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Antimetabolite

Combination Chemotherapy for Acute Myeloid Leukemia or Myelodysplastic Syndrome

Phase 1
Waitlist Available
Led By Katherine G Tarlock
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
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 1 year
Awards & highlights

Study Summary

This trial is testing a combination of pevonedistat, azacitidine, fludarabine phosphate, and cytarabine to treat patients with acute myeloid leukemia or myelodysplastic syndrome.

Who is the study for?
This trial is for patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Participants must have recovered from previous cancer treatments, meet specific blood count criteria, and not have had certain therapies within specified time frames. They should not have prior exposure to pevonedistat and must be free of uncontrolled infections or severe liver impairment.Check my eligibility
What is being tested?
The trial tests the effectiveness and side effects of a combination therapy including pevonedistat, azacitidine, fludarabine phosphate, and cytarabine in treating acute myeloid leukemia or myelodysplastic syndrome that has returned after treatment or hasn't responded to treatment.See study design
What are the potential side effects?
Potential side effects may include reactions related to the immune system's response to the drugs, organ inflammation due to drug toxicity, fatigue from chemotherapy agents, digestive issues like nausea or diarrhea, blood disorders such as anemia or clotting problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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You must wait at least 21 days after receiving any antibody treatments before participating in the trial. Also, any side effects related to previous antibody treatments should have improved and be mild.
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You are currently taking chemotherapy or other cancer drugs that can lower your blood cell count.
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If you are taking hydroxyurea to reduce the number of blood cells, you must stop taking it at least 24 hours before starting the study treatment.
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You are able to perform daily activities and take care of yourself with little to moderate help.
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You have leukemia that has not responded to at least two rounds of chemotherapy, and your bone marrow still contains a high percentage of immature cells.
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You have advanced MDS (a type of blood cancer) that has progressed to AML and have not responded well to previous treatments.
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You have to wait at least two weeks after receiving any cancer treatment before you can participate in this trial, except for hydroxyurea. You must also have fully recovered from any side effects of the previous treatment.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 1 year
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Area Under the Plasma Concentration Versus Time Curve of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
Elimination Half-life of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
Maximum Concentration of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
+4 more
Secondary outcome measures
Number of Participants With Antitumor Activity of MLN4924 (Pevonedistat)
Other outcome measures
Messenger Ribonucleic Acid (mRNA) Transcript Levels of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS

Side effects data

From 2021 Phase 2 trial • 120 Patients • NCT02610777
47%
Constipation
45%
Nausea
44%
Anaemia
40%
Fatigue
35%
Pyrexia
34%
Cough
34%
Neutropenia
27%
Diarrhoea
26%
Dyspnoea
24%
Febrile neutropenia
24%
Thrombocytopenia
21%
Decreased appetite
21%
Asthenia
21%
Vomiting
19%
Arthralgia
18%
Hypokalaemia
16%
Abdominal pain
15%
Oedema peripheral
15%
Dizziness
13%
Pneumonia
13%
Back pain
13%
Headache
13%
Pruritus
11%
Platelet count decreased
11%
Bronchitis
11%
Injection site pain
11%
Insomnia
11%
Chills
10%
Epistaxis
10%
Fall
10%
Neutrophil count decreased
10%
Oral herpes
10%
Oropharyngeal pain
10%
White blood cell count decreased
8%
Erythema
8%
Aspartate aminotransferase increased
8%
Hypomagnesaemia
8%
Muscular weakness
8%
Stomatitis
8%
Urinary tract infection
8%
Weight decreased
8%
Pleural effusion
6%
Dehydration
6%
Musculoskeletal pain
6%
Hypophosphataemia
6%
Contusion
6%
Pain in extremity
6%
Productive cough
6%
Non-cardiac chest pain Pain
6%
Sepsis
6%
Alanine aminotransferase increased
6%
Hypoalbuminaemia
6%
Hypocalcaemia
6%
Hyponatraemia
6%
Malaise
6%
Nasal congestion
6%
Non-cardiac chest pain
6%
Oral candidiasis
6%
Petechiae
6%
Nasopharyngitis
3%
Cellulitis
3%
Cerebrovascular accident
3%
Gastric haemorrhage
2%
Atrial fibrillation
2%
Congestive cardiomyopathy
2%
Acute febrile neutrophilic dermatosis
2%
Embolic stroke
2%
Endocarditis
2%
Failure to thrive
2%
Gastrointestinal necrosis
2%
Hepatic lesion
2%
Lower respiratory tract infection
2%
Lung infiltration
2%
Multiple organ dysfunction syndrome
2%
Myocardial infarction
2%
Wound infection
2%
Postoperative hypotension
2%
Acute myeloid leukaemia
2%
Ankle fracture
2%
Arthritis
2%
Arthritis reactive
2%
Autoimmune haemolytic anaemia
2%
Bacteraemia
2%
Bacterial sepsis
2%
Bronchopulmonary aspergillosis
2%
Cauda equina syndrome
2%
Cholecystitis
2%
Drug hypersensitivity
2%
Gastrointestinal ulcer perforation
2%
Haematuria
2%
Haemorrhage intracranial
2%
Hypoxia
2%
Influenza
2%
Inguinal hernia
2%
Ischaemic gastritis
2%
Leukopenia
2%
Myelodysplastic syndrome
2%
Myelodysplastic syndrome transformation
2%
Post procedural hypotension
2%
Rectal haemorrhage
2%
Renal colic
2%
Respiratory tract infection
2%
Soft tissue infection
2%
Spinal compression fracture
2%
Urinary tract infection enterococcal
2%
Urinary tract obstruction
2%
Lung infection
2%
Chronic kidney disease
2%
Death
2%
Gastritis erosive
2%
Supraventricular tachycardia
2%
Thrombophlebitis superficial
100%
80%
60%
40%
20%
0%
Study treatment Arm
Azacitidine 75 mg/m^2
Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2

Trial Design

1Treatment groups
Experimental Treatment
Group I: Treatment (cytarabine, azacitidine, pevonedistat, fludarabine)Experimental Treatment6 Interventions
Patients receive cytarabine intrathecally on day 0 at least 24 hours prior to the start of each cycle. Patients then receive azacitidine IV over 15 minutes QD on days 1-5, pevonedistat IV over 60 minutes on days 1, 3, and 5, and fludarabine phosphate IV over 30 minutes QD and cytarabine IV over 1-3 hours QD on days 6-10. Patients with CNS2 or CNS3 receive cytarabine intrathecally or methotrexate intrathecally, hydrocortisone intrathecally, and cytarabine intrathecally on days 8 and 11-34. Cycles continue for 35 days in the absence of disease progression or unacceptable toxicity. Patients with stable or greater with non-hematologic toxicities probably or definitely related to pevonedistat may receive an additional cycle of treatment.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Azacitidine
2012
Completed Phase 3
~1440
Fludarabine Phosphate
1997
Completed Phase 3
~2390
Methotrexate
2013
Completed Phase 4
~3800
Therapeutic Hydrocortisone
2012
Completed Phase 3
~340
Cytarabine
2016
Completed Phase 3
~3310
Pevonedistat
2021
Completed Phase 2
~290

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,657 Previous Clinical Trials
40,933,655 Total Patients Enrolled
Children's Oncology GroupNETWORK
453 Previous Clinical Trials
237,688 Total Patients Enrolled
Katherine G TarlockPrincipal InvestigatorCOG Phase I Consortium

Media Library

Azacitidine (Antimetabolite) Clinical Trial Eligibility Overview. Trial Name: NCT03813147 — Phase 1
Acute Myelogenous Leukemia Research Study Groups: Treatment (cytarabine, azacitidine, pevonedistat, fludarabine)
Acute Myelogenous Leukemia Clinical Trial 2023: Azacitidine Highlights & Side Effects. Trial Name: NCT03813147 — Phase 1
Azacitidine (Antimetabolite) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03813147 — Phase 1

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
Recent research and studies
clinicaltrials.govStudy
Pevonedistat, Azacitidine, Fludarabine Phosphate, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
2019. "Pevonedistat, Azacitidine, Fludarabine Phosphate, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03813147.
~2 spots leftby Apr 2025
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