A Study of the Efficacy and Safety of Lenalidomide Combined to Escalating Doses of Chemotherapy in Intermediate-2-or High Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) With Del 5q

NCT00885508 | Unknown Phase 2 DMC

• 1 other identifier: GFM-Chimio-Rev-08
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 25

Brief Summary

In this trial, the investigators will test the combination of escalating doses of chemotherapy (starting at relatively low dose) with lenalidomide in intermediate-2-or high risk MDS and AML with del 5 q31. It is hoped that this combined therapy will further increase response rate in intermediate-2-or high risk MDS and AML with del 5 q31, without major toxicity in comparison to historical results obtained with chemotherapy alone in the same subset of patients.

Conditions

Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Acute Myeloid Leukemia

Keywords

MDS; AML; deletion 5q; Documented diagnosis of MDS, or CMML; with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2; or high-risk disease, or AML with an associated del 5q[31]; (the deleted chromosomal region must include 5q[31]),; with or without additional cytogenetic abnormalities

Outcome Measures

Primary Outcomes (1)

• Response (CR, mCR and Cri, according to IWG criteria for AML and IWG 2006 criteria for MDS) to the combination of lenalidomide and chemotherapy in adult high and int 2 MDS (IPSS) or AML with deletion 5q[31]

  At the end of induction

Secondary Outcomes (3)

• Duration of response

  At 1 and 2 years

• Progression to AML

  At 1 and 2 years

• Survival and safety of the combination of lenalidomide and chemotherapy

  At 1 and 2 years

Study Arms (1)

Aracytidine, Daunaurubicine, Lenalidomide

EXPERIMENTAL

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

1. Induction treatment Lenalidomide 10 mg once daily PO during 3 weeks . in combination with classical 7+3 chemotherapy. 2. Consolidation treatment 6 monthly courses of : Lenalidomide 10 mg/ d during the first 2 weeks in combination with classical 5+1 consolidation chemotherapy 3. Maintenance treatment Lenalidomide 10 mg/d 2 weeks every month until relapse In absence of toxicity, 20 additionnal patients will be included with lenalidomide dose of 25mg/J, then 20 other additionnals patients with Lenalidomide 50mg/J

Aracytidine, Daunaurubicine, Lenalidomide

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Must understand and voluntarily sign an informed consent form
• Must be able to adhere to the study visit schedule and other protocol requirements
• No contra indication to anthracycline based chemotherapy
• Documented diagnosis of MDS, or CMML with WBC \< 13,000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease, or AML 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 that the study medication could have a potential teratogenic risk
• Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception:
• Implant, Levonorgestrel-releasing intrauterine system (IUS) (prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection) , Medroxyprogesterone acetate depot, Tubal sterilization, Ovulation inhibitory progesterone-only pills (i.e., desogestrel), Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses.
• Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception.
• Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days from the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
• 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 tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence
• Male subjects must:
• Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
• Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.

You may not qualify if:

• Pregnant or lactating females.
• Contra indication to anthracycline based chemotherapy.
• Proliferative (WBC ≥ 13,000/mL) CMML.
• Prior ≥ grade-2 NCI CTCAE (v 3.0) allergic reaction to thalidomide.
• Prior desquamating (blistering) rash while taking thalidomide.
• Prior history of malignancy other than MDS unless the subject has been free of disease for ≥ 5 years.
• Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days .
• Less than 6 months since prior allogeneic bone marrow transplantation.
• Less than 3 months since prior autologous bone marrow or stem cell transplantation.
• Recombinant human erythropoietin (rHuEPO) therapy received within 28 days.
• Known HIV-1 positivity.
• Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study.
• Creatinine Clearance\< 50 ml/min
• Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) \> 3.0 x upper limit of normal (ULN)
• Serum total bilirubin \> 1.5 mg/dL (expect for unconjugated hyperbilirubinemia due to Gilbert's disease or secondary to MDS).

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Celgene Corporation: collaborator

Study Sites (25)

CH Angers

Angers, 49 000, France

Location

hopital Victor Dupouy

Argenteuil, 95107, France

Location

Centre Hospitalier de La Cote Basque

Bayonne, 64100, France

Location

Hôpital Avicenne

Bobigny, 93 000, France

Location

CHU Haut-Lévèque

Bordeaux, 33604, France

Location

Centre hospitalier de Chambéry

Chambéry, 73011, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, 63058, France

Location

Centre henri Mondor

Créteil, 94010, France

Location

Centre Hospitalier du Mans

Le Mans, 72037, France

Location

Centre Hospitalier de Lens

Lens, 32307, France

Location

centre hospitalier de Lens

Lens, 62307, France

Location

Hôpital Limoges

Limoges, 87046, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

CHU Brabois

Nancy, 54511, France

Location

CHU de nantes

Nantes, 44093, France

Location

Hôpital Archet1

Nice, 06202, France

Location

Hoiptal St Louis

Paris, 75475, France

Location

Hopital Cochin-Hematology

Paris, 75679, France

Location

Centre Hospitalier Joffre

Perpignan, 66046, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Hôpital Hautepierre

Strasbourg, 67098, France

Location

Hopital Purpan Service d'Hématologie Clinique

Toulouse, 31059, France

Location

CH de Valence

Valence, 26953, France

Location

Institut gustave Roussy

Villejuif, 94805, France

Location

Related Publications (1)

• Ades L, Prebet T, Stamatoullas A, Recher C, Guieze R, Raffoux E, Bouabdallah K, Hunault M, Wattel E, Stalnikiewicz L, Toma A, Dombret H, Vey N, Sebert M, Gardin C, Chaffaut C, Chevret S, Fenaux P. Lenalidomide combined with intensive chemotherapy in acute myeloid leukemia and higher-risk myelodysplastic syndrome with 5q deletion. Results of a phase II study by the Groupe Francophone Des Myelodysplasies. Haematologica. 2017 Apr;102(4):728-735. doi: 10.3324/haematol.2016.151894. Epub 2016 Dec 29.

  PMID: 28034993 DERIVED

Related Links

• Website of the french group of MDS

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Lionel Adès, MD

  Groupe Francophone des Myelodysplasies

  PRINCIPAL INVESTIGATOR

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: April 21, 2009
• First Posted: April 22, 2009
• Study Start: February 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 24, 2015

Record last verified: 2015-04

Locations

FR (25)