Informations générales (source: ClinicalTrials.gov)
AGORA-1 /ALFA 2100 Study : A Phase 2 Study of Gemtuzumab Ozogamicin (GO)-Gilteritinib Combination in Adults With FLT3-ITD Relapse/Refractory (R/R) AML (AGORA-1)
Interventional
Phase 2
Centre Antoine Lacassagne (Voir sur ClinicalTrials)
juin 2023
mars 2027
29 juin 2024
This is a national, open-label, single-arm, multicenter phase II trial evaluating the
safety and efficacy of adding gilteritinib, a new FLT3 inhibitor to the AGORA platform,
consisting of the combination of an intermediate dose of cytarabine and a divided dose of
GO in adult patients with R / R AML with an FLT3-ITD mutation.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| HOPITAL NOVO | VAIDA | 04/07/2024 11:04:55 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Avicenne | Thorsten BRAUN | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Necker-Enfants Malades | Ambroise MARCAIS | Contact (sur clinicalTrials) | |||
| CH DE VERSAILLES SITE ANDRE MIGNOT | Juliette LAMBERT | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Henri Becquerel - Rouen - France | Emilie LEMASLE | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - Lyon - France | Amine BELHABRI | Contact (sur clinicalTrials) | |||
| CH de Meaux - Meaux - France | Jamilé FRAYFER | Contact (sur clinicalTrials) | |||
| CH Victor Dupouy - Argenteuil - France | Ahmad AL JIJAKLI | Contact (sur clinicalTrials) | |||
| CHMS de Chambery - Chambery - France | Gian-Matteo PICA | Contact (sur clinicalTrials) | |||
| CHR Orléans - Orléans - France | Magda ALEXIS | Contact (sur clinicalTrials) | |||
| CHRU Bretonneau - Tours - France | Alban VILLATE | Contact (sur clinicalTrials) | |||
| CHRU Nancy - Nancy - France | Caroline BONMATI | Contact (sur clinicalTrials) | |||
| CHU Bordeaux - Bordeaux - France | Pierre-Yves DUMAS | Contact (sur clinicalTrials) | |||
| CHU d'Amiens - Amiens - France | Delphine LEBON | Contact (sur clinicalTrials) | |||
| CHU d'Angers - Angers - France | Mathilde HUNAULT | Contact (sur clinicalTrials) | |||
| CHU de Caen - Caen - France | Sylvain CHANTEPIE | Contact (sur clinicalTrials) | |||
| CHU Dijon - Dijon - France | Ingrid LAFON | Contact (sur clinicalTrials) | |||
| CHU Henri Mondor - Créteil - France | Cécile PAUTAS | Contact (sur clinicalTrials) | |||
| CHU Limoges - Limoges - France | Arnaud JACCARD | Contact (sur clinicalTrials) | |||
| CHU Nantes - Nantes - France | Pierre PETERLIN | Contact (sur clinicalTrials) | |||
| CHU Poitiers - Poitiers - France | Maria GALLEGO | Contact (sur clinicalTrials) | |||
| CHU Pontchaillou - Rennes - France | Marc BERNARD | Contact (sur clinicalTrials) | |||
| CHU Robert Debré - Reims - France | Chantal HIMBERLIN | Contact (sur clinicalTrials) | |||
| HIA Percy - Clamart - France | Pierre ARNAUTOU | Contact (sur clinicalTrials) | |||
| Hôpital de la Pitié Salpétrière - Paris - France | Madalina UZUNOV | Contact (sur clinicalTrials) | |||
| Hôpital la Timone Conception - Marseille - France | Régis COSTELLO | Contact (sur clinicalTrials) | |||
| Hôpital Lyon sud - Lyon - France | Maël HEIBLIG | Contact (sur clinicalTrials) | |||
| Hôpital Saint Louis - Paris - France | Emmanuel RAFFOUX | Contact (sur clinicalTrials) | |||
| IGR - Villejuif - France | Jean-Baptiste MICOL | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Patients aged 18 years old or more
- Confirmed diagnosis of R/R AML positive for CD33 antigen as determined locally by
immunophenotyping according to routine practice, defined as:
- AML refractory to 1 or 2 intensive chemotherapy courses or a treatment by
hypomethylating agents (HMAs)
- Or AML in first hematologic relapse or progression after front-line therapy,
including intensive chemotherapy or hypomethylating agents (HMAs).
- Previous treatments with FLT3 inhibitors (other than gilteritinib) are allowed
- R/R AML secondary to a prior chemotherapy or radiotherapy for another cancer
(tAML) could be included.
- Presence of a FLT3-ITD mutation (allelic ratio ≥0.05 at last evaluation)* or a FLT3
TKD mutation
- Patient with no contraindication to gemtuzumab ozogamicin (GO), cytarabine and
gilteritinib
- ECOG performance status ≤2
- AST and ALT ≤ 2.5 x upper the limit of normal (ULN) and/or total and direct serum
bilirubin ≤ 1.5 x ULN unless considered due to leukemia
- Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the formula
usually used by the investigator
- Written informed consent obtained prior to any screening procedures
- Eligible for National Health Insurance in France
- Patients aged 18 years old or more
- Confirmed diagnosis of R/R AML positive for CD33 antigen as determined locally by
immunophenotyping according to routine practice, defined as:
- AML refractory to 1 or 2 intensive chemotherapy courses or a treatment by
hypomethylating agents (HMAs)
- Or AML in first hematologic relapse or progression after front-line therapy,
including intensive chemotherapy or hypomethylating agents (HMAs).
- Previous treatments with FLT3 inhibitors (other than gilteritinib) are allowed
- R/R AML secondary to a prior chemotherapy or radiotherapy for another cancer
(tAML) could be included.
- Presence of a FLT3-ITD mutation (allelic ratio ≥0.05 at last evaluation)* or a FLT3
TKD mutation
- Patient with no contraindication to gemtuzumab ozogamicin (GO), cytarabine and
gilteritinib
- ECOG performance status ≤2
- AST and ALT ≤ 2.5 x upper the limit of normal (ULN) and/or total and direct serum
bilirubin ≤ 1.5 x ULN unless considered due to leukemia
- Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the formula
usually used by the investigator
- Written informed consent obtained prior to any screening procedures
- Eligible for National Health Insurance in France
- Acute promyelocytic leukemia or AML with BCR-ABL1 gene fusion
- Secondary AML (sAML) defined by a history of prior myelodysplastic syndrome (MDS) or
myeloproliferative syndrome (MPN) including chronic myelomonocytic leukemia (CMML)
- Patient with contraindications to the administration of gemtuzumab ozogamicin (GO),
cytarabine and gilteritinib. Refer to the SPCs of the molecules mentioned concerning
the contraindications, special warnings, precautions for use, dose modifications in
the event of toxicity, contraception and monitoring of patients and drugs prohibited
or to be used with caution.
- Proven central nervous system leukemic involvement
- Prior allogeneic HSCT within the last 6 months and/or history of acute GVHD of grade
>1
- Prior treatment with gemtuzumab ozogamicin within the last 3 months preceding the
initiation of the treatment in the present clinical trial
- Uncontrolled or active malignant disease within prior 12 months (excluding cutaneous
basal cell carcinoma, "in-situ" carcinoma of the cervix or breast, or other local
malignancy excised)
- Uncontrolled or significant cardiovascular history or symptoms including:
- Prior anthracycline exposure equivalent to more than 550 mg/m2 of daunorubicin
- History of clinically relevant ventricular arrhythmias (e.g. ventricular
tachycardia, ventricular fibrillation or torsade de pointes)
- History of 2° (Mobitz II) or 3° heart block (subjects with pacemakers are
allowed if they have no history of clinically relevant arrhythmias with the
pacemaker)
- History of uncontrolled angina pectoris or MI within 6 months
- History of NYHA Class 3 or 4 heart failure
- Left ventricular ejection fraction ≤ 50% or less than the institutional lower
limit of normal
- History of complete left bundle branch block
- Unstable angina, New York Heart Association (NYHA) class 3 or 4 congestive
heart failure
- QTcF > or equal to 450 msec, long QT syndrome (including family history)
- Bradycardia < 50 bpm (unless subject has a pacemaker)
- Systolic BP ≥ 180 mmHg or diastolic BP ≥ 110 mmHg
- Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing
signs/symptoms related to the infection without improvement despite appropriate
treatment)
- Active known HBV or HCV hepatitis or positive HIV serology
- Concurrent therapy with any other investigational agent or cytotoxic drug, within 28
days before starting treatment. Only hydroxyurea ± dexamethasone is permitted for
the control of blood counts
- Current use or anticipated requirement for drugs that are known strong inducers of
CYP3 A4/5
- Current use or anticipated requirement for drugs that are known as strong inhibitors
or inducers of P glycoprotein (P-gp), as mentioned in the appendix 14 of the
protocol, with the exception of drugs that are considered absolutely essential for
the care of the subject
- Current use or anticipated treatment with concomitant drugs that target 5HT1R or
5HT2BR receptors or sigma non-specific receptor, as mentioned in the appendix 15 of
the protocol, with exception of drugs that are considered absolutely essential for
the care of the subject
- Known malabsorption syndrome or other condition that may significantly impair
absorption of oral study medications
- Any of concurrent severe and/or uncontrolled medical condition, which could
compromise participation in the study.
- Patient currently receiving one or more inadvisable or prohibited treatments
described in section 6.4.2 of the protocol.
- Females who are pregnant or breastfeeding.
- Women of childbearing potential or partners of women of childbearing potential
should use a highly effective method of contraception during treatment and change
the duration of contraception after the last dose of the medicines of the study (GO,
cytarabine and gilteritinib).
- For women of childbearing potential (WOCBP): agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraception with a failure
rate of < 1% per year during the treatment period and after the final dose of
study treatment for at least: - 7 months for GO, - 6 months for cytarabine, - 6
months for gilteritinib. Women must refrain from donating eggs during this same
period. A woman is considered to be of childbearing potential if she is
postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months
of amenorrhea with no identified cause other than menopause), and has not
undergone surgical sterilization is permanently infertile due to surgery (i.e.
removal of ovaries, fallopian tubes, and/or uterus) or another cause as
determined by the investigator (e.g., Müllerian agenesis). The definition of
childbearing potential may be adapted for alignment with local guidelines or
regulations. Examples of contraceptive methods with a failure rate of < 1% per
year include bilateral tubal ligation, male sterilization, hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices,
and copper intrauterine devices. Hormonal contraceptive methods must be
supplemented by a barrier method. The reliability of sexual abstinence should
be evaluated in relation to the duration of the clinical trial and the
preferred and usual lifestyle of the patient. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, or postovulation methods) and withdrawal
are not acceptable methods of contraception. If required per local guidelines
or regulations, locally recognized acceptable methods of contraception and
information about the reliability of abstinence will be described in the local
Informed Consent Form. Women of childbearing potential must have a negative
serum pregnancy test result within 7 days prior to first dose.
- For male patients: acceptance that most of the study treatments require
specific reliable and effective contraception measures, as well as measures
related to sperm donation Agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception, and agreement to refrain from
donating sperm, as defined below With a female partner of childbearing
potential who is not pregnant, men who are not surgically sterile must remain
abstinent or use a condom plus an additional contraceptive method that together
result in a failure rate of < 1% per year during the treatment period and after
the final dose of study treatment for at least: - 4 months for GO, - 6 months
for cytarabine, - 4 months for gilteritinib.
Men must refrain from donating sperm during this same period With pregnant female
partners, men must remain abstinent or use a condom to avoid exposing the embryo during
the treatment period and for at least: - 4 months for GO, - 6 months for cytarabine, - 4
months for gilteritinib. The reliability of sexual abstinence should be evaluated in
relation to the duration of the clinical trial and the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of contraception. If
required per local guidelines or regulations, locally recognized acceptable methods of
contraception and information about the reliability of abstinence will be described in
the local Informed Consent Form.
- Adults subject to a legal protection order or unable to give their consent
- Persons deprived of their freedom by judicial or administrative decision, persons
hospitalized without their consent by virtue of articles L. 3212-1 and L. 3213-1 and
who are not subject to the provisions of article L. 1121-8.