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 January 2013 by The Lymphoma Academic Research Organisation
Sponsor:
The Lymphoma Academic Research Organisation
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT01582776
First received: April 20, 2012
Last updated: January 9, 2013
Last verified: January 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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:
MedlinePlus related topics:
Lymphoma
Drug Information available for:
Lenalidomide
U.S. FDA Resources
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: | September 2013 (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:
|
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)
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)
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 | |
| 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 | |
| Sub-Investigator: Cyrille Touzeau, 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 | |
| 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: | January 9, 2013 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
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 May 19, 2013