Study to assess the safety and efficacy of Magrolimab versus placebo in combination with Venetoclax and Azacitidine in patients with acute myeloid leukemia (ENHANCE-3)
Zusammenfassung der Studie
This research project investigates the investigational drug Magrolimab in combination with other medications for the treatment of acute myeloid leukemia (AML). The purpose of this study is to find out whether Magrolimab in combination with Venetoclax and Azacitidine is more effective than Venetoclax and Azacitidine and equally safe in patients with newly diagnosed AML, for whom intensive chemotherapy is not an option. Study participants will be assigned to either the group receiving Magrolimab in combination with Venetoclax and Azacitidine or the control group receiving a placebo (an infusion without active ingredients that looks like Magrolimab) along with Venetoclax and Azacitidine. There is a 50% chance of receiving Magrolimab and a 50% chance of receiving a placebo. Participation in the study will last approximately 9 months or longer. The pre-screening date is excluded. Active participation in the study, including treatment with the investigational drug, may continue as long as participants tolerate the study treatment, the cancer does not progress, no new AML treatment is started, and the study is not discontinued. The study treatment (Venetoclax and Azacitidine) will be administered in 28-day (4-week) cycles, with Magrolimab or placebo administered in parallel. Participants will need to come to the clinic more frequently for visit appointments at specific times during the study. There may be no benefit from participating in this study. In previous studies of Magrolimab, the most common drug-related side effects in more than one in ten people who received at least one dose of Magrolimab were the following: anemia (low red blood cell count), chills, decreased appetite, diarrhea, fatigue, fever, headache, infusion-related reactions, nausea, and vomiting.
(BASEC)
Untersuchte Intervention
This is a double-blind, placebo-controlled study in which participants are assigned to one of two groups:
• Magrolimab, Venetoclax, and Azacitidine
• Placebo, Venetoclax, and Azacitidine
Double-blind means that neither participants nor the investigator will know which study treatment is being administered.
Placebo-controlled means that a dummy drug may be administered as an infusion that contains no active ingredients but looks like Magrolimab.
Randomized means that study treatment is chosen randomly – like flipping a coin. There is a 50% chance that participants will receive Magrolimab and a 50% chance of receiving a placebo.
(BASEC)
Untersuchte Krankheit(en)
Acute myeloid leukemia (AML) in patients for whom chemotherapy is not an option.
(BASEC)
Previously untreated patients with histologically confirmed acute myeloid leukemia (AML) according to World Health Organization (WHO) criteria, who are not eligible for treatment with standard chemotherapy due to their age or disease. (BASEC)
Ausschlusskriterien
- Previous treatment with substances defined in the protocol - Clinical suspicion of or documented active involvement of the central nervous system (CNS) in AML - Individuals with acute promyelocytic leukemia - Second malignant disease Note: Additional inclusion/exclusion criteria defined in the protocol apply. (BASEC)
Studienstandort
Bern
(BASEC)
Sponsor
nicht verfügbar
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Prof. Dr. med. Thomas Pabst
+41 (0) 31 632 41 14
thomas.pabst@clutterinsel.ch(BASEC)
Allgemeine Auskünfte
Gilead Sciences
(ICTRP)
Wissenschaftliche Auskünfte
Gilead Sciences
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
21.02.2023
(BASEC)
ICTRP Studien-ID
NCT05079230 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
nicht verfügbar
Wissenschaftlicher Titel
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Newly Diagnosed, Previously Untreated Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy (ICTRP)
Öffentlicher Titel
Study of Magrolimab Versus Placebo in Combination With Venetoclax and Azacitidine in Participants With Acute Myeloid Leukemia (ICTRP)
Untersuchte Krankheit(en)
Acute Myeloid Leukemia (ICTRP)
Untersuchte Intervention
Drug: MagrolimabDrug: VenetoclaxDrug: AzacitidineDrug: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)
Ein-/Ausschlusskriterien
Key Inclusion Criteria:
- Previously untreated individuals with histological confirmation of acute myeloid
leukemia (AML) by World Health Organization (WHO) criteria who are ineligible for
treatment with a standard cytarabine and anthracycline induction regimen due to age,
or comorbidity. Individuals must be considered ineligible for intensive
chemotherapy, defined by the following:
- = 75 years of age Or
- = 18 to 74 years of age with at least 1 of the following comorbidities:
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
- Diffusing capacity of the lung of carbon monoxide = 65% or forced
expiratory volume in 1 second = 65%
- Left ventricular ejection fraction = 50%
- Baseline creatinine clearance = 30 mL/min to < 45 mL/min calculated by the
Cockcroft Gault formula or measured by 24-hour urine collection
- Hepatic disorder with total bilirubin > 1.5 x upper limit of normal (ULN)
- Any other comorbidity that the investigator judges to be incompatible with
intensive chemotherapy
- ECOG performance status:
- Of 0 to 2 for individuals = 75 years of age Or
- Of 0 to 3 for individuals = 18 to 74 years of age
- Individuals with white blood cell (WBC) count = 20 x 10^3/L prior to randomization.
If the individual's WBC is > 20 x10^3/L prior to randomization, the individual can
be enrolled, assuming all other eligibility criteria are met. However, the WBC
should be = 20 x 10^3/L prior to the first dose of study treatment and prior to
each magrolimab/placebo dose during Cycle 1.
- Note: Individuals can be treated with hydroxyurea and/or leukapheresis prior to
randomization and throughout the study to reduce the WBC to = 20 x 10^3/L to
enable eligibility for study drug dosing
- Hemoglobin must be = 9 g/dL prior to initial dose of study treatment
- Note: Transfusions are allowed to meet hemoglobin eligibility
- Pretreatment blood cross-match completed
Key Exclusion Criteria:
- Prior treatment with any of the following:
- cluster of differentiation 47 (CD47) or signal regulatory protein alpha
(SIRPa)-targeting agents
- Antileukemic therapy for the treatment of AML (eg, hypomethylating agents
(HMAs), low-dose cytarabine, and/or venetoclax), excluding hydroxyurea
- Note: Individuals with prior MDS who have not received prior HMAs or
venetoclax or chemotherapeutic agents for MDS may be enrolled in the
study. Prior treatment with myelodysplastic syndrome (MDS) therapies
including, but not limited to lenalidomide, erythroid-stimulating agents,
or similar red blood cell negative (RBC-), white blood cell negative
(WBC-), or platelet-direct therapies or growth factors is allowed for
these individuals.
- Clinical suspicion of or documented active central nervous system (CNS) involvement
with AML
- Individuals who have acute promyelocytic leukemia
- Second malignancy, except MDS, treated basal cell or localized squamous skin
carcinomas, localized prostate cancer, or other malignancies for which individuals
are not on active anticancer therapies and have had no evidence of active malignancy
for at least 1 year
Note: Other protocol defined Inclusion/Exclusion criteria may apply. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Overall Survival (OS) (ICTRP)
Rate of Complete Remission (CR) + Complete Remission With Partial Hematologic Recovery (CRh);Rate of Complete Remission (CR);Event-Free Survival (EFS);Duration of CR + CRh in Participants Who Achieved Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh);Duration of Complete Remission (DCR) in Participants Who Achieved Complete Remission (CR);Rate of CR/CRh Without Minimal Residual Disease (CR/CRhMRD-);Rate of CR Without Minimal Residual Disease (CRMRD-);Red Blood Cell (RBC) Transfusion Independence Conversion Rate;Platelet Transfusion Independence Conversion Rate;Time to First Deterioration (TTD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Scale;Time to First Deterioration (TTD) on the EORTC QLQ-C30 Physical Functioning Scale;Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs);Percentage of Participants Experiencing Grade 3 or Higher Treatment-Emergent Laboratory Abnormalities;Serum Concentration of Magrolimab Over Time;Percentage of Participants With Anti-Magrolimab Antibodies;Maximum Levels of Serum Anti-Magrolimab Antibodies (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Gilead Study Director, Gilead Sciences (ICTRP)
Sekundäre IDs
2021-003434-36, MOH_2022-08-15_011983, GS-US-590-6154 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT05079230 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar