Lenalidomide Combined to Azacitidine in Intermediate-2 or High Risk MDS With Del 5q (GFM-AZA-REV-09)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Groupe Francophone des Myelodysplasies
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier:
NCT01088373
First received: March 16, 2010
Last updated: March 12, 2014
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: Azacitidine combined to Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Efficacy and Safety of Lenalidomide Combined to Azacitidine in Intermediate-2 or High Risk MDS With Del 5q

Resource links provided by NLM:


Further study details as provided by Groupe Francophone des Myelodysplasies:

Primary Outcome Measures:
  • 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. [ Time Frame: 2 and 4 months of treatment ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • response rate and safety [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    1. response rate (according to IWG 2006 criteria) to the combination of lenalidomide and azacitidine in adult high and int 2 MDS with del 5q
    2. safety (particularly hematological toxicity) of the combination of Lenalidomide and azacitidine in int-2 and high risk MDS with del 5q [31].
    3. duration of response,
    4. progression to AML,
    5. and overall survival.


Estimated Enrollment: 49
Study Start Date: March 2010
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azacitidine, Lenalidomide Drug: Azacitidine combined to Lenalidomide
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.
Other Names:
  • Vidaza.
  • Revlimid.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. age > ou = 18 years and < 75 years.
  2. must understand and voluntarily sign an informed consent form.
  3. 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.
  4. must be able to adhere to the study visit schedule and other protocol requirements.
  5. prior thalidomide allowed.
  6. 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.
  7. with an associated del 5q[31](the deleted chromosomal region must include 5q[31]), with or without additional cytogenetic abnormalities.
  8. 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
    • levonorgestrel-releasing intrauterine system(IUS)
    • Medroxyprogesterone acetate depot, tubal sterilization.
    • sexual intercourse with a vasectomised male partner only(vasectomised must be confirmed by two negative semen analyses), ovulation inhibitory progesterone-only pills(i.e.desogestrel).

    if not established on effective contraception, the female subject must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated.

    Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking lenalidomide and dexamethasone, combined oral contraceptive pills are not recommended. If a female subject is currently using combined oral contraception, the patient should switch to one of the effective methods listed above. The risk of venous thromboembolism continues for 4 to 6 weeks after discontinuing combined oral contraception. The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone.

    Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia .

    Copper-releasing intrauterine devices are generally not recommended due to the potential risks of infection at the time of insertion and menstrual blood loss which may compromise patients with neutropenia or thrombocytopenia.

    • Understand that even if she has amenorrhea, she must follow all the advice on effective contraception.
    • She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy
  9. Male patients must :

    • Agree the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential. during the entire period of treatment, even if disruption of treatment and during 3 months after end of treatment
    • Agree not to conceive during treatment and study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy
    • Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
    • Agree to learn about the procedures for preservation of sperm., before starting treatment
  10. All subjects must :

    • Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
    • Agree not to share study medication with another person and to return all unused study drug to the investigator.
  11. Signed informed consent prior to start of any study-specific procedures,
  12. Ability to participate to a clinical trial and adhere to study procedures.

    • Criteria for women of non-childbearing potential :

A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria:

  • Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year (amenorrhoea following cancer therapy does not rule out childbearing potential)
  • Premature ovarian failure confirmed by a specialist gynaecologist
  • Previous bilateral salpingo-oophorectomy, or hysterectomy
  • XY genotype, Turner syndrome, uterine agenesis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088373

Contacts
Contact: Lionel ADES, MD 033170207022 lionel.ades@sls.aphp.fr

Locations
France
Hôpital kremlin Bicêtre Active, not recruiting
Kremlin Bicêtre, IDF, France, 94275
Chu Brabois Active, not recruiting
Nancy, Vandoeuvre, France, 54511
CHU d'Amiens Active, not recruiting
Amiens, France, 80054
CHU Angers Active, not recruiting
Angers, France, 43033
Hôpital de la cote basque Active, not recruiting
Bayonne, France, 64100
Hôpital Avicenne Recruiting
Bobigny, France, 93009
Contact: Thorsten Braun, MD    (0) 33 1 48 95 70 51    thorsten.braun@avc.aphp.fr   
Principal Investigator: Thorsten Braun, MD         
CHU Haut-Lévèque Recruiting
Bordeaux, France, 33604
Contact: Krimo BOUABDALLAH, MD    +33 5-57-65-65-11    krimo.bouabdallah@chu-bordeaux.fr   
Contact: mathieu Sauvezie    05 57 62 31 09    mathieu.sauvezie@chu-bordeaux.fr   
Principal Investigator: Krimo Bouabdallah, MD         
CH René Dubos Active, not recruiting
Cergy-pontoise, France, 95303
CHU de Recruiting
Clermont Ferrand, France, 63058
Contact: Benoît de RENZIS, MD    +33 4 73 75 00 68    bderenzis@chu-clermontferrand.fr   
Contact: Gaelle Piquemal    +33 4 73 75 07 48    gpiquemal@chu-clermontferrand.fr   
Principal Investigator: Benoît de RENZIS, MD         
Centre Hospitalier Sud-Francilien Active, not recruiting
Corbeil-Essonnes, France, 91106
CHU Henri Mondor Active, not recruiting
Creteil, France, 94010
CHU de Grenoble Active, not recruiting
Grenoble, France, 38043
CH Le mans Active, not recruiting
Le mans, France, 72037
Centre Hospitalier de Lens Active, not recruiting
Lens, France, 32307
CHRU de Limoges Active, not recruiting
Limoges, France, 87046
Hôpital Edouard Heriot, dpt Hématologie Clinique Active, not recruiting
Lyon, France, 69437
Institut Paoli-Calmette, Département d'hématologie Recruiting
Marseille, France, 13009
Contact: Norbert VEY, PHD, MD    +33 4 91 22 37 54    veyn@marseille.fnclcc.fr   
Contact: Nathalie NICOLAS    +33 04-91-22-36-87    nicolasn@marseille.fnclcc.fr   
Principal Investigator: Norbert VEY, PHD,MD         
Centre Hospitalier de Meaux Not yet recruiting
Meaux, France, 77100
Contact: Loïc Fouillard, MD    033164653876    l-fouillard@ch-meaux.fr   
Principal Investigator: Loïc Fouillard, MD         
Hopital de l'Hotel Dieu, Hematology Dpt Recruiting
Nantes, France, 44093
Contact: Jacques DELAUNAY, MD    +33 2 40 08 32 71    jacques.delaunay@chu-nantes.fr   
Contact: Marie-Aude Rambaud       MarieAude.rambaud@chu-nantes.fr   
Principal Investigator: Jacques DELAUNAY, MD         
CHU Archet Active, not recruiting
Nice, France, 06202
CHR La Source orléans Active, not recruiting
Orléans, France, 45067
Saint-Louis Hospital Recruiting
Paris, France, 75010
Contact: Hervé Dombret, MD    +33 1 42 49 96 43    herve.dombret@sls.aphp.fr   
Contact: Marie-Thérèse Trémorin    +33 1 57 27 67 04    marie-therese.tremorin@sls.aphp.fr   
Principal Investigator: Hervé Dombret, MD         
Hôpital la pitié-Salpétrière Active, not recruiting
Paris, France, 75013
Hôpital Saint-Antoine Recruiting
Paris, France, 75012
Contact: Françoise Isnard, MD    033149282622    francoise.isnard@sat.aphp.fr   
Contact: souhila Ikhlef       souhila.ikhlef@sat.aphp.fr   
Principal Investigator: Françoise Isnard, MD         
Hôpital Saint Louis Recruiting
Paris, France, 75010
Contact: Pierre Fenaux, MD    033170207022    pierre.fenaux@sls.aphp.fr   
Principal Investigator: Pierre Fenaux, MD         
Hopital Cochin Service d'Hématologie Recruiting
Paris, France, 75679
Contact: François DREYFUS, Pr    +33 1 58 41 21 20    francois.dreyfus@cch.aphp.fr   
Contact: Rosa Sapena, PhD    +33 1 42 34 83 22    rosa.sapena@cch.aphp.fr   
Principal Investigator: Sophie Park, MD         
Sub-Investigator: François Dreyfus, Pr         
Hôpital Maréchal Joffre Active, not recruiting
Perpignan, France, 66046
Hôpital Jean-Bernard Active, not recruiting
Poitiers, France, 86021
centre hospitalier Jacques Puel Active, not recruiting
Rodez, France, 12027
Hôpital Henri Becquerel Recruiting
Rouen, France, 76038
Contact: Aspasia Stamatoullas, MD    +33 2 32 08 22 88    astamatoullas@rouen.fnclcc.fr   
Contact: Béatrice Perre    +33 2 32 08 24 96    Beatrice.Perre@rouen.fnclcc.fr   
Principal Investigator: Aspasia Stamatoullas, MD         
Hôpital Purpan, médecine Interne Active, not recruiting
Toulouse, France, 31059
Hôpital PURPAN, Service d'Hématologie Clinique Recruiting
Toulouse, France, 31059
Contact: Christian RECHER, PHD, MD    +33 5 61 77 96 77    recher.c@chu-toulouse.fr   
Contact: Isabelle de Ponnat    +33 5 61 77 90 41    deponnat.i@chu-toulouse.fr   
Principal Investigator: Christian RECHER, PHD,MD         
CHU Bretonneau Active, not recruiting
Tours, France, 37044
Institut gustave Roussy Active, not recruiting
Villejuif, France, 94805
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Celgene Corporation
Investigators
Principal Investigator: Lionel ADES, MD GFM
  More Information

Additional Information:
No publications provided

Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT01088373     History of Changes
Other Study ID Numbers: AZA-REV-09
Study First Received: March 16, 2010
Last Updated: March 12, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Precancerous Conditions
Azacitidine
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014