Acute Myeloid LeukemiaPhase 1/2NCT04112589

A Clinical Trial to Assess the Efficacy and Safety of the Combination of a Drug Call Quizartinib With Chemotherapy (FLAG-IDA) in Patients With Acute Myeloid Leukemia That Has Not Responded to the First Treatment or That Has Returned After the First Treatment

A Phase 1/2 study testing Quizartinib, Fludarabine and Cytarabine in people with Acute Myeloid Leukemia, run by PETHEMA Foundation at 20 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

Search all trials

Trial summary

This is a multicenter, prospective, non-randomized, Phase I-II trial to assess the efficacy and safety of the combination of oral quizartinib and FLAG-IDA chemotherapy schedule (FLAG-QUIDA regimen) in first relapsed/refractory AML (acute myeloid leukemia) patients. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Acute Myeloid Leukemia
What is being tested?: Quizartinib, Fludarabine and Cytarabine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 63 participants
Where: 20 sitesSpain
Study dates: 26 Dec 2019to Dec 2023
Phase: Phase 1/2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. Informed consent form must be signed by the patient and the Investigator.
Patients aged ≥ 18 years old and ≤70 years old at the time of screening.
First R/R AML defined as:
First relapse after frontline intensive chemotherapy (with or without prior alloSCT), irrespectively of the duration of the first CR. Patients previously treated with a FLT3 inhibitor different from quizartinib, can be included.
First refractory disease (defined as patients not achieving at least a PR after first induction cycle and/or not achieving CR/CRi after first 2 cycles). Patients previously treated with a FLT3 inhibitor different from quizartinib, can be included.
Non-APL AML.

Show all 15Show fewer

Considered for intensive approach as per Investigator judgment.
ECOG 0-2.
No contraindications for quizartinib.
No contraindications for intensive chemotherapy.
No severe organ function abnormalities.
No active relevant GVHD.
For the Phase II, FLT3-ITD patients will represent 50% of the study cohort (FLT3-TKD are not excluded but included in the FLT3-ITD-WT group).
Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception upon enrollment, during the treatment period and for 6 months following the last dose of investigational drug or cytarabine, whichever is later.
Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential) upon enrollment, during the treatment period, and for 6 months following the last dose of investigational drug or cytarabine, whichever is later.

Who cannot join

Patients with genetic diagnosis of acute promyelocytic leukemia.
Blastic phase of bcr/abl chronic myeloid leukemia.
Patients with other neoplastic disease, for whom the Investigator has clinical suspicion of active disease at the time of enrollment. Note: Patients with adequately treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia are eligible for this study. Hormonal or adjuvant therapies will be allowed for breast cancer or prostate cancer if they are on a stable dose for at least 2 weeks prior to first dose.
Presence of any severe psychiatric disease or physical condition/comorbidity that, according to the physician´s criteria, contraindicates the inclusion of the patient in the clinical trial
Serum creatinine ≥ 250 μmol/l (≥ 2.5 mg/dL) (unless it is attributable to AML activity).
Bilirubin, alkaline phosphatase, or SGOT >3 times the upper normal limit (unless it is attributable to AML activity).

Show all 28Show fewer

Uncontrolled or significant cardiovascular disease, including any of the following:
Symptomatic bradycardia of less than 50 beats per minute, unless the subject has a pacemaker.
QTcF >450 ms at screening. Note: QTcF will be derived from the mean of triplicate readings.
Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome)
History of clinically relevant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes).
History of second- (Mobitz II) or third-degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker).
History of uncontrolled angina pectoris or myocardial infarction within 6months prior to Screening.
History of New York Heart Association Class 3 or 4 heart failure.
Complete left bundle branch block.
Right bundle branch and left anterior hemiblock (bifascicular block)
Infarction (MI) within 3 months.
Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥ 110 mmHg
A previously known left ventricle ejection fraction <45%
Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral.
Active hepatitis B or hepatitis C infection.
Previously known and documented human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study).
Active acute or chronic GVHD requiring prednisone >10 mg or equivalent corticosteroid daily
Any patients with known significant impairment in gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of quizartinib
History of hypersensitivity to any excipients in the quizartinib tablets.
Females who are pregnant or breastfeeding.
Isolated extramedullary R/R AML.
Only applicable to patients screened after the first cohort of 34 patients of the Phase II has been achieved (e.g., FLT3-ITD negative): patients must have a confirmation of FLT3-ITD status at relapse, and this must correspond to the non-achieved cohort (e.g. FLT3-ITD positive).

Trial locations and contacts

20 sites in 1 country.

City, postcode or hospital

20 sites in 1 country

Spain20 sites

Complexo Hospitalario Universitario A Coruña
A Coruña
Hospital General Universitario de Alicante
Alicante
Institut Català D'Oncologia-Hospital Germans Trias I Pujol
Badalona
Institut Català D'Oncologia-Hospital Duran I Reynals
Bellvitge
Hospital San Pedro de Alcántara
Cáceres
Hospital Universitario Puerta Del Mar
Cadiz
Hospital Universitario Reina Sofía
Córdoba
ICO Girona - Hospital Josep Trueta
Girona
Hospital Universitario de Jerez de La Frontera
Jerez de la Frontera
Complejo Hospitalario de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria
Complejo Hospitalario Universitario Insular-Materno Infantil
Las Palmas de Gran Canaria
Hospital Ramón Y Cajal
Madrid
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario Virgen de La Victoria
Málaga
Hospital Universitario Central de Asturias
Oviedo
Hospital Universitari Son Espases
Palma de Mallorca
Clínica Universitaria de Navarra
Pamplona
Hospital Universitario Virgen Del Rocío
Seville
Hospital Universitari Joan Xxiii de Tarragona
Tarragona
Hospital Universitari i Politècnic La Fe
Valencia

Other trials in Spain

About this study

Official title: A Multicenter, Prospective, Non-randomized, Phase I-II Trial to Assess the Efficacy and Safety of the Combination of Oral Quizartinib and the FLAG-IDA Chemotherapy Regimen in First Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients

Read the detailed description

Patients of approximately 20 sites (in Spain and Portugal) will receive FLAG-QUIDA regimen followed by transplantation, when possible, with up to 3 optional consolidation cycles. All patients in CR/CRi (complete remission / complete remission with incomplete hematologic recovery) will receive a maintenance schedule.

A Phase I (dose escalation) will be performed at 40 mg x 14 days of quizartinib in the first 3 patients, and if no dose-limiting toxicity (DLT) is observed, the next cohort of patients will receive 60 mg x 14 days. There is also the possibility of de-escalation cohorts at 60 mg x 7 days and at 40 mg x 7 days. Patients participating in the Phase I will receive the allocated dose level, and therefore, they must not receive strong CYP3A4 inhibitors concomitantly with quizartinib The Phase II will include 68 patients treated at the RP2D (recommended phase 2 dose). A 1-year maintenance schedule starting at 30 mg will be increased to 60 mg/day if appropriate.

Patients will be followed up for a minimum period of 1 year since the first visit of the last patient included.

Conditions: Acute Myeloid Leukemia
Being tested: Quizartinib, Fludarabine, Cytarabine, Idarubicin, glycosylated G-CSF
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

QuizartinibDrug
Quizartinib at different doses in the phase I (40mg-14 days; 60mg-14 days; 60mg-7days, 40mg-7days). RP2D in the phase II part.
FludarabineDrug
30 mg/m2 intravenous days 1 to 4 of the cycle
CytarabineDrug
2 g/m 2 intravenous days 1 to 4 (1 g/m2 in patients older than 59) of the cycle
IdarubicinDrug
10 mg/ 2 intravenous days 1 to 3 of the cycle
glycosylated G-CSFDrug
daily dose of 300 mcg/m 2 , from day -1 until day 5 of the cycle

Study groups in NCT04112589
Study group	Role	What they receive
Level dose 1 - 40mg, 14 days	Experimental	Patients will receive an induction cycle (40mg Quizartinib for 14 days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate. Receives: Drug: Quizartinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Idarubicin; Drug: glycosylated G-CSF
Level dose 2 - 60mg, 14 days	Experimental	Patients will receive an induction cycle (60mg Quizartinib for 14 days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate. Receives: Drug: Quizartinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Idarubicin; Drug: glycosylated G-CSF
Level dose -1 - 60mg 7days	Experimental	Patients will receive an induction cycle (60mg Quizartinib for 7 days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate. Receives: Drug: Quizartinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Idarubicin; Drug: glycosylated G-CSF
Level dose -2 - 40mg 7 days	Experimental	Patients will receive an induction cycle (40mg Quizartinib for 7days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate. Receives: Drug: Quizartinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Idarubicin; Drug: glycosylated G-CSF

What is being measured

The primary outcome is the main question the study is designed to answer.

RP2D finding
Maximum Tolerated dose of the combination of quizartinib a FLAG-IDA regimen
Measured: 1 cycle (4 weeks)
Rate CR/CRi
To assess the rate of CR/CRi after one cycle of FLAG-QUIDA
Measured: 3 years

Secondary outcomes (2)

Disease-free survival (DFS)
time from the first documentation of remission to the documentation of disease recurrence or death
Measured: 3 years
Overall survival (OS)
Number of days from randomization until death from any cause
Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Dec 2019Dec 2023

First posted2 Oct 2019
Study start26 Dec 2019
Primary completionDec 2023 (estimated)
Study completionDec 2023 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (16)Papers the sponsor has linked to this study.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: The study consists of a dose escalation-dose finding part (phase I) and a phase II part. Subjects will have an induction of 1 cycle, by an alloSCT (allogeneic hematopoietic stem cell transplantation) in CR/CRi, when possible, with up to 3 optional HiDAC (high dose Cytarabine ) consolidation cycles. All patients in CR/CRi will receive a maintenance schedule (12 months, 12 cycles). The phase I portion will progress from starting level dose 1 (40mg 14 days) to level dose 2 (60 mg 14 days). De-escalation to level dose -1 (60mg 7 days) or level dose -2 (40mg 7 days) may be necessary to be explored. Once the RP2D is established, the phase II will start.
Masking: None (open label)
Enrolment: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04112589
Sponsor's protocol ID: FLAG-QUIDA
Status last verified: Mar 2022
First submitted: 30 Sep 2019
Last updated: 14 Mar 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.
PubMed 19880497
Forman SJ, Rowe JM. The myth of the second remission of acute leukemia in the adult. Blood. 2013 Feb 14;121(7):1077-82. doi: 10.1182/blood-2012-08-234492. Epub 2012 Dec 14.
PubMed 23243288
Estey EH. Treatment of relapsed and refractory acute myelogenous leukemia. Leukemia. 2000 Mar;14(3):476-9. doi: 10.1038/sj.leu.2401568.
PubMed 10720145
Yavuz S, Paydas S, Disel U, Sahin B. IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. Am J Ther. 2006 Sep-Oct;13(5):389-93. doi: 10.1097/01.mjt.0000181690.21601.09.
PubMed 16988532
Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. doi: 10.1007/s00277-003-0624-2. Epub 2003 Mar 15.
PubMed 12707726
de la Rubia J, Regadera A, Martin G, Cervera J, Sanz G, Martinez J, Jarque I, Garcia I, Andreu R, Moscardo F, Jimenez C, Molla S, Benlloch L, Sanz M. FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. Leuk Res. 2002 Aug;26(8):725-30. doi: 10.1016/s0145-2126(02)00003-6.
PubMed 12191567
Kim H, Park JH, Lee JH, Lee JH, Joo YD, Lee WS, Bae SH, Mo Ryoo H, Lee KH; Cooperative Study Group A for Hematology. Continuous infusion of intermediate-dose cytarabine and fludarabine with idarubicin for patients younger than 60 years with resistant acute myeloid leukemia: a prospective, multicenter phase II study. Am J Hematol. 2009 Mar;84(3):161-6. doi: 10.1002/ajh.21351.
PubMed 19195034
Bergua JM, Montesinos P, Martinez-Cuadron D, Fernandez-Abellan P, Serrano J, Sayas MJ, Prieto-Fernandez J, Garcia R, Garcia-Huerta AJ, Barrios M, Benavente C, Perez-Encinas M, Simiele A, Rodriguez-Macias G, Herrera-Puente P, Rodriguez-Veiga R, Martinez-Sanchez MP, Amador-Barciela ML, Riaza-Grau R, Sanz MA; PETHEMA group. A prognostic model for survival after salvage treatment with FLAG-Ida +/- gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol. 2016 Sep;174(5):700-10. doi: 10.1111/bjh.14107. Epub 2016 Apr 26.
PubMed 27118319
Cortes J, Perl AE, Dohner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Kramer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):889-903. doi: 10.1016/S1470-2045(18)30240-7. Epub 2018 May 31.
PubMed 29859851
Cortes JE, Kantarjian H, Foran JM, Ghirdaladze D, Zodelava M, Borthakur G, Gammon G, Trone D, Armstrong RC, James J, Levis M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013 Oct 10;31(29):3681-7. doi: 10.1200/JCO.2013.48.8783. Epub 2013 Sep 3.
PubMed 24002496
Cortes JE, Tallman MS, Schiller GJ, Trone D, Gammon G, Goldberg SL, Perl AE, Marie JP, Martinelli G, Kantarjian HM, Levis MJ. Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML. Blood. 2018 Aug 9;132(6):598-607. doi: 10.1182/blood-2018-01-821629. Epub 2018 Jun 6.
PubMed 29875101
Chen Y, Pan Y, Guo Y, Zhao W, Ho WT, Wang J, Xu M, Yang FC, Zhao ZJ. Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia. Stem Cell Investig. 2017 Jun 2;4:48. doi: 10.21037/sci.2017.05.04. eCollection 2017.
PubMed 28607922
Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. doi: 10.1200/JCO.2003.04.036.
PubMed 14673054
Creutzig U, Kaspers GJ. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2004 Aug 15;22(16):3432-3. doi: 10.1200/JCO.2004.99.116. No abstract available.
PubMed 15310791
Montesinos P, Lorenzo I, Martin G, Sanz J, Perez-Sirvent ML, Martinez D, Orti G, Algarra L, Martinez J, Moscardo F, de la Rubia J, Jarque I, Sanz G, Sanz MA. Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model. Haematologica. 2008 Jan;93(1):67-74. doi: 10.3324/haematol.11575.
PubMed 18166787

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

All Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Prospective, Non-randomized, Phase I-II Trial to Assess the Efficacy and Safety of the Combination of Oral Quizartinib and the FLAG-IDA Chemotherapy Regimen in First Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients
ClinicalTrials.gov ID: NCT04112589
Acronym / sponsor ID: FLAG-QUIDA
Conditions: Acute Myeloid Leukemia
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 63 participants (actual)
Lead sponsor: PETHEMA FoundationUniversity, hospital or other
Collaborators: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company, Syntax for Science, S.L
Study start: 26 Dec 2019 (actual)
Primary completion: Dec 2023 (estimated)
Study completion: Dec 2023 (estimated)
First posted: 2 Oct 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Patients will be followed up for a minimum period of 1 year since the first visit of the last patient included.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 4
Model description: The study consists of a dose escalation-dose finding part (phase I) and a phase II part. Subjects will have an induction of 1 cycle, by an alloSCT (allogeneic hematopoietic stem cell transplantation) in CR/CRi, when possible, with up to 3 optional HiDAC (high dose Cytarabine ) consolidation cycles. All patients in CR/CRi will receive a maintenance schedule (12 months, 12 cycles). The phase I portion will progress from starting level dose 1 (40mg 14 days) to level dose 2 (60 mg 14 days). De-escalation to level dose -1 (60mg 7 days) or level dose -2 (40mg 7 days) may be necessary to be explored. Once the RP2D is established, the phase II will start.

Arm	Type	Receives
Level dose 1 - 40mg, 14 days	Experimental	Drug: Quizartinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Idarubicin, Drug: glycosylated G-CSFPatients will receive an induction cycle (40mg Quizartinib for 14 days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate.
Level dose 2 - 60mg, 14 days	Experimental	Drug: Quizartinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Idarubicin, Drug: glycosylated G-CSFPatients will receive an induction cycle (60mg Quizartinib for 14 days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate.
Level dose -1 - 60mg 7days	Experimental	Drug: Quizartinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Idarubicin, Drug: glycosylated G-CSFPatients will receive an induction cycle (60mg Quizartinib for 7 days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate.
Level dose -2 - 40mg 7 days	Experimental	Drug: Quizartinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Idarubicin, Drug: glycosylated G-CSFPatients will receive an induction cycle (40mg Quizartinib for 7days) followed by 1-3 consolidation cycles (Quizartinib at day 6) [with or without allogenic stem cell transplantation]- Responders will have 12 months maintenance starting at 30mg/day Quizartinib will be increased to 60 mg/day after 15 days if appropriate.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. Informed consent form must be signed by the patient and the Investigator.
Patients aged ≥ 18 years old and ≤70 years old at the time of screening.
First R/R AML defined as:
Non-APL AML.
Considered for intensive approach as per Investigator judgment.

Key exclusion criteria (28 listed)

Patients with genetic diagnosis of acute promyelocytic leukemia.
Blastic phase of bcr/abl chronic myeloid leukemia.
Patients with other neoplastic disease, for whom the Investigator has clinical suspicion of active disease at the time of enrollment. Note: Patients with adequately treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia are eligible for this study. Hormonal or adjuvant therapies will be allowed for breast cancer or prostate cancer if they are on a stable dose for at least 2 weeks prior to first dose.
Presence of any severe psychiatric disease or physical condition/comorbidity that, according to the physician´s criteria, contraindicates the inclusion of the patient in the clinical trial
Serum creatinine ≥ 250 μmol/l (≥ 2.5 mg/dL) (unless it is attributable to AML activity).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
QuizartinibQuizartinib at different doses in the phase I (40mg-14 days; 60mg-14 days; 60mg-7days, 40mg-7days). RP2D in the phase II part.	Drug	Level dose -1 - 60mg 7days, Level dose -2 - 40mg 7 days, Level dose 1 - 40mg, 14 days, Level dose 2 - 60mg, 14 days
Fludarabine30 mg/m2 intravenous days 1 to 4 of the cycle	Drug	Level dose -1 - 60mg 7days, Level dose -2 - 40mg 7 days, Level dose 1 - 40mg, 14 days, Level dose 2 - 60mg, 14 days
Cytarabine2 g/m 2 intravenous days 1 to 4 (1 g/m2 in patients older than 59) of the cycle	Drug	Level dose -1 - 60mg 7days, Level dose -2 - 40mg 7 days, Level dose 1 - 40mg, 14 days, Level dose 2 - 60mg, 14 days
Idarubicin10 mg/ 2 intravenous days 1 to 3 of the cycle	Drug	Level dose -1 - 60mg 7days, Level dose -2 - 40mg 7 days, Level dose 1 - 40mg, 14 days, Level dose 2 - 60mg, 14 days
glycosylated G-CSFdaily dose of 300 mcg/m 2 , from day -1 until day 5 of the cycle	Drug	Level dose -1 - 60mg 7days, Level dose -2 - 40mg 7 days, Level dose 1 - 40mg, 14 days, Level dose 2 - 60mg, 14 days

Primary outcome

RP2D finding
Time frame: 1 cycle (4 weeks)
Maximum Tolerated dose of the combination of quizartinib a FLAG-IDA regimen
Rate CR/CRi
Time frame: 3 years
To assess the rate of CR/CRi after one cycle of FLAG-QUIDA

2 secondary outcomes

Disease-free survival (DFS)
Time frame: 3 years
Overall survival (OS)
Time frame: 3 years

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2022.
Background: PubMed 19880497Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.
Background: PubMed 23243288Forman SJ, Rowe JM. The myth of the second remission of acute leukemia in the adult. Blood. 2013 Feb 14;121(7):1077-82. doi: 10.1182/blood-2012-08-234492. Epub 2012 Dec 14.
Background: PubMed 10720145Estey EH. Treatment of relapsed and refractory acute myelogenous leukemia. Leukemia. 2000 Mar;14(3):476-9. doi: 10.1038/sj.leu.2401568.
Background: PubMed 16988532Yavuz S, Paydas S, Disel U, Sahin B. IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. Am J Ther. 2006 Sep-Oct;13(5):389-93. doi: 10.1097/01.mjt.0000181690.21601.09.
Background: PubMed 12707726Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. doi: 10.1007/s00277-003-0624-2. Epub 2003 Mar 15.
Background: PubMed 12191567de la Rubia J, Regadera A, Martin G, Cervera J, Sanz G, Martinez J, Jarque I, Garcia I, Andreu R, Moscardo F, Jimenez C, Molla S, Benlloch L, Sanz M. FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. Leuk Res. 2002 Aug;26(8):725-30. doi: 10.1016/s0145-2126(02)00003-6.
Background: PubMed 19195034Kim H, Park JH, Lee JH, Lee JH, Joo YD, Lee WS, Bae SH, Mo Ryoo H, Lee KH; Cooperative Study Group A for Hematology. Continuous infusion of intermediate-dose cytarabine and fludarabine with idarubicin for patients younger than 60 years with resistant acute myeloid leukemia: a prospective, multicenter phase II study. Am J Hematol. 2009 Mar;84(3):161-6. doi: 10.1002/ajh.21351.
Background: PubMed 27118319Bergua JM, Montesinos P, Martinez-Cuadron D, Fernandez-Abellan P, Serrano J, Sayas MJ, Prieto-Fernandez J, Garcia R, Garcia-Huerta AJ, Barrios M, Benavente C, Perez-Encinas M, Simiele A, Rodriguez-Macias G, Herrera-Puente P, Rodriguez-Veiga R, Martinez-Sanchez MP, Amador-Barciela ML, Riaza-Grau R, Sanz MA; PETHEMA group. A prognostic model for survival after salvage treatment with FLAG-Ida +/- gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol. 2016 Sep;174(5):700-10. doi: 10.1111/bjh.14107. Epub 2016 Apr 26.
Background: PubMed 29859851Cortes J, Perl AE, Dohner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Kramer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):889-903. doi: 10.1016/S1470-2045(18)30240-7. Epub 2018 May 31.
Background: PubMed 24002496Cortes JE, Kantarjian H, Foran JM, Ghirdaladze D, Zodelava M, Borthakur G, Gammon G, Trone D, Armstrong RC, James J, Levis M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013 Oct 10;31(29):3681-7. doi: 10.1200/JCO.2013.48.8783. Epub 2013 Sep 3.
Background: PubMed 29875101Cortes JE, Tallman MS, Schiller GJ, Trone D, Gammon G, Goldberg SL, Perl AE, Marie JP, Martinelli G, Kantarjian HM, Levis MJ. Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML. Blood. 2018 Aug 9;132(6):598-607. doi: 10.1182/blood-2018-01-821629. Epub 2018 Jun 6.
Background: PubMed 28607922Chen Y, Pan Y, Guo Y, Zhao W, Ho WT, Wang J, Xu M, Yang FC, Zhao ZJ. Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia. Stem Cell Investig. 2017 Jun 2;4:48. doi: 10.21037/sci.2017.05.04. eCollection 2017.
Individual participant dataSharing planned: No

Related trials for Acute Myeloid Leukemia

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pau Montesinos, MD study director

Trial Coordinator, Institution Contact

20 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Quizartinib, Fludarabine and Cytarabine in people with Acute Myeloid Leukemia, run by PETHEMA Foundation at 20 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

RP2D finding (time frame: 1 cycle (4 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04112589, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2022.