Gemtuzumab Ozogamicin+Cytarabine vs Idarubicin+Cytarabine in Elderly Patients With AML.Mylofrance 4

NCT02473146 | Completed Phase 2 DMC

• 1 other identifier: 2014-001395-65
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 21

Brief Summary

Purpose : The main objective of this study is to assess the efficacy and tolerance of the addition of repeated doses of low doses (3mg/m2) of Gemtuzumab Ozogamicin (GO) in addition with standard doses of Ara-C in previously untreated patients aged 60 to 80 years with de novo acute myeloblastic leukemia (AML) and non adverse cytogenetics. The main end point for efficacy is 2 years-event free survival. The secondary efficacy endpoints are CR/Cri rates, cumulative incidence of relapse and overall survival. The secondary endpoints for safety are early death rate (before day 30 and 60), grade 3 to 5 adverse events and severe adverse events, cardiac toxicity and quality of life. Additional secondary endpoints are treatment by covariate interactions with respect to biological characteristics present at diagnosis (CD33 positivity, cytogenetic, molecular abnormalities) or after treatment (Minimal residual disease levels). This study is an exploratory study. Patients will be allocated at inclusion with a 2/1 ratio either to receive treatment with GO and cytarabine or Idarubicin and cytarabine in a 3+7 regimen similar to the "backbone" ALFA 1200 scheme used concurrently by the ALFA group as treatment of AML patients aged \>60 years. Primary objective. The primary objective is to assess the efficacy of two doses of Gemtuzumab ozogamicin (GO) during induction and one dose of GO during first consolidation in combination with Cytarabine in elderly patients with AML in the non adverse cytogenetics-risk group.

Conditions

Acute Myeloid Leukemia

Keywords

AML; untreated; 60-80 years old; favorable and intermediate karyotype

Outcome Measures

Primary Outcomes (1)

• EFS (defined as the time from randomization to the date of assessment of response if CR or Cri had not been achieved, relapse or death)

  Endoint for the primary objective of efficacy is EFS defined as the time from randomization to the date of assessment of response if CR or Cri had not been achieved, relapse or death.

  5 years

Secondary Outcomes (2)

• Composite measure for Efficacy assessed by CR/Cri rates, cumulative incidence of relapse, overall survival.

  5 years

• Composite measure for safety

  5 years

Study Arms (2)

Mylotarg Arm

EXPERIMENTAL

After randomization patients in the experimental arm are assigned to receive chemotherapy with: Gemtuzumab Ozogamicin 3 mg/m2 (maximum dose: 5 mg) per IV, 60mn on Day 1 and 4 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7

Drug: Gemtuzumab ozogamicin (GO)

Control Arm

NO INTERVENTION

After randomization patients in the control arm are assigned to receive chemotherapy with Idarubicin 12mg/m2 per IV, 30mn on Day 1,2,3 Cytarabine 200 mg/m2 per CIV over 24h on Day 1 to 7

Interventions

Gemtuzumab ozogamicin (GO) DRUG

Also known as: Mylotarg

Mylotarg Arm

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a morphologically proven diagnosis AML and both the following criteria:
• Age ≥ 60 years and \< 80 years.
• Not previously treated for their disease.
• With favourable or intermediate-risk cytogenetics. (Patients with urgent clinical need to begin treatment might be included before cytogenetic results, when necessary if they do not respond to Hydroxyurea. Patients might be included if the cytogenetic results are not expected in a time limit \< 5 days after AML diagnosis).
• Fit to receive intensive chemotherapy
• Cardiac function determined by radionucleide or echography within normal limits.
• Signed informed consent

You may not qualify if:

• M3-AML
• Presence of adverse cytogenetics (according to European LeukemiaNet recommendation.) (17) defined as one of the following abnormalities: -5/5q-, -7, t(6;9), t(v;11q23) excluding t(9;11), inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), complex karyotype (3+ abnormalities)
• Secondary AML following treatment with radiotherapy or chemotherapy.
• AML following previously known myeloproliferative or myelodysplastic syndrome.
• ECOG performance status (PS) 0 to 3
• Serum creatinin level \> or = 2.5N; AST and ALT level \> or = 2.5N; total bilirubin level \> or = 2N

Sponsors & Collaborators

• Versailles Hospital: lead

Study Sites (21)

C.H.U d'Amiens - Hôpital Sud

Amiens, France

Location

Hôpital V. Dupouy

Argenteuil, France

Location

CH Avicenne

Bobigny, France

Location

CHU Caen

Caen, France

Location

HIA Percy

Clamart, 92140, France

Location

Hopital Henri Mondor

Créteil, France

Location

CHU Dijon

Dijon, France

Location

CH Dunkerque

Dunkirk, France

Location

CH Versailles

Le Chesnay, 78157, France

Location

Hôpital Huriez, CHU de Lille

Lille, France

Location

CHU Limoges

Limoges, France

Location

Hôpital de la Conception

Marseille, 13005, France

Location

Centre Antoine Lacassagne

Nice, 06100, France

Location

CHU d'Orléans

Orléans, 45100, France

Location

Hopital Necker

Paris, France

Location

Hopital St Louis

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

CHU Lyon Sud

Pierre-Bénite, France

Location

Centre H Becquerel

Rouen, France

Location

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, 42270, France

Location

IGR

Villejuif, France

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Juliette LAMBERT, MD

  Versailles Hospital

  PRINCIPAL INVESTIGATOR

• Sylvie CASTAIGNE, MD

  Versailles Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical coordinator

Study Record Dates

• First Submitted: April 29, 2015
• First Posted: June 16, 2015
• Study Start: November 18, 2015
• Primary Completion: February 26, 2021
• Study Completion: September 7, 2023
• Last Updated: February 2, 2024

Record last verified: 2024-02

Locations

FR (21)