Lenalidomide Combined to Azacitidine in Intermediate-2 or High Risk MDS With Del 5q
GFM-AZA-REV-09
A Phase II Study of the Efficacy and Safety of Lenalidomide Combined to Azacitidine in Intermediate-2 or High Risk MDS With Del 5q
1 other identifier
interventional
50
1 country
34
Brief Summary
Higher risk MDS with del(5q) carry very poor prognosis, but show some response to azacitidine and Lenalidomide as single agents . The combination of Lenalidomide and Azacytidine is currently tested in non del 5q MDS patients. Preliminary results have been recently presented at ASH meeting (Sekeres et al, 2007). Overall, the combination of Lenalidomide and Azacitidine is well-tolerated and early results suggest some efficacy in advanced MDS without del 5q. In this trial, we will combine Lenalidomide to Azacytidine in higher risk MDS with del (5q). Patients will receive azacitidine( 75mg/m2/day for 5 days every 28 days) combined to escalating doses of lenalidomide (starting at relatively low dose). For patients in hematological CR, PR, HI or marrow CR after cycle 2 or 4, it is mandatory to continue on Azacitidine + Lenalidomide as long as there is no unacceptable toxicity or overt progression, with the schedule that yielded response. In patient still responding after 52 weeks, the drug will continue to be supplied, and follow up until death will be continued in all patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2010
Longer than P75 for phase_2
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 16, 2010
CompletedFirst Posted
Study publicly available on registry
March 17, 2010
CompletedStudy Start
First participant enrolled
March 25, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 25, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
July 25, 2016
CompletedDecember 15, 2017
December 1, 2017
6.3 years
March 16, 2010
December 14, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
To identify the "safe most successful dose"(sMSD) that is the dose level where the probabilities of success is maximized across the dose levels and the toxicity rate is kept within acceptable boundaries.
Briefly, dose limiting toxicity would be defined by having greater than 30% occurrence of unexpected grade III-IV hematological or non hematological toxicity. Efficacy would be defined as a response rate of 40% after 2 cycles. Overall, 49 patients will be included.
2 and 4 months of treatment
Secondary Outcomes (1)
response rate and safety
36 months
Study Arms (1)
Azacitidine, Lenalidomide
EXPERIMENTALInterventions
Azacitidine: 75mg/m2/d for 5 days per cycle of 28 days. Lenalidomide: 5mg/day during 14 days for cohort 1. Lenalidomide: 5mg/day during 21 days for cohort 2. Lenalidomide: 10mg/day during 21 days for cohort 3.
Eligibility Criteria
You may qualify if:
- age \> ou = 18 years and \< 75 years.
- must understand and voluntarily sign an informed consent form.
- patient considered ineligible for intensive chemotherapy due to age, cardiac contraindication to anthracyclines, comorbidities, previous failure of intensive chemotherapy, or patient willing to avoid intensive chemotherapy.
- must be able to adhere to the study visit schedule and other protocol requirements.
- prior thalidomide allowed.
- documented diagnosis of MDS (according to FAB definition, ie. with marrow blasts up to 30%, or CMML with WBC \< 13000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease.
- with an associated del 5q\[31\](the deleted chromosomal region must include 5q\[31\]), with or without additional cytogenetic abnormalities.
- female subjects of childbearing potential must:
- understand the study drug is expected to have a teratogenic risk.
- agree to have a medically supervised pregnancy test with a minimum sensitivity of 25mIU/ml on the day of the study visit or in the 3 days prior to the study visit once the subject has been on effective contraception for at least weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence. the test should ensure the subject is not pregnant when she starts treatment.
- agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. these pregnancy tests should be performed on the day of the study visit or in the 3 days prior to the study visit.
- this requirement also applies to women of childbearing potential who practice complete and continued abstinence.
- \* agree to use, and to be able to comply with effective contraception without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy(including doses interruptions)and for 3 months after the end of the study drug therapy even if she has amenorrhea this applies unless the subject commits to absolute and continuous abstinence confirmed on a monthly basis, to avoid pregnancy for the duration of study.
- the following are effective methods of contraception:
- implant
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Groupe Francophone des Myelodysplasieslead
- Celgenecollaborator
Study Sites (34)
Hôpital kremlin Bicêtre
Le Kremlin-Bicêtre, IDF, 94275, France
Chu Brabois
Nancy, Vandoeuvre, 54511, France
CHU d'Amiens
Amiens, 80054, France
CHU Angers
Angers, 43033, France
Hôpital de la cote basque
Bayonne, 64100, France
Hôpital Avicenne
Bobigny, 93009, France
CHU Haut-Lévèque
Bordeaux, 33604, France
CH René Dubos
Cergy-Pontoise, 95303, France
CHU de
Clermont-Ferrand, 63058, France
Centre Hospitalier Sud-Francilien
Corbeil-Essonnes, 91106, France
CHU Henri Mondor
Créteil, 94010, France
CHU de Grenoble
Grenoble, 38043, France
CH Le mans
Le Mans, 72037, France
Centre Hospitalier de Lens
Lens, 32307, France
CHRU de Limoges
Limoges, 87046, France
Hôpital Edouard Heriot, dpt Hématologie Clinique
Lyon, 69437, France
Institut Paoli-Calmette, Département d'hématologie
Marseille, 13009, France
Centre Hospitalier de Meaux
Meaux, 77100, France
Hopital de l'Hotel Dieu, Hematology Dpt
Nantes, 44093, France
CHU Archet
Nice, 06202, France
CHR La Source orléans
Orléans, 45067, France
Hôpital Saint Louis
Paris, 75010, France
Saint-Louis Hospital
Paris, 75010, France
Hôpital Saint-Antoine
Paris, 75012, France
Hôpital la pitié-Salpétrière
Paris, 75013, France
Hopital Cochin Service d'Hématologie
Paris, 75679, France
Hôpital Maréchal Joffre
Perpignan, 66046, France
Hôpital Jean-Bernard
Poitiers, 86021, France
centre hospitalier Jacques Puel
Rodez, 12027, France
Hôpital Henri Becquerel
Rouen, 76038, France
Hôpital Purpan, médecine Interne
Toulouse, 31059, France
Hôpital PURPAN, Service d'Hématologie Clinique
Toulouse, 31059, France
CHU Bretonneau
Tours, 37044, France
Institut gustave Roussy
Villejuif, 94805, France
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lionel ADES, MD
GFM
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2010
First Posted
March 17, 2010
Study Start
March 25, 2010
Primary Completion
July 25, 2016
Study Completion
July 25, 2016
Last Updated
December 15, 2017
Record last verified: 2017-12