Erlotinib in Higher Risk Myelodysplastic Syndrome

NCT01085838 | Completed Phase 1 DMC

• 1 other identifier: GFM-ERLOTINIB-08
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 14

Brief Summary

The aim of this study is to evaluate the toxicity and therapeutic efficacy of erlotinib in high-risk myelodysplastic syndrome (MDS) patients (with at least 10% of bone marrow blasts) ineligible for or having failed intensive chemotherapy and ineligible or after failure of treatment with a hypomethylating agent.

Conditions

Myelodysplastic Syndrome

Keywords

Erlotinib; myelodysplastic syndrome

Outcome Measures

Primary Outcomes (1)

• The primary objective is to estimate the overall response rate (CR, PR, mCR The primary objective is to estimate the overall response rate (CR, PR, mCR and HI according to the IWG 2000 and 2006 criteria) in patients treated with erlotinib.

  After 12 weeks treatment

Secondary Outcomes (4)

• ·assessment of response duration

  While patient is on study/during follow-up.

• · survival

  While patient is on study/during follow-up.

• · treatment-related toxicity;

  While patient is on study/during follow-up.

• · correlation of prognostic parameters, response and survival, with the assessed biological parameters;

  While patient is on study/during follow-up.

Study Arms (3)

Cohort 1

EXPERIMENTAL

The first cohort of 5 patients will start with a dosage of 100 mg erlotinib daily

Drug: Erlotinib

Cohort 2

EXPERIMENTAL

The second cohort of patients will receive 150 mg of erlotinib daily

Drug: Erlotinib

Cohort 3

EXPERIMENTAL

The third cohort of five patients will be enrolled to receive 300 mg of erlotinib daily

Drug: Erlotinib

Interventions

Erlotinib DRUG

Erlotinib oral capsule, 100, 150, or 300 mg/day during 12 weeks at study start

Also known as: OSI-774

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

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

You may qualify if:

• Diagnosis of MDS according to the WHO classification, but also including RAEB in transformation as defined by the FAB classification (that is patients with up to 30% of blasts in the bone marrow), with the exception of patients with preceding myeloproliferative syndrome or LMMC;
• Higher-risk MDS as defined by a IPSS score \>1 (IPSS: Int-2 or High);
• Life expectancy \> 3 months;
• Percentage of bone marrow blasts \>10 and below 30%;
• Ineligible for or having failed intensive chemotherapy and ineligible for or having failed previous therapy with a hypomethylating agent;
• Age ≥ 18 years;
• Written informed consent;
• Patient must understand and voluntarily sign consent form;
• Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements;
• ECOG performance status between 0-2 at the time of screening;
• Females of childbearing potential (defined as a sexually mature woman who has not undergone a hysterectomy or who is not naturally postmenopausal for at least 24 consecutive months, that is who has had menses at any time during the preceding 24 consecutive months) have to have a negative pregnancy test;
• Adequate contraceptive methods should be carried out by all patients during therapy and for at least 2 weeks after completing therapy.
• No existing contra-indication to treatment with erlotinib.
• Health insurance.

You may not qualify if:

• Serum creatinine ≥ 1.5 x the upper limit of normal, or creatinine clearance ≤60 mL/min.
• Concomitant treatment with NSAIDS, warfarin, omeprazole, ranitidine or inducers (i.e. rifampicin, phenytoin; carbamazepin) or inhibitors (i.e. ketoconazole, ciprofloxacin, clarithromycin, voriconazole) of CYP3A4;
• Inadequate liver function as defined by a serum bilirubin ≥ 1.5 x the upper limit of normal (except in the case of confirmed moderate unconjugated hyperbilirubinemia due to intramedullary hemolysis, as observed frequently in MDS), and/or ASAT/ALAT/GGT levels ≥2 x the upper limit of normal;
• Known HIV-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;
• Vitamine B12 or folate deficiency;
• Pregnant or lactating females;
• Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within the 28 days preceding study entry;
• Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast), unless the subject has been disease-free for ≥3 years;
• Patients with a history of corneal disorders or another active ophthalmic disorder, active infections or other concomitant serious and uncontrolled medical conditions.
• History of interstitial lung disease or any active pulmonary disease.
• Patients with a history of myeloproliferative syndrome or LMMC

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Roche Pharma AG: collaborator

Study Sites (14)

CHU d'Angers

Angers, 49033, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

Centre Hospitalier du Mans

Le Mans, 72037, France

Location

CHRU Huriez

Lille, 59037, France

Location

CHRU de Limoges

Limoges, 87046, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69495, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

CHU Nantes

Nantes, 44093, France

Location

CHU Caremeau

Nîmes, 30029, France

Location

Hopital St Louis

Paris, 75475, France

Location

Hopital Cochin

Paris, 75679, France

Location

Hopital Purpan-Medecine interne

Toulouse, 31059, France

Location

Hopital Purpan

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sylvain Thepot, MD

  GFM/Hôpital Angers

  PRINCIPAL INVESTIGATOR

• Lionel Ades, MD

  GFM/Hôpital Saint Louis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: March 12, 2010
• Study Start: July 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: November 8, 2016

Record last verified: 2013-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (14)