Study Summary
This trial is testing nivolumab, azacitidine, and ipilimumab to treat patients with AML that has not responded to previous treatment or has returned after a period of improvement.
Eligible Conditions
- Myelodysplastic Syndrome
- Secondary Acute Myeloid Leukemia
- Therapy-Related Acute Myeloid Leukemia
- Acute Biphenotypic Leukemia
- Chronic Myelomonocytic Leukemia
- Acute Recurrent Myeloid Leukemia
- Acute Myeloid Leukemia (AML) arising from Myelodysplastic Syndrome (MDS)
- Refractory Acute Myelogenous Leukemia
Treatment Effectiveness
Phase-Based Effectiveness
Phase 2
Study Objectives
3 Primary · 3 Secondary · Reporting Duration: Up to 5 years
Year 5
Immunological changes in peripheral blood and bone marrow
Bone Marrow
Up to 28 days
Maximum tolerated dose of nivolumab with dihydro-5-azacytidine, based on the incidence of dose limiting toxicity assessed by the Common Terminology Criteria for Adverse Events (CTCAE) (Lead-in phase)
Up to 5 years
Disease-free survival
Induction of hypomethylation and deoxyribonucleic acid damage during therapy
Overall survival
Progression-free survival
Month 3
Efficacy as measured by the overall response rate defined as complete response + complete response with incomplete platelet recovery + complete response with incomplete count recovery + partial response + marrow clearance of blasts (Phase II)
Incidence of adverse events graded according to CTCAE
Trial Safety
Phase-Based Safety
This is further along than 68% of similar trials
Side Effects for
Investigator Choice of Chemotherapy
57%Nausea
54%Anaemia
51%Fatigue
39%Decreased appetite
36%Malignant neoplasm progression
32%Constipation
31%Diarrhoea
30%Cough
29%Vomiting
29%Dyspnoea
25%Oedema peripheral
24%Back pain
21%Neutropenia
21%Pyrexia
19%Hypomagnesaemia
19%Headache
18%Arthralgia
16%Asthenia
16%Dizziness
16%Neutrophil count decreased
15%Thrombocytopenia
15%Insomnia
14%Weight decreased
14%Hyponatraemia
14%Rash
14%Platelet count decreased
13%Blood creatinine increased
13%White blood cell count decreased
12%Pain in extremity
12%Pruritus
12%Hypokalaemia
12%Abdominal pain
11%Alanine aminotransferase increased
11%Aspartate aminotransferase increased
11%Myalgia
10%Pneumonia
10%Muscular weakness
10%Productive cough
10%Alopecia
10%Dry skin
10%Chest pain
10%Hypoalbuminaemia
10%Dysgeusia
9%Abdominal pain upper
9%Mucosal inflammation
9%Hypothyroidism
9%Upper respiratory tract infection
9%Peripheral sensory neuropathy
8%Lacrimation increased
8%Non-cardiac chest pain
8%Nasopharyngitis
8%Dysphonia
8%Epistaxis
8%Haemoptysis
8%Stomatitis
7%Anxiety
7%Bronchitis
7%Hypertension
7%Hyperkalaemia
7%Dehydration
7%Chills
7%Blood alkaline phosphatase increased
7%Hyperglycaemia
7%Lymphocyte count decreased
6%Oropharyngeal pain
6%Pneumonitis
6%Pleural effusion
6%Neuropathy peripheral
6%Hypophosphataemia
6%Leukopenia
5%Hypotension
5%Dry mouth
5%Muscle spasms
5%Pain
5%Urinary tract infection
5%Gamma-glutamyltransferase increased
5%Malaise
5%Depression
5%Rash maculo-papular
5%Dyspepsia
5%Musculoskeletal chest pain
4%Fall
4%Pulmonary embolism
3%Myocardial infarction
3%Metastases to central nervous system
3%Musculoskeletal pain
3%Chronic obstructive pulmonary disease
3%Febrile neutropenia
2%Adrenal insufficiency
2%Atrial fibrillation
2%Sepsis
2%Malignant pleural effusion
2%Embolism
2%Cardiac failure
2%General physical health deterioration
1%Pancytopenia
1%Lung cancer metastatic
1%Small intestinal haemorrhage
1%Neoplasm progression
1%Gastrointestinal haemorrhage
1%Colitis
1%Appendicitis
1%Respiratory tract infection
1%Bone pain
1%Ataxia
1%Syncope
1%Bronchial obstruction
1%Pneumothorax
1%Circulatory collapse
1%Superior vena cava syndrome
1%Respiratory failure
1%Seizure
1%Atrial flutter
1%Pericardial effusion
1%Ileus
1%Small intestinal obstruction
1%Performance status decreased
1%Skin infection
1%Femur fracture
1%Hypercalcaemia
1%Cancer pain
1%Pericardial effusion malignant
1%Confusional state
1%Tumour pain
Awards & Highlights
No Placebo Group
All patients enrolled in this trial will receive the new treatment.
All Individual Drugs Already Approved
Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.
Approved for 5 Other Conditions
This treatment demonstrated efficacy for 5 other conditions.
Trial Design
2 Treatment Groups
Arm I (azacitidine, nivolumab)
1 of 2
Arm II (azacitidine, nivolumab, ipilimumab)
1 of 2
Experimental Treatment
182 Total Participants · 2 Treatment Groups
Primary Treatment: Nivolumab · No Placebo Group · Phase 2
Arm I (azacitidine, nivolumab)Experimental Group · 3 Interventions: Azacitidine, Nivolumab, Laboratory Biomarker Analysis · Intervention Types: Drug, Biological, Other
Arm II (azacitidine, nivolumab, ipilimumab)Experimental Group · 4 Interventions: Ipilimumab, Azacitidine, Nivolumab, Laboratory Biomarker Analysis · Intervention Types: Biological, Drug, Biological, Other
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Ipilimumab
FDA approved
Azacitidine
FDA approved
Nivolumab
FDA approved
Trial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: up to 5 years
Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
2,849 Previous Clinical Trials
1,793,343 Total Patients Enrolled
National Cancer Institute (NCI)NIH
13,279 Previous Clinical Trials
41,234,676 Total Patients Enrolled
Naval DaverPrincipal InvestigatorM.D. Anderson Cancer Center
3 Previous Clinical Trials
180 Total Patients Enrolled
Eligibility Criteria
Age 18+ · All Participants · 5 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:You are allowed to have received certain types of prior treatments such as hydroxyurea, chemotherapy, biological or targeted therapy.
You have acute myeloid leukemia (AML) and have tried one prior treatment that did not work. If you are in remission after a stem cell transplant or have only used hydroxyurea, it will not count as a prior treatment.
You are over 65 years old and have never been treated for acute myeloid leukemia (AML). If you have been treated before, it was not with chemotherapy for AML. You may have received other medications for this condition.
If you have a specific type of blood cancer called myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) that has progressed to acute myeloid leukemia (AML), you may still be eligible for the study. Your previous treatment for MDS or CMML will not be considered as prior treatment for AML, so you will be considered for the frontline elderly group. The diagnosis will be made using the World Health Organization (WHO) classification.
You have a condition called graft versus host disease (GVHD), but it's not too severe and you have been taking medicine to suppress your immune system for at least two weeks. You may also be using corticosteroids.
References
- El Hussein S, Daver N, Liu JL, Kornblau S, Fang H, Konoplev S, Kantarjian H, Khoury JD. Microsatellite Instability Assessment by Immunohistochemistry in Acute Myeloid Leukemia: A Reappraisal and Review of the Literature. Clin Lymphoma Myeloma Leuk. 2022 Jun;22(6):e386-e391. doi: 10.1016/j.clml.2021.12.004. Epub 2021 Dec 9. Review.
- El Hussein S, Daver N, Liu JL, Kornblau S, Fang H, Konoplev S, Kantarjian H, Khoury JD. Microsatellite Instability Assessment by Immunohistochemistry in Acute Myeloid Leukemia: A Reappraisal and Review of the Literature. Clin Lymphoma Myeloma Leuk. 2022 Jun;22(6):e386-e391. doi: 10.1016/j.clml.2021.12.004. Epub 2021 Dec 9.
- 2015. "Nivolumab and Azacitidine With or Without Ipilimumab in Treating Patients With Refractory/Relapsed or Newly Diagnosed Acute Myeloid Leukemia". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02397720.