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DNA Methyltransferase Inhibitor

Pevonedistat + Azacitidine for Advanced Leukemias (PANTHER Trial)

Phase 3

Waitlist Available

Research Sponsored by Millennium Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has MDS or CMML with one of the following Prognostic Risk Categories based on the Revised International Prognostic Scoring System (IPSS-R): Very high (>6 points), High (>4.5-6 points), Intermediate (>3-4.5 points) with >=5% bone marrow myeloblasts

Has Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to year 1

Awards & highlights

PANTHER Trial Summary

This trial is testing whether adding pevonedistat to azacitidine helps people with MDS, CMML, or low-blast AML live longer without disease progression or death.

Who is the study for?

This trial is for adults with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML), or low-blast acute myelogenous leukemia (AML). They should have certain risk scores based on their condition, be able to perform daily activities with minimal help, and not have had previous specific cancer treatments. People can't join if they've had another cancer in the last 2 years, severe infections, HIV/hepatitis B/C, heart problems within the past 6 months, or are on strong CYP3A inducers.Check my eligibility

What is being tested?

The study tests whether combining pevonedistat with azacitidine improves survival without disease progression compared to just azacitidine alone in patients. An 'event' refers to death or worsening of the disease. Patients will be randomly assigned to one of these treatment groups.See study design

What are the potential side effects?

Possible side effects include reactions at injection sites, blood cell count changes leading to increased infection risk or bleeding tendencies, gastrointestinal symptoms like nausea and vomiting, fatigue and weakness. Each patient's experience may vary.

PANTHER Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My condition is MDS or CMML and falls into a high-risk category.

Select...

I can take care of myself and am up and about more than half of my waking hours.

Select...

My AML is moderate and I have a high risk score for intensive chemotherapy.

Select...

I have been diagnosed with MDS, CMML, or low-blast AML with WBC under 13,000/mcL.

PANTHER Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to year 1

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to year 1

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

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Event-Free Survival (EFS)

Secondary outcome measures

Duration of Complete Remission (CR)

Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)

Duration of Overall Response (OR)

+26 more

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

Erythema

Aspartate aminotransferase increased

Hypomagnesaemia

Muscular weakness

Stomatitis

Urinary tract infection

Weight decreased

Pleural effusion

Dehydration

Musculoskeletal pain

Hypophosphataemia

Contusion

Pain in extremity

Productive cough

Non-cardiac chest pain Pain

Sepsis

Alanine aminotransferase increased

Hypoalbuminaemia

Hypocalcaemia

Hyponatraemia

Malaise

Nasal congestion

Non-cardiac chest pain

Oral candidiasis

Petechiae

Nasopharyngitis

Cellulitis

Cerebrovascular accident

Gastric haemorrhage

Atrial fibrillation

Congestive cardiomyopathy

Acute febrile neutrophilic dermatosis

Embolic stroke

Endocarditis

Failure to thrive

Gastrointestinal necrosis

Hepatic lesion

Lower respiratory tract infection

Lung infiltration

Multiple organ dysfunction syndrome

Myocardial infarction

Wound infection

Postoperative hypotension

Acute myeloid leukaemia

Ankle fracture

Arthritis

Arthritis reactive

Autoimmune haemolytic anaemia

Bacteraemia

Bacterial sepsis

Bronchopulmonary aspergillosis

Cauda equina syndrome

Cholecystitis

Drug hypersensitivity

Gastrointestinal ulcer perforation

Haematuria

Haemorrhage intracranial

Hypoxia

Influenza

Inguinal hernia

Ischaemic gastritis

Leukopenia

Myelodysplastic syndrome

Myelodysplastic syndrome transformation

Post procedural hypotension

Rectal haemorrhage

Renal colic

Respiratory tract infection

Soft tissue infection

Spinal compression fracture

Urinary tract infection enterococcal

Urinary tract obstruction

Lung infection

Chronic kidney disease

Death

Gastritis erosive

Supraventricular tachycardia

Thrombophlebitis superficial

100%

80%

60%

40%

20%

Study treatment Arm

Azacitidine 75 mg/m^2

Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2

PANTHER Trial Design

2Treatment groups

Experimental Treatment

Group I: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2Experimental Treatment2 Interventions

Azacitidine 75 mg/m^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.

Group II: Azacitidine 75 mg/m^2Experimental Treatment1 Intervention

Azacitidine 75 milligram per square meter (mg/m^2) intravenous (IV) or subcutaneous (SC) injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Azacitidine

2012

Completed Phase 3

~1440

Pevonedistat

2021

Completed Phase 2

~290

0 / 4Eligibility criteria met

Find a Location

Who is running the clinical trial?

Millennium Pharmaceuticals, Inc.Lead Sponsor

404 Previous Clinical Trials

46,460 Total Patients Enrolled

TakedaLead Sponsor

1,202 Previous Clinical Trials

4,177,808 Total Patients Enrolled

Takeda Development Center Americas, Inc.Industry Sponsor

56 Previous Clinical Trials

11,576 Total Patients Enrolled

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Are there any open appointments for this research project?

"This study, which was last updated on August 24th, 2022, is not currently recruiting patients for clinical trials. Although this study is not taking candidates at this time, there are 3034 other studies that are."

Answered by AI

What is the most severe reaction that people have had to Pevonedistat?

"Pevonedistat's Phase 3 status indicates that there is both efficacy data and multiple rounds of safety data, leading to a Power team safety estimate of 3."

Answered by AI

How many individuals can enroll in this research project?

"This study is no longer enrolling patients. The trial was first advertised on November 28th, 2017 and was last updated on August 24th, 2022. For those still searching for active trials, 2847 studies for leukemia, myelomonocytic, chronic and 187 for Pevonedistat are currently recruiting patients."

Answered by AI

For what reasons is Pevonedistat typically given to patients?

"Pevonedistat is an effective treatment against malignant neoplasms, 20-30% blasts, and neutropenia and/or thrombocytopenia."

Answered by AI

Is Pevonedistat a common medication in these types of studies?

"Pevonedistat is being studied in 187 different clinical trials, 33 of which are currently ongoing. The majority of these trials are located in Saint Louis, Missouri; however, there are 5,746 total locations running these trials."

Answered by AI

Recent research and studies

Blood AdvancesJournal

Pevonedistat Plus Azacitidine Vs Azacitidine Alone in Higher-risk Mds/chronic Myelomonocytic Leukemia or Low-blast-percentage AML

Adès, Lionel, Larisa Girshova, Vadim A. Doronin, María Díez-Campelo, David Valcárcel, Suman Kambhampati, Nora-Athina Viniou, et al.. 2022. “Pevonedistat Plus Azacitidine Vs Azacitidine Alone in Higher-risk Mds/chronic Myelomonocytic Leukemia or Low-blast-percentage AML”. Blood Advances. American Society of Hematology. doi:10.1182/bloodadvances.2022007334.

clinicaltrials.govStudy

Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

2017. "Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03268954.

All > Acute Myeloid Leukemia > Aml