Study to Compare Azacitidine Plus Pevonedistat Versus Azacitidine in Patients With Acute Myeloid Leukemia Not Eligible for Standard Chemotherapy
NCT ID: NCT04090736
Last Updated: 2025-03-17
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
ACTIVE_NOT_RECRUITING
Clinical Phase
PHASE3
Total Enrollment
302 participants
Study Classification
INTERVENTIONAL
Study Start Date
2019-09-24
Study Completion Date
2025-06-30
Brief Summary
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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.
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Detailed Description
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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
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
Conditions
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Leukemia, Myeloid, Acute
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Randomized, prospective, multicenter, open label study.
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Arm A: Pevonedistat plus Azacitidine
Pevonedistat 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)
Group Type
EXPERIMENTAL
Pevonedistat
Intervention Type
DRUG
Pevonedistat 20 mg/m2 intravenous on days 1, 3, and 5 (28-day cycles)
Azacitidine
Intervention Type
DRUG
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
Arm B: Azacitidine
Azacitidine 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)
Group Type
ACTIVE_COMPARATOR
Azacitidine
Intervention Type
DRUG
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
Interventions
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Pevonedistat
Pevonedistat 20 mg/m2 intravenous on days 1, 3, and 5 (28-day cycles)
Intervention Type
DRUG
Azacitidine
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
Intervention Type
DRUG
Eligibility Criteria
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Inclusion Criteria
1. Male or female patients 18 years or older
2. Morphological diagnosis of Acute Myeloid Leukemia (AML) (WHO criteria 2008)
3. 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).
4. Newly diagnosed AML
5. 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:
1. ≥ 75 years of age
2. 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).
6. 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.
7. 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.
8. 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.
9. 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.)
10. 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.
* The reason a patient is not eligible for intensive chemotherapy must be documented in the electronic case report form (eCRF).
5. Patients with either clinical evidence of or history of central nervous system involvement by AML.
6. 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.
7. 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.
8. Subject has a white blood cell count \> 50 × 109/L.
9. Contraindications for PEVO or AZA.
10. Known hypersensitivity to pevonedistat or its excipients.
11. 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).
12. 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.
13. 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).
14. 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
15. 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).
16. Known hepatic cirrhosis or severe preexisting hepatic impairment.
17. 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.
18. 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.
19. Treatment with strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers (see Appendix 8) within 14 days before the first dose of pevonedistat.
20. Patients with uncontrolled coagulopathy or bleeding disorder.
21. High blood pressure which cannot be controlled by standard treatments
22. Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to institutional guidelines.
23. 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.
24. 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.
25. Systemic antineoplastic therapy for malignant conditions other than myeloid neoplasms within 14 days before the first dose of any study drug.
2. Morphological diagnosis of Acute Myeloid Leukemia (AML) (WHO criteria 2008)
3. 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).
4. Newly diagnosed AML
5. 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:
1. ≥ 75 years of age
2. 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).
6. 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.
7. 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.
8. 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.
9. 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.)
10. 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.
* The reason a patient is not eligible for intensive chemotherapy must be documented in the electronic case report form (eCRF).
5. Patients with either clinical evidence of or history of central nervous system involvement by AML.
6. 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.
7. 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.
8. Subject has a white blood cell count \> 50 × 109/L.
9. Contraindications for PEVO or AZA.
10. Known hypersensitivity to pevonedistat or its excipients.
11. 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).
12. 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.
13. 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).
14. 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
15. 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).
16. Known hepatic cirrhosis or severe preexisting hepatic impairment.
17. 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.
18. 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.
19. Treatment with strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers (see Appendix 8) within 14 days before the first dose of pevonedistat.
20. Patients with uncontrolled coagulopathy or bleeding disorder.
21. High blood pressure which cannot be controlled by standard treatments
22. Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to institutional guidelines.
23. 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.
24. 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.
25. Systemic antineoplastic therapy for malignant conditions other than myeloid neoplasms within 14 days before the first dose of any study drug.
Exclusion Criteria
1. 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.
2. Subject has history MPN with BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
3. Genetic diagnosis of acute promyelocytic leukemia.
4. Eligible for intensive chemotherapy and/or allogeneic stem cell transplantation.
2. Subject has history MPN with BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
3. Genetic diagnosis of acute promyelocytic leukemia.
4. Eligible for intensive chemotherapy and/or allogeneic stem cell transplantation.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Millennium Pharmaceuticals, Inc.
INDUSTRY
Sponsor Role
collaborator
Dynamic Science S.L.
INDUSTRY
Sponsor Role
collaborator
PETHEMA Foundation
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Locations
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Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, A Coruña, Spain
Site Status
Hospital Txagorritxu
Vitoria-Gasteiz, Alava, Spain
Site Status
ICO Badalona- Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
Site Status
ICO Hospitalet- Hospital Duran i Reynals
Hospitalet Del Llobregat, Barcelona, Spain
Site Status
Hospital Universitario Donostia
San Sebastián, Guipuzcoa, Spain
Site Status
Complejo Hospitalario de Jaén
Jaén, Jaen, Spain
Site Status
Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín
Las Palmas de Gran Canaria, Las Palmas, Spain
Site Status
Hospital Universitario Quirón Madrid
Pozuelo de Alarcón, Madrid, Spain
Site Status
Hospital Universitario Infanta Sofía
San Sebastián de los Reyes, Madrid, Spain
Site Status
Hospital Regional Universitario de Málaga
Málaga, Malaga, Spain
Site Status
Hospital Universitario Virgen de la Victoria
Málaga, Malaga, Spain
Site Status
Hospital General Universitario Santa Lucía
Cartagena, Murcia, Spain
Site Status
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, Spain
Site Status
Hospital Universitario de Canarias
San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain
Site Status
Hospital Universitario Virgen del Rocío
Seville, Sevila, Spain
Site Status
Hospital General Nuestra Señora del Prado
Talavera de la Reina, Toledo, Spain
Site Status
Hospital Universitario de Cruces
Barakaldo, Vizcaya, Spain
Site Status
Hospital Universitario de Basurto
Bilbao, Vizcaya, Spain
Site Status
Hospital Universitario de Galdakao
Galdakao, Vizcaya, Spain
Site Status
Complejo Hospitalario Universitario A Coruña
A Coruña, , Spain
Site Status
Complejo Hospitalario Universitario de Albacete
Albacete, , Spain
Site Status
Hospital General Universitario de Alicante
Alicante, , Spain
Site Status
Complejo Hospitalario Torrecárdenas
Almería, , Spain
Site Status
Hospital Dr. José Molina Orosa
Arrecife, , Spain
Site Status
Hospital San Agustin
Avilés, , Spain
Site Status
Complejo Asistencial de Ávila
Ávila, , Spain
Site Status
Hospital Universitario de Badajoz
Badajoz, , Spain
Site Status
Hospital del Mar
Barcelona, , Spain
Site Status
Hospital Vithas Xanit Internacional
Benalmádena, , Spain
Site Status
Hospital Universitario de Burgos
Burgos, , Spain
Site Status
Hospital Universitario Puerta del Mar
Cadiz, , Spain
Site Status
Hospital General Universitario de Castellón
Castelló, , Spain
Site Status
Complejo Hospitalario de Cáceres
Cáceres, , Spain
Site Status
Complejo Hospitalario Regional Reina Sofía
Córdoba, , Spain
Site Status
Hospital General Universitario de Elche
Elche, , Spain
Site Status
ICO Girona- Hospital Universitari Dr Josep Trueta
Girona, , Spain
Site Status
Hospital Universitario de Guadalajara
Guadalajara, , Spain
Site Status
Hospital Universitario Juan Ramón Jiménez
Huelva, , Spain
Site Status
Hospital San Jorge
Huesca, , Spain
Site Status
Complejo Hospitalario Lucus Augusti
Lugo, , Spain
Site Status
Hospital Universitario Ramón y Cajal
Madrid, , Spain
Site Status
Hospital Clínico San Carlos
Madrid, , Spain
Site Status
Hospital Universitario Fundación Jiménez Díaz
Madrid, , Spain
Site Status
Hospital Universitario 12 de Octubre
Madrid, , Spain
Site Status
Hospital Universitario Madrid Norte Sanchinarro
Madrid, , Spain
Site Status
Hospital Quirón de Málaga
Málaga, , Spain
Site Status
Hospital General Universitario Morales Meseguer
Murcia, , Spain
Site Status
Complexo Hospitalario Universitario de Ourense
Ourense, , Spain
Site Status
Hospital Son Llàtzer
Palma de Mallorca, , Spain
Site Status
Complexo Hospitalario de Pontevedra
Pontevedra, , Spain
Site Status
Hospital Universitario de Salamanca
Salamanca, , Spain
Site Status
Complejo Hospitalario Universitario Nuestra Señora de la Candelaria
Santa Cruz de Tenerife, , Spain
Site Status
Hospital General de Segovia
Segovia, , Spain
Site Status
Hospital de Valme
Seville, , Spain
Site Status
Hospital Universitari Joan XXIII
Tarragona, , Spain
Site Status
Hospital Virgen de la Salud
Toledo, , Spain
Site Status
Hospital Clínico Universitario de Valencia
Valencia, , Spain
Site Status
Hospital Universitario Dr. Peset Aleixandre
Valencia, , Spain
Site Status
Hospital Universitari i Politecnic La Fe
Valencia, , Spain
Site Status
Hospital Clínico Universitario de Valladolid
Valladolid, , Spain
Site Status
Hospital Clínico Universitario Lozano Blesa
Zaragoza, , Spain
Site Status
Hospital Universitario Miguel Servet
Zaragoza, , Spain
Site Status
Countries
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Spain
References
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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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
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.
Reference Type
RESULT
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.
Reference Type
RESULT
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.
Reference Type
RESULT
Shah JJ, Jakubowiak AJ, O'Connor OA, Orlowski RZ, Harvey RD, Smith MR, Lebovic D, Diefenbach C, Kelly K, Hua Z, Berger AJ, Mulligan G, Faessel HM, Tirrell S, Dezube BJ, Lonial S. Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma. Clin Cancer Res. 2016 Jan 1;22(1):34-43. doi: 10.1158/1078-0432.CCR-15-1237. Epub 2015 Nov 11.
Reference Type
RESULT
Bhatia S, Pavlick AC, Boasberg P, Thompson JA, Mulligan G, Pickard MD, Faessel H, Dezube BJ, Hamid O. A phase I study of the investigational NEDD8-activating enzyme inhibitor pevonedistat (TAK-924/MLN4924) in patients with metastatic melanoma. Invest New Drugs. 2016 Aug;34(4):439-49. doi: 10.1007/s10637-016-0348-5. Epub 2016 Apr 8.
Reference Type
RESULT
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PEVOLAM
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Identifier Source: org_study_id
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