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

Sponsor

Acute Leukemia French Association (Other)

Overall Status

Completed

CT.gov ID

NCT02182596

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Mylotarg	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2006

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Avicenne	Bobigny	France
2	CH	Caen	France	14033
3	Hopital Percy	Clamart	France	92141
4	CHU	Creteil	France	94010
5	CHU	Lille	France	59037
6	CH	Limoges	France	87042
7	Hopital Edouard Herriot	Lyon	France
8	CH	Meaux	France	77104
9	St Antoine Hospital	Paris	France	75012
10	Hopital Saint-Louis	Paris	France
11	CH	Roubaix	France	59100
12	CHU	Rouen	France	76038
13	CNLCC	Saint-Cloud	France
14	CH	Versailles	France
15	IGR	Villejuif	France	94805