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Anti-metabolites

Azacitidine + Nivolumab/Midostaurin vs. Decitabine/Cytarabine for Acute Myeloid Leukemia

Phase 2 & 3
Waitlist Available
Led By Laura C Michaelis
Research Sponsored by National Cancer Institute (NCI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Patients must be able to swallow oral medications without crushing or chewing
Patients must have morphologically confirmed, previously untreated acute myeloid leukemia (AML) or MDS with excess blasts-2 (MDS-EB-2)
Timeline
Screening 3 weeks
Treatment Varies
Follow Up duration of treatment and follow up until death or 5 years post randomization (registration to step 2).
Awards & highlights
No Placebo-Only Group

Summary

This trial is studying azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone to see how well they work compared to each other in treating patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome.

Who is the study for?
This trial is for older adults with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Participants must not need concurrent cancer therapy (except hormonal), have acceptable liver function, be able to swallow pills, and consent to specimen banking. Women of childbearing age and sexually active men must use effective contraception. Those with central nervous system leukemia, prior specific treatments like midostaurin or DNA-methyltransferase inhibitors, or who are pregnant/nursing are excluded.
What is being tested?
The study compares the effectiveness of azacitidine alone versus in combination with nivolumab (an immunotherapy) or midostaurin (a growth blocker), against decitabine and cytarabine alone in treating certain blood cancers. It aims to determine which treatment stops cancer cells from growing by either killing them directly or boosting the immune response against them.
What are the potential side effects?
Potential side effects include reactions related to chemotherapy such as nausea, fatigue, low blood counts leading to increased infection risk; immunotherapy may cause autoimmune-like conditions where the body attacks its own cells; midostaurin can lead to gastrointestinal symptoms and potential heart rhythm abnormalities.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I can swallow pills without needing to crush or chew them.
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I have been diagnosed with AML or MDS-EB-2 and have not received treatment.
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My cancer is in my blood or bone marrow, not just in other body parts.
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I am eligible for at least one of the treatment options S1612B or S1612C.
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I am suspected to have AML or MDS-EB-2 without prior treatment.
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I do not have an ongoing infection that isn't getting better with treatment.
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I haven't needed treatment for an autoimmune disease in the last 2 years.
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I have not had treatments with midostaurin, anti-PD-1/L1, DNA-methyltransferase inhibitors, or intensive therapy for MDS.
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I do not have APL, biphenotypic leukemia, or blastic transformation of CML.
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I do not have acute myeloid leukemia in my brain or spinal cord.
Select...
I do not have leukemia in my brain or spinal cord.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~duration of treatment and follow up until death or 5 years post randomization (registration to step 2).
This trial's timeline: 3 weeks for screening, Varies for treatment, and duration of treatment and follow up until death or 5 years post randomization (registration to step 2). for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
OS (Phase III)
Overall Survival (OS) (Phase II)
Secondary study objectives
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Other study objectives
Cumulative Incidence of Relapse Defined as Achieving CR or CRi
Cytogenetic Abnormalities, Risk Categories, and Mutations in Bone Marrow
Event-free Survival (EFS)
+5 more

Side effects data

From 2007 Phase 3 trial • 358 Patients • NCT00071799
67%
Thrombocytopenia
65%
Neutropenia
50%
Constipation
48%
Nausea
48%
Anaemia
43%
Injection site erythema
29%
Injection site reaction
27%
Vomiting
26%
Pyrexia
24%
Fatigue
22%
Diarrhoea
19%
Nasopharyngitis
19%
Cough
18%
Injection site pain
18%
Leukopenia
17%
Acute myeloid leukaemia
15%
Asthenia
15%
Dyspnoea
15%
Epistaxis
14%
Headache
14%
Anorexia
13%
Oedema peripheral
12%
Abdominal pain
12%
Haematoma
11%
Febrile neutropenia
11%
Pneumonia
11%
Transfusion reaction
11%
Petechiae
11%
Pruritus
10%
Oral herpes
10%
Dizziness
10%
Rash
9%
Arthralgia
9%
Back pain
9%
Bronchitis
9%
Insomnia
9%
Upper respiratory tract infection
9%
Hypertension
8%
Weight decreased
8%
Contusion
7%
Haemorrhoids
7%
Erythema
7%
Urinary tract infection
7%
Lethargy
6%
Abdominal pain upper
6%
Muscle spasms
6%
Gingival bleeding
6%
Injection site rash
6%
Influenza
6%
Oral candidiasis
6%
Rhinitis
6%
Pain in extremity
6%
Hypotension
6%
Dyspepsia
6%
Injection site haematoma
6%
Hypokalaemia
6%
Haematuria
6%
Pharyngolaryngeal pain
5%
Chest pain
5%
Mouth ulceration
5%
Musculoskeletal pain
5%
Depression
5%
Oedema
5%
Pharyngitis
5%
Anxiety
5%
Ecchymosis
5%
Injection site bruising
5%
Injection site induration
5%
Dyspnoea exertional
4%
Pain
4%
Bone pain
4%
Alopecia
4%
Skin lesion
3%
Conjunctival haemorrhage
3%
Respiratory tract infection
3%
Tachycardia
3%
Productive cough
3%
Stomatitis
3%
Dry mouth
3%
Gingivitis
3%
Chills
3%
Sinusitis
3%
Sepsis
3%
Fall
3%
Alanine aminotransferase increased
3%
Sleep disorder
2%
Gastritis
2%
Neutropenic sepsis
2%
Purpura
2%
Catheter site haematoma
2%
Muscular weakness
2%
Nasal congestion
2%
Hyperuricaemia
2%
Cardiac failure
2%
Bronchopneumonia
2%
Lymphopenia
2%
Gastrooesophageal reflux disease
2%
Rectal haemorrhage
2%
General physical health deterioration
2%
Pallor
2%
Septic shock
2%
Myelodysplastic syndrome
2%
Cerebral haemorrhage
2%
Pitting oedema
2%
Procedural pain
2%
Syncope
1%
Mouth haemorrhage
1%
Psychotic disorder
1%
Gastrointestinal pain
1%
Perianal abscess
1%
Haemorrhoidal haemorrhage
1%
Ventricular tachycardia
1%
Anal haemorrhage
1%
Lung infection
1%
Subileus
1%
Myocardial infarction
1%
Oral soft tissue disorder
1%
Catheter site haemorrhage
1%
Hypophosphataemia
1%
Renal colic
1%
Strabismus
1%
Cellulitis
1%
Eye Haemorrhage
1%
Peripheral vascular disorder
1%
Enterobacter infection
1%
Gastrointestinal haemorrhage
1%
Tooth abscess
1%
Food poisoning
1%
Intestinal haemorrhage
1%
Corynebacterium infection
1%
Clostridium difficile colitis
1%
Delirium
1%
Musculoskeletal chest pain
1%
Pancytopenia
1%
Endophthalmitis
1%
Haematemesis
1%
Tooth disorder
1%
Meningitis
1%
Subcutaneous abscess
1%
Confusional state
1%
Benign prostatic hyperplasia
1%
Hypoxia
1%
Abdominal discomfort
1%
Atrial fibrillation
1%
Angle closure glaucoma
1%
Conjunctivitis
1%
Fungal skin infection
1%
Angina pectoris
1%
Herpes zoster
1%
Salmonella sepsis
1%
Subdiaphragmatic abscess
1%
Blood lactate dehydrogenase increased
1%
Ocular hyperaemia
1%
Catheter site pain
1%
Joint swelling
1%
Transient ischaemic attack
1%
Pulmonary embolism
1%
Pleural effusion
1%
Cardiac failure acute
1%
Vertigo
1%
Oesophageal carcinoma
1%
Myopia
1%
Retinal artery occlusion
1%
Squamous cell carcinoma of skin
1%
Haemoptysis
1%
Lung infiltration
1%
Respiratory failure
1%
Pulmonary oedema
1%
Pulmonary fibrosis
1%
Hallucination
1%
Colitis ulcerative
1%
Injection site nodule
1%
Bacteraemia
1%
Bile duct stone
1%
Hepatic function abnormal
1%
Fungal sepsis
1%
Gasteroenteritis
1%
Gasteroenteritis salmonella
1%
Laryngopharyngitis
1%
Lobar pneumonia
1%
Lower respiratory tract infection
1%
Pulmonary tuberculosis
1%
Sialoadenitis
1%
Splenic abscess
1%
Staphylococcal bacteraemia
1%
Clavicle fracture
1%
Hip fracture
1%
Traumatic intracranial haemorrhage
1%
Diabetes mellitus
1%
Colon cancer
1%
Lung adenocarcinoma
1%
Neoplasm prostate
1%
Urinary tract neoplasm
1%
Coma
1%
Haemorrhage intracranial
1%
Renal failure
1%
Urethral stenosis
1%
Acute pulmonary oedema
1%
Acute respiratory failure
1%
Hypoalbuminaemia
1%
Hyponatraemia
1%
Lymphadenopathy
1%
Gingival pain
1%
Generalised oedema
1%
Catheter related infection
1%
Neck pain
1%
Dermatitis allergic
1%
Rash macular
1%
Urticaria
1%
Bone marrow failure
1%
Pericardial effusion
1%
Hypothyroidism
1%
Retinal Haemorrhage
1%
Retinal tear
1%
Abdominal wall abscess
1%
Abscess neck
1%
Ear infection
1%
Enterobacter bacteraemia
1%
Mucormycosis
1%
Neutropenic infection
1%
Parotitis
1%
Pneumonia fungal
1%
Synovial rupture
1%
Osteoporosis
1%
Myelofibrosis
1%
Loss of consciousness
1%
Urinary retention
1%
Pneumonitis
1%
Actinic keratosis
1%
Aortic aneurysm
1%
Circulatory collapse
1%
Bronchopulmonary aspergillosis
1%
Bradycardia
1%
Aphthous stomatitis
1%
Mucosal inflammation
1%
Staphylococcal infection
1%
Viral upper respiratory tract infection
1%
Scratch
1%
Thermal burn
1%
Aspartate aminotransferase increased
1%
Hypocalcaemia
1%
Bursitis
1%
Sinus headache
1%
Chromaturia
1%
Proteinuria
1%
Pleurisy
1%
Rash papular
1%
Rash pruritic
100%
80%
60%
40%
20%
0%
Study treatment Arm
Azacitidine
Low-dose Cytarabine
Best Supportive Care Only
Standard Chemotherapy

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups
Experimental Treatment
Active Control
Group I: Arm D (decitabine, cytarabine)Experimental Treatment3 Interventions
INDUCTION: Patients receive decitabine IV over 2 hours on days 1-5 and cytarabine IV continuously on days 6-11. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients deemed stable at the discretion of the treating physician receive decitabine as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II: Arm C (azacitidine, midostaurin)Experimental Treatment3 Interventions
Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group III: Arm B (azacitidine, nivolumab)Experimental Treatment3 Interventions
Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group IV: Arm A (azacitidine)Active Control2 Interventions
Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Midostaurin
2018
Completed Phase 3
~1640
Decitabine
2004
Completed Phase 3
~1680
Nivolumab
2015
Completed Phase 3
~4010
Azacitidine
2012
Completed Phase 3
~1440
Cytarabine
2016
Completed Phase 3
~3330

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,924 Previous Clinical Trials
41,017,875 Total Patients Enrolled
Laura C MichaelisPrincipal InvestigatorSWOG Cancer Research Network
~10 spots leftby Nov 2025
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