DNR and AraC Combined to Fractionated Mylotarg® in Patients With First Relapse of AML (MYLOFRANCE2)

A Dose-finding Phase I/II Trial of Daunorubicin and Cytarabine Combined to Fractionated Mylotarg® as Re-induction Treatment in Patients With First Relapse of Acute Myeloid Leukemia

For several years, the effective standard induction chemotherapy for AML has been limited to the association of anthracycline and aracytine. GO is the first effective targeted antibody used in leukemia patients. In a previous study, we showed efficacy and safety of fractionated doses of GO used as a single agent for treatment of adult AML patients in first relapse. In the present study the possibility of combining fractionated doses of GO to escalated doses of a 3+7 regimen old is studied in relapsed AML patients > 50 and <70 years.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Mylotarg

Detailed Description

Induction course are:

GO 3mg/m2 on days 1, 4,7 + the three dose levels were as follows:

level 1: DNR: 45 mg/m2 x 3 days + AraC: 100 mg/m2 x 7 days level 2: DNR: 60 mg/m2 x 3 days + AraC: 100 mg/m2 x 7 days level 3: DNR 60 mg/m2 x 3 days + AraC: 200 mg/m2 x 7 days. with 20 mg of methylprednisolone prior to each GO infusion. Consolidation course: patients in CR may receive 2 additional courses of consolidation chemotherapy with Amsacrine 90 mg/m2 daily for 3 days, and Ara-C (1g/m2/12 hours x 3 days) + GO 3 mg/m2 on day 1.

Treatment with HSCT is offered at the discretion of the physician in charge of the patient. A delay between last infusion of GO and HSCT above 3 months is recommended

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bobigny, France
    • Hôpital Avicenne
  • Caen, France, 14033
    • CH
  • Clamart, France, 92141
    • Hôpital Percy
  • Creteil, France, 94010
    • CHU
  • Lille, France, 59037
    • CHU
  • Limoges, France, 87042
    • CH
  • Lyon, France
    • Hôpital Edouard Herriot
  • Meaux, France, 77104
    • CH
  • Paris, France
    • Hopital Saint-Louis
  • Paris, France, 75012
    • St Antoine Hospital
  • Roubaix, France, 59100
    • CH
  • Rouen, France, 76038
    • CHU
  • Saint-Cloud, France
    • CNLCC
  • Versailles, France
    • CH
  • Villejuif, France, 94805
    • IGR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with a morphologically proven diagnosis of CD33-positive AML and :

1. Age ≥ 50 years and ≤ 70 years.
2. First relapsing AML with a duration of first CR ≥ 3 and ≤18 months
3. ECOG performance status 0 to 3
4. Negative serology HIV, HBV and HBC (except post vaccination)
5. Serum creatinine ≤ 2N; AST and ALT ≤ 2N; total bilirubin ≤ 2N
6. Cardiac function determined by radionuclide or echography within normal limits.
7. Negative serum pregnancy test within one week before treatment for women of child bearing potential
8. Signed informed consent.

Exclusion Criteria:

1. M3-AML
2. AML following diagnosed myelodysplastic syndrome or myeloproliferation
3. Known central nervous system involvement with AML
4. Prior treatment with HSCT.
5. Previous treatment with Anti CD33 antibodies
6. Uncontrolled infection
7. Other active malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: DAUNORUBICINE - ARACYTINE - MYLOTARG -; Adaptive Bayesian method for dose-finding in phase I/II clinical trials based on treatment efficacy and toxicity (Thall, Russel, 1998), with successive patients cohorts and three combined dose levels: DNR 45 mg/m2 IV days 1 to 3 + AraC 100 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7. DNR 60 mg/m2 IV days 1 to 3 + AraC 100 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7. DNR 60 mg/m2 IV days 1 to 3 + AraC 200 mg/m2 CI days 1 to 7 + Mylotarg 3mg/m2 IV days 1, 4, 7. Two consolidation courses for CR patients: Amsacrine: 90 mg/m2 IV Day 1 Cytarabine: 1g/m2 twice a day IV Days 1 to 4 Mylotarg: 3 mg/m2 IV Day 1.

Drug: Mylotarg; Dose level study; Other Names: Gemtuzumab Ozogamicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-limiting toxicity (DLT) defined by the occurrence of any G3 or G4 non reversible toxicity at day 45 excluding myelosuppression or infection due to neutropenia, and response defined by complete remission at day 45	Day 45 post first dose of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary endpoint: Duration of second remission in AML patients treated for relapse with chemotherapy + Mylotarg as re-induction and consolidation.	At two years

Collaborators and Investigators

• Sponsor: Acute Leukemia French Association
• Investigators: Principal Investigator: CASTAIGNE SYLVIE, PROFESSOR, Acute Leukemia French Association

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: January 19, 2011
• First Submitted That Met QC Criteria: July 2, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 2, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; First relapsing AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Antineoplastic Agents, Immunological; Gemtuzumab
• Other Study ID Numbers: MYLOFRANCE 2