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AzTrials

Leukemia, Myeloid, AcutePhase 3PEVOLAMNCT04090736

Study to Compare Azacitidine Plus Pevonedistat Versus Azacitidine in Patients With Acute Myeloid Leukemia Not Eligible for Standard Chemotherapy

A Phase 3 study testing Pevonedistat and Azacitidine in people with Leukemia, Myeloid, Acute, run by PETHEMA Foundation at 62 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Randomized phase III, multicentre, open label clinical trial to compare pevonedistat in combination with azacytidine versus azacytidine alone, which can be considered a standard of care for patients with newly diagnosed acute myeloid leukemia not eligible for intensive chemotherapy (thus not eligible for an allogeneic… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myeloid, Acute
What is being tested?
Pevonedistat and Azacitidine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
302 participants
Where
62 sitesSpain
Study dates
24 Sep 2019to 30 Jul 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients 18 years or older
  • Morphological diagnosis of Acute Myeloid Leukemia (AML) (WHO criteria 2008)
  • Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 3 (ECOG 0-2 for patients greater than or equal to 75 years old).
  • Newly diagnosed AML
  • Patient must be considered be ineligible for treatment with a standard Ara-C and anthracycline induction regimen due to age or co-morbidities defined by one of the following:
  • ≥ 75 years of age
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  • Or ≥ 18 to 74 years of age with at least one of the following:
  • ECOG Performance Status of 2 or 3;
  • Cardiac history of cardiac heart failure requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina;
  • Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) ≤ 65% or Forced Expiratory Volume in 1 second (FEV1) ≤ 65% or significant history of chronic pulmonary obstructive disease;
  • Glomerular filtration rate (GFR) ≥ 30 mL/min to < 50 ml/min or levels of creatinine between the upper limit of the normal range (ULN) and 2.5 mg/dL (≤ 250 μmol/l).
  • Hepatic impairment with total bilirubin > 1.5 to ≤ 3 × ULN or with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5×ULN to ≤ 5×ULN
  • Non active/controlled prior neoplastic disease
  • Any other patient´s comorbidity or disease condition that the physician judges to be incompatible with intensive chemotherapy must be reviewed, documented, and approved by the Sponsor before study enrollment).
  • Clinical laboratory values within the following parameters (repeat within 3 days before the first dose of study drug if laboratory values used for randomization were obtained more than 3 days before the first dose of study drug):
  • Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome or ≤ 3 × ULN if elevation is attributed to underlying leukemia. Patients with Gilbert's syndrome may enroll with direct bilirubin ≤3 × ULN of the direct bilirubin. Elevated indirect bilirubin due to posttransfusion hemolysis is allowed.
  • ALT and AST ≤ 2.5×ULN or ≤ 5×ULN if elevation is attributed to underlying leukemia.
  • Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min (calculated by the Cockcroft Gault formula, (see Appendix 5).
  • Albumin >2.7 g/dL.
  • Subject has a white blood cell count <50 × 109/L. Patients who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility criteria before starting therapy.
  • Female subjects must be either postmenopausal for at least 1 year before screening (see Appendix 12 for definition) OR permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) OR Women of Childbearing Potential (WOCBP) must agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception (see Appendix 11), at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception). Female subjects of childbearing potential must have negative results for pregnancy test performed and must not be lactating and breastfeeding.
  • Male subjects even if surgically sterilized (i.e., status post vasectomy), who are sexually active, must agree, from Study Day 1 through at least 4 months after the last dose of study drug, to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
  • Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Who cannot join

  • Previous treatment for myelodysplastic síndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) or myeloproliferative neoplasms (MPN), with chemotherapy or other antineoplastic agents including HMAs (up to 2 cycles of Hypomethylating agents (HMA) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug.
  • Subject has history MPN with BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
  • Genetic diagnosis of acute promyelocytic leukemia.
  • Eligible for intensive chemotherapy and/or allogeneic stem cell transplantation.
  • The reason a patient is not eligible for intensive chemotherapy and/or allogeneic stem cell transplantation is described in the inclusion criteria section
  • The reason a patient is not eligible for intensive chemotherapy must be documented in the electronic case report form (eCRF).
Show all 31Show fewer
  • Patients with either clinical evidence of or history of central nervous system involvement by AML.
  • Diagnosed or treated for another malignancy within 1 year before randomization or previously diagnosed with another malignancy and have any evidence of residual disease which may compromise the administration of AZA or AZA+PEVO.
  • Psychological,social, or geographic factors that otherwise preclude the patient from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up.
  • Subject has a white blood cell count > 50 × 109/L.
  • Contraindications for PEVO or AZA.
  • Known hypersensitivity to pevonedistat or its excipients.
  • Female patients who intend to donate eggs (ova) during the course of this study or for 4 months after receiving their last dose of study drug(s).
  • Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
  • Male patients who intend to donate sperm or father a child during the course of this study or for 4 months after receiving their last dose of study drug(s).
  • Subject is known to be positive for HIV (HIV testing is not required for eligibility assessment). Known HIV positive patients who meet the following criteria will be considered eligible:
  • Cluster of differentiation 4 (CD4) count > 350 cells/mm3
  • Undetectable viral load
  • Maintained on modern therapeutic regimens utilizing non-cytochrome P450 (CYP)-interactive agents
  • No history of AIDS-defining opportunistic infections
  • Subject is known to be positive for hepatitis B or C infection, with the exception of those with an undetectable viral load within 3 months (Hepatitis B or C testing is not required for eligibility assessment).
  • Known hepatic cirrhosis or severe preexisting hepatic impairment.
  • Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV; see Appendix 7), and/or ST elevation myocardial infarction within 6 months before first dose, or severe symptomatic pulmonary hypertension requiring pharmacologic therapy, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. As an example, well-controlled atrial fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would be an exclusion. Patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled.
  • Subject has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.
  • Treatment with strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers (see Appendix 8) within 14 days before the first dose of pevonedistat.
  • Patients with uncontrolled coagulopathy or bleeding disorder.
  • High blood pressure which cannot be controlled by standard treatments
  • Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to institutional guidelines.
  • As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control and no signs of systemic inflammatory response beyond low grade fever that makes patient clinically unstable in the opinion of the investigator. Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control.
  • Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent and until toxicity from this has resolved to grade 1 or less; if the half-life of the agent is unknown, patients must wait 4 weeks prior to first dose of study treatment.
  • Systemic antineoplastic therapy for malignant conditions other than myeloid neoplasms within 14 days before the first dose of any study drug.

Trial locations and contacts

62 sites in 1 country.

62 sites in 1 country

Spain62 sites

  • Complejo Hospitalario Universitario A Coruña

    A Coruña, 15006

  • Complejo Hospitalario Universitario de Albacete

    Albacete, 02006

  • Hospital General Universitario de Alicante

    Alicante, 03010

  • Complejo Hospitalario Torrecárdenas

    Almería, 04004

  • Hospital Dr. José Molina Orosa

    Arrecife

  • Complejo Asistencial de Ávila

    Ávila

  • Hospital San Agustin

    Avilés

  • Hospital Universitario de Badajoz

    Badajoz

  • ICO Badalona- Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitario de Cruces

    Barakaldo, Vizcaya, 48903

  • Hospital del Mar

    Barcelona

  • Hospital Vithas Xanit Internacional

    Benalmádena

  • Hospital Universitario de Basurto

    Bilbao, Vizcaya, 48013

  • Hospital Universitario de Burgos

    Burgos, 09006

  • Complejo Hospitalario de Cáceres

    Cáceres, 10003

  • Hospital Universitario Puerta del Mar

    Cadiz, 11009

  • Hospital General Universitario Santa Lucía

    Cartagena, Murcia, 30200

  • Hospital General Universitario de Castellón

    Castelló

  • Complejo Hospitalario Regional Reina Sofía

    Córdoba, 14004

  • Hospital General Universitario de Elche

    Elche

  • Hospital Universitario de Galdakao

    Galdakao, Vizcaya, 48960

  • ICO Girona- Hospital Universitari Dr Josep Trueta

    Girona, 17007

  • Hospital Universitario de Guadalajara

    Guadalajara

  • ICO Hospitalet- Hospital Duran i Reynals

    Hospitalet Del Llobregat, Barcelona, 08908

  • Hospital Universitario Juan Ramón Jiménez

    Huelva, 21005

  • Hospital San Jorge

    Huesca

  • Complejo Hospitalario de Jaén

    Jaén, Jaen, 23007

  • Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria, Las Palmas, 35020

  • Complejo Hospitalario Lucus Augusti

    Lugo

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Madrid Norte Sanchinarro

    Madrid, 28050

  • Hospital Regional Universitario de Málaga

    Málaga, Malaga, 29010

  • Hospital Universitario Virgen de la Victoria

    Málaga, Malaga, 29010

  • Hospital Quirón de Málaga

    Málaga

  • Hospital General Universitario Morales Meseguer

    Murcia, 30008

  • Complexo Hospitalario Universitario de Ourense

    Ourense, 32005

  • Hospital Universitario Central de Asturias

    Oviedo, Principality of Asturias, 33006

  • Hospital Son Llàtzer

    Palma de Mallorca

  • Complexo Hospitalario de Pontevedra

    Pontevedra, 36071

  • Hospital Universitario Quirón Madrid

    Pozuelo de Alarcón, Madrid, 28223

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna, Santa Cruz De Tenerife

  • Hospital Universitario Donostia

    San Sebastián, Guipuzcoa

  • Hospital Universitario Infanta Sofía

    San Sebastián de los Reyes, Madrid, 28702

  • Complejo Hospitalario Universitario Nuestra Señora de la Candelaria

    Santa Cruz de Tenerife, 38010

  • Complejo Hospitalario Universitario de Santiago

    Santiago de Compostela, A Coruña, 15706

  • Hospital General de Segovia

    Segovia

  • Hospital Universitario Virgen del Rocío

    Seville, Sevila, 41013

  • Hospital de Valme

    Seville

  • Hospital General Nuestra Señora del Prado

    Talavera de la Reina, Toledo, 45600

  • Hospital Universitari Joan XXIII

    Tarragona, 43005

  • Hospital Virgen de la Salud

    Toledo

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Hospital Universitario Dr. Peset Aleixandre

    Valencia, 46017

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

  • Hospital Clínico Universitario de Valladolid

    Valladolid, 47003

  • Hospital Txagorritxu

    Vitoria-Gasteiz, Alava, 01009

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, 50009

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: A Randomized Phase III, Multicentre, Open Label Clinical Trial Comparing Azacitidine Plus Pevonedistat Versus Azacitidine in Older/Unfit Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Chemotherapy

Randomized phase III, multicentre, open label clinical trial to compare pevonedistat in combination with azacytidine versus azacytidine alone, which can be considered a standard of care for patients with newly diagnosed acute myeloid leukemia not eligible for intensive chemotherapy (thus not eligible for an allogeneic hematopoietic stem cell transplant.

Read the detailed description

Prospective, 1:1 randomized multicentre, open label, phase III clinical trial to evaluate efficacy and safety of pevonedistat in combination with azacytidine versus azacytidine in the treatment of naïve adult patients with acute myeloid leukemia who are not eligible for standard induction therapy due to age, co-morbidities or risk-factors.

Subjects will be randomized to one of the two treatment arms in a 1:1 ratio, both of which will have treatment cycles of 28 days:

  • Arm A: Pevonedistat (PEVO) 20 mg/m2 IV on days 1, 3, and 5 plus Azacitidine (AZA) 75 mg/m2 subcutaneous (SC) administered on a 5-on/2-off [weekend]/2-on schedule in 28-day cycles (IV AZA can be administered for any patients who have non-tolerated local reactions)
  • Arm B: AZA 75 mg/m2 SC on a 5-on/2-off [weekend]/2-on schedule in 28-day cycle (IV AZA can be administered for any patients who have non-tolerated local reactions) 466 subjects will be randomized in the study. Subjects will continue their study treatment until documented disease progression per Investigator assessment, unacceptable toxicity, withdrawal of consent, or the subject meets other protocol criteria for discontinuation
Being tested
Pevonedistat, Azacitidine
Keywords
Leukemia, Myeloid, Acute, Pevonedistat, Azacitidine, Randomized, Clinical trial
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia

What participants receive

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

  • PevonedistatDrug

    Pevonedistat 20 mg/m2 intravenous on days 1, 3, and 5 (28-day cycles)

  • AzacitidineDrug

    Azacitidine 75 mg/m2 subcutaneous on a 5-on/2-off [weekend]/2-on schedule (28-day cycle). Intravenous for patients who have non-tolerated local reactions

Study groups in NCT04090736
Study groupRoleWhat they receive
Arm A: Pevonedistat plus AzacitidineExperimentalPevonedistat 20 mg/m2 IV on days 1, 3, and 5 plus Azacitidine 75 mg/m2 subcutaneous administered on a 5-on/2-off [weekend]/2-on schedule in 28-day cycles (intravenous Azacitidine can be administered for any patients who have non-tolerated local reactions)
Receives: Drug: Pevonedistat; Drug: Azacitidine
Arm B: AzacitidineActive comparatorAzacitidine 75 mg/m2 subcutaneous on a 5-on/2-off [weekend]/2-on schedule in 28-day cycle (intravenous azacitidine can be administered for any patients who have non-tolerated local reactions)
Receives: Drug: Azacitidine

What is being measured

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

  1. Overall survival (OS)

    Time from the date of randomization to the date of death.

    Measured: through study completion, an average of 1 year

Secondary outcomes (25)

  1. Event-free survival (EFS)

    Time from randomization to the date of the occurrence of any of the following events: progressive disease, failure to achieve complete response or complete remission with incomplete blood count recovery at 6 months after initiation of treatment, relapse from complete response (CR)/ incomplete complete response (CRi) or death from any cause, whichever occurs first

    Measured: through study completion, an average of 1 year

  2. Composite complete remission

    The proportion of subjects with complete response plus complete remission with incomplete blood count recovery

    Measured: through study completion, an average of 1 year

  3. Overall response rate

    The proportion of subjects with complete response plus complete remission with incomplete blood count recovery plus partial response

    Measured: through study completion, an average of 1 year

  4. Cumulative incidence of relapse

    Calculated using the competing risk method (Fine \& Gray)

    Measured: through study completion, an average of 1 year

  5. Health status/quality of life

    Global health status/quality of life based on patient reported outcome EORTC Quality of life questionnaire (QLQ)-C30 and supplemental items.

    Measured: through study completion, an average of 1 year

  6. Health status/quality of life

    Global health status/quality of life based on patient reported outcome: EQ-5D-5L questionnaire.

    Measured: through study completion, an average of 1 year

  7. Use of medical resources determined by the use of antibiotics

    Compare the use of antibiotics during the study between treatment groups

    Measured: through study completion, an average of 1 year

  8. Use of medical resources determined by the use of transfusions

    Compare the use of transfusions during the study between treatment groups

    Measured: through study completion, an average of 1 year

  9. Use of medical resources determined by the number of hospital admissions

    Compare the number of hospital admissions during the study between treatment groups

    Measured: through study completion, an average of 1 year

  10. Pharmacokinetic

    Plasma concentration of Pevonedistat

    Measured: At day 1, 3 and 5 of cycle 1, cycle 2 and cycle 3 (each cycle is 28 days)

  11. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

    Adverse events of Pevonedistat plus Azacitidine versus Azacitidine regimen

    Measured: through study completion (an average of 1 year)

  12. Quality of composite complete remission determined by the minimal residual disease determined by RT-qPCR in the NPM1+ and CBF subsets and in bone marrow by MPFC in the remaining patients

    To evaluate the quality of composite complete remission determining the minimal residual disease in patients with complete remission and complete remission with incomplete blood count recovery

    Measured: through study completion, an average of 1 year

  13. Overall survival based on somatic mutations

    To explore relationship of somatic mutations at baseline with overall survival

    Measured: through study completion, an average of 1 year

  14. Event free survival based on somatic mutations

    To explore relationship of somatic mutations at baseline with event free survival

    Measured: through study completion, an average of 1 year

  15. Overall response rate based on somatic mutations

    To explore relationship of somatic mutations at baseline with the overall response rate

    Measured: through study completion, an average of 1 year

  16. Overall survival based on cytogenetic abnormalities

    To explore relationship of cytogenetic abnormalities at baseline with overall survival

    Measured: through study completion, an average of 1 year

  17. Event free survival based on cytogenetic abnormalities

    To explore relationship of cytogenetic abnormalities at baseline event free survival

    Measured: through study completion, an average of 1 year

  18. Overall response rate based on cytogenetic abnormalities

    To explore relationship of cytogenetic abnormalities at baseline with the overall response rate

    Measured: through study completion, an average of 1 year

  19. Red blood cells transfusion transfusion Independence (no use of red blood cells transfusion for a period of at least 8 weeks)

    To determine if PEVO + AZA increase the duration of red blood cells transfusion Independence (transfusion independence requires that the patient receive no red blood cells transfusions for a period of at least 8 weeks)

    Measured: through study completion, an average of 1 year

  20. Platelet transfusion Independence (no use of platelets transfusión for a period of at least 8 weeks)

    To determine if PEVO + AZA increase the duration of platelets transfusion Independence (transfusion independence requires that the patient receive no platelets transfusions for a period of at least 8 weeks)

    Measured: through study completion, an average of 1 year

  21. Biomarkers (CBF) predictive of PEVO activity

    To assess biomarkers (CBF) predictive of PEVO activity evaluated by the overall response rate and minimal residual disease

    Measured: through study completion, an average of 1 year

  22. Biomarkers (FLT3-ITD) predictive of PEVO activity

    To assess biomarkers (FLT3-ITD) predictive of PEVO activity evaluated by the overall response rate and minimal residual disease

    Measured: through study completion, an average of 1 year

  23. Biomarkers (NPM1) predictive of PEVO activity

    To assess biomarkers (NPM1) predictive of PEVO activity evaluated by the overall response rate and minimal residual disease

    Measured: through study completion, an average of 1 year

  24. Biomarkers (P53) predictive of PEVO activity

    To assess biomarkers (P53) predictive of PEVO activity evaluated by the overall response rate and minimal residual disease

    Measured: through study completion, an average of 1 year

  25. Biomarkers (IDH1/IDH2 ) predictive of PEVO activity

    To assess biomarkers (IDH1/IDH2) predictive of PEVO activity evaluated by the overall response rate and minimal residual disease

    Measured: through study completion, an average of 1 year

Timeline

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

  1. First posted16 Sep 2019
  2. Study start24 Sep 2019
  3. Primary completion30 Jun 2023
  4. Study completion30 Jul 2026 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, prospective, multicenter, open label study.
Masking
None (open label)
Enrolment
302 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04090736
Sponsor's protocol ID
PEVOLAM
Acronym
PEVOLAM
Status last verified
Jun 2026
First submitted
11 Sep 2019
Last updated
25 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28.

    PubMed 27895058

  • 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

  • Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S, Cullis CA, Doucette A, Garnsey JJ, Gaulin JL, Gershman RE, Lublinsky AR, McDonald A, Mizutani H, Narayanan U, Olhava EJ, Peluso S, Rezaei M, Sintchak MD, Talreja T, Thomas MP, Traore T, Vyskocil S, Weatherhead GS, Yu J, Zhang J, Dick LR, Claiborne CF, Rolfe M, Bolen JB, Langston SP. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009 Apr 9;458(7239):732-6. doi: 10.1038/nature07884.

    PubMed 19360080

  • Lin JJ, Milhollen MA, Smith PG, Narayanan U, Dutta A. NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer Res. 2010 Dec 15;70(24):10310-20. doi: 10.1158/0008-5472.CAN-10-2062.

    PubMed 21159650

  • Milhollen MA, Narayanan U, Soucy TA, Veiby PO, Smith PG, Amidon B. Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer Res. 2011 Apr 15;71(8):3042-51. doi: 10.1158/0008-5472.CAN-10-2122. Epub 2011 Apr 12.

    PubMed 21487042

  • Sarantopoulos J, Shapiro GI, Cohen RB, Clark JW, Kauh JS, Weiss GJ, Cleary JM, Mahalingam D, Pickard MD, Faessel HM, Berger AJ, Burke K, Mulligan G, Dezube BJ, Harvey RD. Phase I Study of the Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (TAK-924/MLN4924) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2016 Feb 15;22(4):847-57. doi: 10.1158/1078-0432.CCR-15-1338. Epub 2015 Sep 30.

    PubMed 26423795

  • Swords RT, Coutre S, Maris MB, Zeidner JF, Foran JM, Cruz J, Erba HP, Berdeja JG, Tam W, Vardhanabhuti S, Pawlikowska-Dobler I, Faessel HM, Dash AB, Sedarati F, Dezube BJ, Faller DV, Savona MR. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. Blood. 2018 Mar 29;131(13):1415-1424. doi: 10.1182/blood-2017-09-805895. Epub 2018 Jan 18.

    PubMed 29348128

  • Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. doi: 10.1182/blood-2015-01-621664. Epub 2015 May 18.

    PubMed 25987659

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pevonedistat and Azacitidine in people with Leukemia, Myeloid, Acute, run by PETHEMA Foundation at 62 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 23 inclusion and 31 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: under way, not looking for participants, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 62 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Overall survival (OS) (time frame: through study completion, an average of 1 year). 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 NCT04090736, which also lists 10 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 25 Jun 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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