## Protocol Section
### Identification Module
**NCT ID:** NCT01718379

**Brief Title:** Lenalidomide in Subject With Low and Intermediate-1 Risk MDS and Without Chromosome 5 Abnormality.

**Official Title:** A Phase II Study Evaluating the Efficacy/Safety of Lenalidomide With or Without Epoetin Beta in Transfusion-dependent ESA-resistant Patients With IPSS Low- and Intermediate-1 Risk Myelodysplastic Syndromes Without Chromosome 5 Abnormality.

#### Organization Study ID Info
**ID:** GFM-Len-Epo-08
#### Organization
**Class:** OTHER
**Full Name:** Groupe Francophone des Myelodysplasies
### Status Module
#### Completion Date
**Date:** 2016-06

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2016-11-08

**Type:** ESTIMATED

**Last Update Submit Date:** 2016-11-07

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2012-11

**Type:** ACTUAL

#### Start Date
**Date:** 2010-07

**Status Verified Date:** 2016-11

#### Study First Post Date
**Date:** 2012-10-31
**Type:** ESTIMATED
**Study First Submit Date:** 2012-10-23
**Study First Submit QC Date:** 2012-10-29
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Celgene

**Class:** INDUSTRY

**Name:** Roche Pharma AG

#### Lead Sponsor

**Class:** OTHER

**Name:** Groupe Francophone des Myelodysplasies

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of the present study is to assess, through a randomized phase II trial, the efficacy and safety of Lenalidomide with or without Epoetin beta in transfusion-dependent, ESA-resistant, IPSS low and intermediate-1 risk MDS patients without chromosome 5 abnormality.

Patients will receive either Lenalidomide alone or Lenalidomide and Epoetin beta for 4 months. Responders will be eligible for maintenance treatment with cycles identical to the first cycles, until relapse occurs or until unacceptable toxicity.

**Detailed Description:** This is a multi-center, open-label, randomized, Phase II study.

Patients will be treated either with arm A or B

* Arm A: Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses.
* Arm B: Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses combined with weekly subcutaneous injections of Epoetin beta (60,000 Units/w).

Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria.

Maintenance: responders will continue to follow the corresponding treatment arm until relapse occurs; non responders at Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria.

in arm A will be considered in failure of treatment and the introduction of Epoetin beta is at the discretion of the physician.

The patients will be followed every 3 months for 12 months

### Conditions Module

**Conditions:**

- Myelodysplastic Syndromes

**Keywords:**

- Myelodysplasia

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 132

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses.

Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria.

Maintenance: responders will continue to follow the corresponding treatment arm until relapse occurs; non responders at cycle 4 in arm A will be considered in failure of treatment and the introduction of Epoetin beta is at the discretion of the physician.

The patients will be followed every 3 months for 12 months

**Intervention Names:**

- Drug: Lenalidomide

**Label:** Arm A

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses combined with weekly subcutaneous injections of Epoetin beta (60,000 Units/w).

Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria.

Maintenance: responders will continue to follow the corresponding treatment arm until relapse occurs; non responders at cycle 4 in arm A will be considered in failure of treatment and the introduction of Epoetin beta is at the discretion of the physician.

The patients will be followed every 3 months for 12 months

**Intervention Names:**

- Drug: Epoetin beta

**Label:** Arm B

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Arm A

**Description:** Lenalidomide:10 mg per day during 21 days

**Name:** Lenalidomide

**Other Names:**

- Revlimid

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Arm B

**Description:** Epoetin beta: 60,000 Units/week.

**Name:** Epoetin beta

**Other Names:**

- NEORECORMON

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Primary outcome is a complete or partial response defined by the IWG 2006 criteria observed after 4 months of treatment. Comparison in the rate of response between the two groups will be performed with Chi-square test or if necessary Fisher exact test.

Same analyzes will be performed with the IWG 2000 response definition .

**Measure:** Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant

**Time Frame:** After 4 months of treatment

#### Secondary Outcomes

**Description:** * Safety of Lenalidomide and of its combination with Epoetin beta: adverse events (type, frequency, severity) and relationship of adverse events to study drug
* % of major HI-E and minor HI-E after 4 courses according to IWG 2000 criteria
* Erythroid response duration
* Time to response
* Time to progression according to IPSS
* RBC transfusion independence
* Prognostic factors of response
* Survival
* Quality of life

**Measure:** will be to assess the safety of Lenalidomide and of its combination with Epoetin beta

**Time Frame:** After 2 months of treatment

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

MDS defined as

* Low or int-1 IPSS score
* Documented absence of chromosome 5 abnormality (del(5q) or -5 karyotype)
* De novo MDS, excluding therapy-related MDS AND
* Transfusion dependance (requirement of at least 4 units of RBC transfusions every 8 weeks )
* Resistance or loss of response to a previous treatment with Epoetin alpha/beta (at least 60,000 Units/w) or Darbepoetin (at least 250 µg/w), for at least 12 weeks
* Ineligibility for allogeneic stem cell transplantation or intensive chemotherapy during the next 12 months
* ECOG performance status ≤ 2
* Age ≥ 18 years
* Life expectancy ≥ 3 months
* Adequate liver function (transaminases serum levels ≤ 3N)
* Adequate renal function (calculate creatinine clearance \> 50 ml/min)
* Female subjects of chilbearing potential\* must :

Agree to use effective contraception without interruption throughout the study and for at least 4 weeks after the end of treatment

• Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and during one week after end of treatment if their partner is of childbearing potential.

Exclusion Criteria:

* Active serious infection not controlled by oral or intravenous antibiotics
* Platelets less than 50 G/L
* Prior history of deep vein thrombosis or pulmonary embolism
* Previous treatment by Thalidomide
* Treatment with any investigational antileukemic agent or chemotherapy at least 6 weeks prior to study entry and lack of full recovery from side effects due to prior therapy independent of when that therapy were given
* Rapidely progressive disease with copromised organ function judged to be life-threatening by the Investigator
* Pregnant or lactating female
* Known human immunodeficiency virus (HIV) infection
* Known active hepatitis B and/or C virus infection
* Hypersensitivity or intolerance to Lenalidomide or any of the excipients
* Hypersensitivity to Epoetin beta or any of the excipients
* Uncontrolled arterial hypertension
* Any history of malignancy (other than myelodysplastic syndrome) unless the patient has remained disease free for more than 5 years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** CHU Albert Michallon

**Country:** France

**Facility:** Hematology Dpt, Service d'Hématologie Clinique

**State:** Grenoble

**Zip:** 38043

**Location 2:**

**City:** Le Kremlin-Bicêtre

**Country:** France

**Facility:** Hematology Dpt, CHU de Bicêtre

**State:** Ile de France

**Zip:** 94275

**Location 3:**

**City:** Paris

**Country:** France

**Facility:** Hematology Dpt, CHU Cochin

**State:** Ile de France

**Zip:** 75679

**Location 4:**

**City:** Amiens

**Country:** France

**Facility:** Chu Amiens

**Zip:** 80054

**Location 5:**

**City:** Angers

**Country:** France

**Facility:** CHU Angers

**Zip:** 43033

**Location 6:**

**City:** Avignon

**Country:** France

**Facility:** Hematology Dpt, CH d'Avignon-305 rue Follereau-

**Zip:** 84000

**Location 7:**

**City:** Bayonne

**Country:** France

**Facility:** CH de la Cote Basque

**Zip:** 64 100

**Location 8:**

**City:** Blois

**Country:** France

**Facility:** centre de Blois

**Zip:** 41016

**Location 9:**

**City:** Bobigny

**Country:** France

**Facility:** Hopital Avicenne

**Zip:** 93009

**Location 10:**

**City:** Bordeaux

**Country:** France

**Facility:** Hematology Dpt, CHU Haut-Lévèque

**Zip:** 33604

**Location 11:**

**City:** Boulogne Sur Mer

**Country:** France

**Facility:** Hôpital Boulogne Sur Mer

**Zip:** 62321

**Location 12:**

**City:** Brest

**Country:** France

**Facility:** hôpital Morvan

**Zip:** 29609

**Location 13:**

**City:** Caen

**Country:** France

**Facility:** CHU Clémenceau

**Zip:** 14033

**Location 14:**

**City:** Carcassonne

**Country:** France

**Facility:** CH de Carcassonne

**Zip:** 11890

**Location 15:**

**City:** Cergy-pontoise

**Country:** France

**Facility:** Hematology Dpt, CH René Dubos

**Zip:** 95303

**Location 16:**

**City:** Clermont-Ferrand

**Country:** France

**Facility:** CHU de Clermont-Ferrand

**Zip:** 63058

**Location 17:**

**City:** Compiègne

**Country:** France

**Facility:** CH de Compiègne

**Zip:** 60321

**Location 18:**

**City:** Corbeil-essonnes

**Country:** France

**Facility:** Hematology Dpt, Hôpital Sud Francilien

**Zip:** 91100

**Location 19:**

**City:** Créteil

**Country:** France

**Facility:** hopital Henri Mondor

**Zip:** 94010

**Location 20:**

**City:** Dijon

**Country:** France

**Facility:** CHU de Dijon

**Zip:** 21034

**Location 21:**

**City:** Le Chesnay

**Country:** France

**Facility:** Hematology Dpt, Hôpital Versailles

**Zip:** 78157

**Location 22:**

**City:** Le mans

**Country:** France

**Facility:** Hematology Dpt,CH Le mans

**Zip:** 72037

**Location 23:**

**City:** Lille

**Country:** France

**Facility:** CHRU Huriez

**Zip:** 59037

**Location 24:**

**City:** Lille

**Country:** France

**Facility:** Hopital Saint-Vincent de Paul

**Zip:** 59160

**Location 25:**

**City:** Limoges

**Country:** France

**Facility:** CHRU de Limoges

**Zip:** 87046

**Location 26:**

**City:** Lyon

**Country:** France

**Facility:** Hematology Dpt, Centre Hospitalier Lyon Sud

**Zip:** 69495

**Location 27:**

**City:** Mantes-la-jolie

**Country:** France

**Facility:** CH de Mantes-la-jolie

**Zip:** 78201

**Location 28:**

**City:** Marseille

**Country:** France

**Facility:** Institut Paoli Calmettes

**Zip:** 13009

**Location 29:**

**City:** Nancy

**Country:** France

**Facility:** Hematology Dpt, CHU Brabois

**Zip:** 54511

**Location 30:**

**City:** Nantes

**Country:** France

**Facility:** Hematology Dpt, CHU de nantes

**Zip:** 44093

**Location 31:**

**City:** Nice

**Country:** France

**Facility:** Hematology Dpt, CHU Archet

**Zip:** 06202

**Location 32:**

**City:** Nimes

**Country:** France

**Facility:** Hematology Dpt, CHU Caremeau

**Zip:** 30029

**Location 33:**

**City:** Orléans

**Country:** France

**Facility:** Hematology Dpt, CHR La Source orléans

**Zip:** 45067

**Location 34:**

**City:** Paris Saint Cloud

**Country:** France

**Facility:** centre René Huguenin

**Zip:** 92210

**Location 35:**

**City:** Paris

**Country:** France

**Facility:** Hematology Dpt, Hôpital la pitié-Salpétrière

**Zip:** 75013

**Location 36:**

**City:** Paris

**Country:** France

**Facility:** Hematology Dpt, Hopital Saint Louis

**Zip:** 75475

**Location 37:**

**City:** Paris

**Country:** France

**Facility:** Hopital Saint Antoine

**Zip:** 75571

**Location 38:**

**City:** Perpignan

**Country:** France

**Facility:** Hematology Dpt, Hôpital Maréchal Joffre

**Zip:** 66046

**Location 39:**

**City:** Poitiers

**Country:** France

**Facility:** Hôpital Jean Bernard

**Zip:** 86021

**Location 40:**

**City:** Pringy cedex

**Country:** France

**Facility:** Hematology Dpt, Centre Hospitalier de la région d'Annecy

**Zip:** 74374

**Location 41:**

**City:** Reims

**Country:** France

**Facility:** CHRU de Reims

**Zip:** 51092

**Location 42:**

**City:** Rennes

**Country:** France

**Facility:** CHU Pontchaillou

**Zip:** 35033

**Location 43:**

**City:** Rouen

**Country:** France

**Facility:** Centre Henri Becquerel

**Zip:** 76038

**Location 44:**

**City:** Sint Quentin

**Country:** France

**Facility:** CH de Saint Quentin

**Zip:** 02321

**Location 45:**

**City:** Strasbourg

**Country:** France

**Facility:** Chu Strasbourg

**Zip:** 67098

**Location 46:**

**City:** Toulouse

**Country:** France

**Facility:** Hematology Dpt, CHU PURPAN

**Zip:** 31059

**Location 47:**

**City:** Tours

**Country:** France

**Facility:** Hematology Dpt, CH CHU Bretoneau

**Zip:** 37044

**Location 48:**

**City:** Monaco

**Country:** Monaco

**Facility:** centre hopitalier princesse Grace

**Zip:** 98012

#### Overall Officials

**Official 1:**

**Affiliation:** Groupe Francophone des Myelodysplasies

**Name:** Andréa TOMA, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Groupe Francophone des Myelodysplasies

**Name:** François Dreyfus, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Chesnais V, Renneville A, Toma A, Lambert J, Passet M, Dumont F, Chevret S, Lejeune J, Raimbault A, Stamatoullas A, Rose C, Beyne-Rauzy O, Delaunay J, Solary E, Fenaux P, Dreyfus F, Preudhomme C, Kosmider O, Fontenay M; Groupe Francophone des Myelodysplasies. Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion. Blood. 2016 Feb 11;127(6):749-60. doi: 10.1182/blood-2015-04-640128. Epub 2015 Dec 1.

**PMID:** 26626993

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000001855

- Term: Bone Marrow Diseases

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000011230

- Term: Precancerous Conditions

- ID: D000009369

- Term: Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M14164

- Name: Preleukemia

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

- ID: M12145

- Name: Myelodysplastic Syndromes

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

- ID: M5134

- Name: Bone Marrow Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14111

- Name: Precancerous Conditions

- Relevance: LOW

- As Found: Unknown

- ID: T3993

- Name: Myelodysplastic Syndromes

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

### Condition Browse Module - Meshes

- ID: D000011289

- Term: Preleukemia

- ID: D000009190

- Term: Myelodysplastic Syndromes

- ID: D000013577

- Term: Syndrome

### Intervention Browse Module - Ancestors

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000020533

- Term: Angiogenesis Inhibitors

- ID: D000043924

- Term: Angiogenesis Modulating Agents

- ID: D000006133

- Term: Growth Substances

- ID: D000006131

- Term: Growth Inhibitors

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

### Intervention Browse Module - Browse Leaves

- ID: M1725

- Name: Lenalidomide

- Relevance: HIGH

- As Found: Respiratory

- ID: M314

- Name: Epoetin Alfa

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M22318

- Name: Angiogenesis Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9231

- Name: Growth Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077269

- Term: Lenalidomide

### Misc Info Module

- Version Holder: 2024-05-24
