Informations générales (source: ClinicalTrials.gov)
LOC-R01: Randomized Phase IB/II Study of Escalating Doses of Lenalidomide and Ibrutinib in Association With R-MPV as a Targeted Induction Treatment for Patients Aged 18 to 60 (up to 65 for Phase II) With a Newly Diagnosed Primary Central Nervous System Lymphoma (LOC-R01)
Interventional
Phase 1/Phase 2
Institut Curie (Voir sur ClinicalTrials)
octobre 2020
février 2035
30 juillet 2024
This study is to improve the first-line induction chemotherapy, by combining either
Ibrutinib, or Lenalidomide, to a conventional immuno- chemotherapy of R-MPV type
(Rituximab-Methotrexate-Procarbazine-Vincristine). This is a randomized Phase II trial,
preceded by a dose escalation phase Ib. The objective of the phase Ib is to rule out any
limiting toxicity of the new treatment associations, and to determine the recommended
dose of Lenalidomide and Ibrutinib to be used in the phase II. In the phase II study,
patients will receive 4 cycles of R-MPV + Lenalidomide or 4 cycles of R-MPV + Ibrutinib.
The therapeutic response will be evaluated after the 2nd and the 4th cycle. Patients in
good therapeutic response will proceed to the consolidation phase with Autologous Stem
Cell Transplantation (ASCT).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:31 | Contact (sur clinicalTrials) | |||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Cochin | Lise WILLEMS, MD | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Henri Becquerel - 76000 - Rouen - France | Fabrice JARDIN, PhD | Contact (sur clinicalTrials) | |||
| Centre Lacassagne - Nice - France | Frédéric PEYRADE, MD | Contact (sur clinicalTrials) | |||
| CH Colmar - Colmar - France | Guido AHLE, MD | Contact (sur clinicalTrials) | |||
| CHU Clermont-Ferrand - Clermont-Ferrand - France | Cécile MOLUCON-CHABROT, MD | Contact (sur clinicalTrials) | |||
| CHU Dijon - Dijon - France | Contact (sur clinicalTrials) | ||||
| CHU Poitiers - Poitiers - France | Vincent DELWAIL, MD | Contact (sur clinicalTrials) | |||
| CHU Rennes - 35000 - Rennes - France | Thierry LAMY De La CHAPELLE, PhD | Contact (sur clinicalTrials) | |||
| CHU Tours - Tours - France | Emmanuel GYAN, MD | Contact (sur clinicalTrials) | |||
| Institut Bergonié - Bordeaux - France | Anna SCHMITT, MD | Contact (sur clinicalTrials) | |||
| IUCT -Oncopole - Toulouse - France | Lucie Obéric, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CH côte Basque - 64100 - Bayonne - France | Sophie BERNARD, MD | Contact (sur clinicalTrials) | |||
| CHRU Lille - 69000 - Lille - France | Franck MORSCHHAUSER, PhD | Contact (sur clinicalTrials) | |||
| CHU Amiens - Amiens - France | Caroline DELETTE, MD | Contact (sur clinicalTrials) | |||
| CHU Angers - Angers - France | Jérôme PAILLASSA, MD | Contact (sur clinicalTrials) | |||
| CHU Besançon - Besançon - France | Adrien CHAUCHET, MD | Contact (sur clinicalTrials) | |||
| CHU Caen - Caen - France | Gandhi DAMAJ, MD | Contact (sur clinicalTrials) | |||
| CHU Créteil - Créteil - France | Louise ROULIN, MD | Contact (sur clinicalTrials) | |||
| CHU Grenoble - Grenoble - France | Rémy Rémy GRESSIN, MD | Contact (sur clinicalTrials) | |||
| CHU La Timone Marseille - Marseille - France | Olivier CHINOT, MD | Contact (sur clinicalTrials) | |||
| CHU Limoges - Limoges - France | Julie ABRAHAM, MD | Contact (sur clinicalTrials) | |||
| CHU Lyon - Lyon - France | Hervé GHESQUIERES, MD | Contact (sur clinicalTrials) | |||
| CHU Nancy - Nancy - France | Luc TAILLANDIER, PhD | Contact (sur clinicalTrials) | |||
| CHU Nantes - Nantes - France | Thomas GASTINNE, MD | Contact (sur clinicalTrials) | |||
| CHU Nîmes - Carémeau - 30029 - Nîmes - France | Agathe WAULTIER-RASCALOU, MD | Contact (sur clinicalTrials) | |||
| CHU Pitié-Salpêtrière - 75013 - Paris - France | Caroline HOUILLIER, MD | Contact (sur clinicalTrials) | |||
| institut de Cancérologie de Strasbourg - 67033 - Strasbourg - France | Luc-Mathieu FORNECKER, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Newly diagnosed Primary Central Nervous System Lymphoma (PCNSL).
2. a) Aged between 18 and 60 (>18 and < 60) - phase IB b) Aged between 18 and 65 (≥ 18
and ≤ 65) - phase II.
3. Histological confirmed diagnosis of Primary central nervous system lymphoma of
Diffuse Large B-Cell Lymphomas (DLBCL) type OR patients with a measurable typical
cerebral lesion on MRI with a diagnosis made by cytology and/or by flow cytometry on
the vitreous or on the cerebral spinal fluid.
4. Measurable lesion on MRI with gadolinium enhancement.
5. Adequate hematological, renal and hepatic function (Laboratory Parameters realized
within 14 days before inclusion):
1. Absolute neutrophil count (ANC) >1000/mm3
2. Platelets > 100,000/mm3 independent of transfusion support
3. Alanine aminotransferase and aspartate aminotransferase ≤ 3 x Upper Limit of
Normal (ULN)
4. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome
or of non-hepatic origin
5. Estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73m2.
6. Able to swallow capsules.
7. Karnofsky performance status: 40-100% for the phase IB and no restriction on the KPS
for the phase II.
8. Able to understand teratogenic risks of the Lenalidomide and Ibrutinib. Patient must
be able to understand and fulfill the Lenalidomide Pregnancy Prevention Plan
requirements. This plan may be accepted by the person of confidence in case of
impaired cognitive status of the patient.
9. Women of childbearing potential (WCBP)* and men who are sexually active must be
practicing a highly effective method** of birth control. Women should avoid a
pregnancy while taking treatment by Lenalidomide or Ibrutinib and for up to 1 month
after ending treatment. Men must agree to not to father a child or donate sperm
during treatment by Lenalidomide or Ibrutinib and up to 3 months after the last dose
of study drug.
10. Women of childbearing potential (WCBP)* must have a negative serum (beta-human
chorionic gonadotropin [B-hCG]) or urine pregnancy test at inclusion.
11. Signed informed consent, which could be signed by a person on confidence in case the
neurologic status of the patient does not allow him to understand and/or to sign.
1. Newly diagnosed Primary Central Nervous System Lymphoma (PCNSL).
2. a) Aged between 18 and 60 (>18 and < 60) - phase IB b) Aged between 18 and 65 (≥ 18
and ≤ 65) - phase II.
3. Histological confirmed diagnosis of Primary central nervous system lymphoma of
Diffuse Large B-Cell Lymphomas (DLBCL) type OR patients with a measurable typical
cerebral lesion on MRI with a diagnosis made by cytology and/or by flow cytometry on
the vitreous or on the cerebral spinal fluid.
4. Measurable lesion on MRI with gadolinium enhancement.
5. Adequate hematological, renal and hepatic function (Laboratory Parameters realized
within 14 days before inclusion):
1. Absolute neutrophil count (ANC) >1000/mm3
2. Platelets > 100,000/mm3 independent of transfusion support
3. Alanine aminotransferase and aspartate aminotransferase ≤ 3 x Upper Limit of
Normal (ULN)
4. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome
or of non-hepatic origin
5. Estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73m2.
6. Able to swallow capsules.
7. Karnofsky performance status: 40-100% for the phase IB and no restriction on the KPS
for the phase II.
8. Able to understand teratogenic risks of the Lenalidomide and Ibrutinib. Patient must
be able to understand and fulfill the Lenalidomide Pregnancy Prevention Plan
requirements. This plan may be accepted by the person of confidence in case of
impaired cognitive status of the patient.
9. Women of childbearing potential (WCBP)* and men who are sexually active must be
practicing a highly effective method** of birth control. Women should avoid a
pregnancy while taking treatment by Lenalidomide or Ibrutinib and for up to 1 month
after ending treatment. Men must agree to not to father a child or donate sperm
during treatment by Lenalidomide or Ibrutinib and up to 3 months after the last dose
of study drug.
10. Women of childbearing potential (WCBP)* must have a negative serum (beta-human
chorionic gonadotropin [B-hCG]) or urine pregnancy test at inclusion.
11. Signed informed consent, which could be signed by a person on confidence in case the
neurologic status of the patient does not allow him to understand and/or to sign.
1. Histology other than DLBCL.
2. Positive HIV serology.
3. Active viral infection with Hepatitis B or C virus.
4. Preexisting immunodeficiency and/or organ transplant recipient.
5. Isolated Central Nervous System (CNS) relapse of systemic Non-Hodgkin's Lymphoma.
6. Prior treatment for PCNSL (except corticosteroids).
7. Isolated primary vitreo-retinal lymphoma.
8. Major surgery, within 4 weeks prior to the first dose of study drug. Stereotactic
biopsy and vitrectomy are not considered major surgery.
9. History of stroke or intracranial hemorrhage (except minor post biopsy hemorrhage)
within 6 months prior to inclusion.
10. Requires anticoagulation with warfarin or equivalent vitamin K antagonists.
11. Requires treatment with strong CYP3A4 inhibitors.
12. Pregnancy or lactation.
13. Clinically significant cardiovascular disease.
14. Any other active malignancy, except basocellular carcinoma and non-invasive cervix
cancer.
15. Inclusion in another experimental anti-cancer drug therapy.
16. No social security affiliation.
17. Persons under legal protection.