hôpital Henri Mondor Recruiting
Créteil, France, 94010
Contact: Corinne Haioun, PhD    +331 49 81 41 54      
Principal Investigator: Corinne Haioun, PhD         
Sub-Investigator: Karim Belhadj, MD         
Sub-Investigator: Jehan Dupuis, MD         
Sub-Investigator: Isabelle Gaillard, MD         
Sub-Investigator: Violaine Safar, MD         
Sub-Investigator: Cédric CLOZEL, MD         
Sub-Investigator: Taoufik EL GAOUI, MD         
Sub-Investigator: Catalina ENACHE, MD         
Sub-Investigator: Fabien LEBRAS, MD         
Sub-Investigator: Julien DEPAUS, MD         
CHRU de Lille Recruiting
Lille, France, 59037
Contact: Franck Morschhauser, MD    +33 20 44 42 90      
Sub-Investigator: Franck Morschhauser, MD         
Sub-Investigator: Louis Terriou, MD         
Sub-Investigator: Sabine Tricot, MD         
CHU St Eloi Recruiting
Montpellier, France, 34295
Contact: Guillaume Cartron, PhD         
Contact    +334 67 33 80 79      
Principal Investigator: Guillaume Cartron, PhD         
Sub-Investigator: Philippe Quittet, MD         
Sub-Investigator: Robert Navarro, MD         
CHU Hôtel Dieu Recruiting
Nantes, France, 44093
Contact: Steven Le Gouill, MD    +332 40 08 32 71      
Principal Investigator: Steven Le Gouill, MD         
Sub-Investigator: Nicolas Blin, MD         
Sub-Investigator: Aline Clavert, MD         
Sub-Investigator: Viviane Dubruille, MD         
Sub-Investigator: Thomas Gastinne, PhD         
Sub-Investigator: Béatrice Mahe, MD         
Sub-Investigator: Virginie Roland, MD         
Hôpital St Louis Recruiting
Paris, France, 75475
Contact: Catherine Thieblemont, PhD    +331 42 49 92 36      
Principal Investigator: Catherine Thieblemont, PhD         
Sub-Investigator: Pauline Brice, MD         
Sub-Investigator: Patricia FRANCHI-REZGUI, MD         
Sub-Investigator: Marie-Dominique Venon, MD         
Centre François Magendie Recruiting
Pessac, France, 33604
Contact: Kamal BOUABDALLAH, MD    +335 57 65 65 11      
Principal Investigator: Kamal BOUABDALLAH, MD         
Sub-Investigator: Marie-Sarah DILHUYDY, MD         
Sub-Investigator: Cédric Duclos, MD         
Sub-Investigator: Axelle Lascaux, MD         
Sub-Investigator: Noel Milpied, PhD         
CH Lyon Sud Recruiting
Pierre Bénite, France, 69495
Contact: Gilles Salles, PhD    +334 78 86 43 01      
Principal Investigator: Gilles Salles, PhD         
Sub-Investigator: Bertrand Coiffier, PhD         
Sub-Investigator: Fadhela BOUAFIA, MD         
Sub-Investigator: Daniel Espinouse, MD         
Sub-Investigator: Lionel Karlin, MD         
Sub-Investigator: Laure Lebras, MD         
Sub-Investigator: Anne-Sophie Michallet, MD         
Sub-Investigator: Catherine Traulle, MD         
Sub-Investigator: Marie BOUTELOUP, MD         
CHU Pontchaillou Recruiting
Rennes, France, 35003
Contact: Roch Houot, MD    +332 99 28 98 73      
Principal Investigator: Roch Houot, MD         
Sub-Investigator: Marc Bernard, MD         
Sub-Investigator: Charles Dauriax, MD         
Sub-Investigator: Sophie De Guibert, MD         
Sub-Investigator: Anne-Violaine Doncker, MD         
Sub-Investigator: Martine ESCOFFRE-BARBE, MD         
Sub-Investigator: Thierry Lamy, MD         
Sub-Investigator: Stanislas NIMUBONA, MD         
Centre henri Becquerel Recruiting
Rouen, France, 76038
Contact: Hervé Tilly, PhD    +332 32 08 22 02      
Sub-Investigator: Oana Brehar, MD         
Sub-Investigator: Fabrice Jardin, MD         
Sub-Investigator: Stephane Lepretre, MD         
Principal Investigator: Hervé Tilly, PhD         
Sub-Investigator: Aspasia STAMATOULLAS, MD         
Sub-Investigator: Pascal Lenain, MD         
Sub-Investigator: Nathalie Contentin, MD         
Sub-Investigator: Emilie Lemasle, MD         
Sub-Investigator: Nathalie Cardinael, MD         
Sub-Investigator: Marie-Laure Fontoura, MD         
Sub-Investigator: Carole Fronville, MD         
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Investigators
Principal Investigator: Franck MORSCHHAUSER, Professor Lymphoma Study Association
Principal Investigator: Roch HOUOT, Professor Lymphoma Study Association
  More Information

Additional Information:
No publications provided

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT01582776     History of Changes
Other Study ID Numbers: GALEN
Study First Received: April 20, 2012
Last Updated: February 12, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Ethics Committee - Université Catholique de Louvain

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014