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DNA Methyltransferase Inhibitor

Venetoclax + Azacitidine for Myeloproliferative Disorders

Phase 2

Recruiting

Led By Vikas Gupta, M.D.

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

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

Must have

Documented diagnosis per World Health Organization (WHO) 2016 criteria of BCR-ABL negative myeloproliferative neoplasms (MPN)

Female participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to cycle 1 day 1

Must not have

History of allogeneic stem cell transplant for MPN

History of prior blast-reduction therapy for AP/BP-MPN

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial will study the safety and efficacy of azacitidine and venetoclax in people with BRC-ABL negative myeloproliferative neoplasms.

Who is the study for?

This trial is for adults with advanced BCR-ABL negative myeloproliferative neoplasms who haven't had blast reduction therapy for their condition. They should be able to perform daily activities with ease to moderate difficulty (ECOG 0-2) and have good organ function. Participants must not be pregnant, breastfeeding, or have a recent history of other cancers or serious health conditions that could affect study participation.

What is being tested?

The study tests the safety and effectiveness of combining two drugs, Venetoclax and Azacitidine, in treating accelerated or blast phase myeloproliferative neoplasms. It aims to understand how well these drugs work together for patients who haven't received prior treatment specifically aimed at reducing blasts in their blood.

What are the potential side effects?

Potential side effects may include nausea, vomiting, diarrhea, low blood counts leading to increased infection risk or bleeding problems, fatigue, liver issues and potential drug interactions affecting heart rhythm or other medications.

Eligibility Criteria

Inclusion Criteria

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

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My blood disorder diagnosis follows WHO 2016 criteria and is not caused by the BCR-ABL gene.

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I am a woman who can have children and have a negative pregnancy test within the last 14 days.

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I am able to get out of my bed or chair and move around.

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My blood disorder has worsened without having received specific treatment for this advanced stage.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a stem cell transplant from a donor for my blood disorder.

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I have had treatment to reduce blood cell precursors for myeloproliferative neoplasm.

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My leukemia has spread to my brain or spinal cord.

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I have an infection that isn't getting better despite treatment.

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I have a history of MDS, CMML, or other related blood disorders.

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I do not have active HIV, HBV, or HCV infections.

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My cancer has a specific genetic feature (t 15;17).

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I have had a heart attack in the last 3 months.

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I currently have an active COVID-19 infection.

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I have not had any active cancer in the last 2 years.

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I have been treated with venetoclax, navitoclax, azacytidine, or similar drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

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

Arthralgia

Back pain

Bronchitis

Insomnia

Upper respiratory tract infection

Hypertension

Weight decreased

Contusion

Haemorrhoids

Erythema

Urinary tract infection

Lethargy

Abdominal pain upper

Muscle spasms

Gingival bleeding

Injection site rash

Influenza

Oral candidiasis

Rhinitis

Pain in extremity

Hypotension

Dyspepsia

Injection site haematoma

Hypokalaemia

Haematuria

Pharyngolaryngeal pain

Chest pain

Mouth ulceration

Musculoskeletal pain

Depression

Oedema

Pharyngitis

Anxiety

Ecchymosis

Injection site bruising

Injection site induration

Dyspnoea exertional

Pain

Bone pain

Alopecia

Skin lesion

Conjunctival haemorrhage

Respiratory tract infection

Tachycardia

Productive cough

Stomatitis

Dry mouth

Gingivitis

Chills

Sinusitis

Sepsis

Fall

Alanine aminotransferase increased

Sleep disorder

Gastritis

Neutropenic sepsis

Purpura

Catheter site haematoma

Muscular weakness

Nasal congestion

Hyperuricaemia

Cardiac failure

Bronchopneumonia

Lymphopenia

Gastrooesophageal reflux disease

Rectal haemorrhage

General physical health deterioration

Pallor

Septic shock

Myelodysplastic syndrome

Cerebral haemorrhage

Pitting oedema

Procedural pain

Syncope

Mouth haemorrhage

Gastrointestinal pain

Perianal abscess

Haemorrhoidal haemorrhage

Ventricular tachycardia

Anal haemorrhage

Lung infection

Subileus

Myocardial infarction

Oral soft tissue disorder

Catheter site haemorrhage

Hypophosphataemia

Renal colic

Hypoxia

Strabismus

Cellulitis

Eye Haemorrhage

Peripheral vascular disorder

Enterobacter infection

Gastrointestinal haemorrhage

Tooth abscess

Food poisoning

Intestinal haemorrhage

Clostridium difficile colitis

Delirium

Musculoskeletal chest pain

Pancytopenia

Endophthalmitis

Haematemesis

Tooth disorder

Meningitis

Subcutaneous abscess

Confusional state

Benign prostatic hyperplasia

Psychotic disorder

Abdominal discomfort

Atrial fibrillation

Angle closure glaucoma

Corynebacterium infection

Conjunctivitis

Fungal skin infection

Angina pectoris

Herpes zoster

Salmonella sepsis

Subdiaphragmatic abscess

Blood lactate dehydrogenase increased

Ocular hyperaemia

Catheter site pain

Joint swelling

Transient ischaemic attack

Pulmonary embolism

Pleural effusion

Cardiac failure acute

Vertigo

Oesophageal carcinoma

Myopia

Retinal artery occlusion

Squamous cell carcinoma of skin

Haemoptysis

Lung infiltration

Respiratory failure

Pulmonary oedema

Pulmonary fibrosis

Hallucination

Colitis ulcerative

Injection site nodule

Bacteraemia

Bile duct stone

Hepatic function abnormal

Fungal sepsis

Gasteroenteritis

Gasteroenteritis salmonella

Laryngopharyngitis

Lobar pneumonia

Lower respiratory tract infection

Pulmonary tuberculosis

Sialoadenitis

Splenic abscess

Staphylococcal bacteraemia

Clavicle fracture

Hip fracture

Traumatic intracranial haemorrhage

Diabetes mellitus

Colon cancer

Lung adenocarcinoma

Neoplasm prostate

Urinary tract neoplasm

Coma

Haemorrhage intracranial

Renal failure

Urethral stenosis

Acute pulmonary oedema

Acute respiratory failure

Hypoalbuminaemia

Hyponatraemia

Lymphadenopathy

Gingival pain

Generalised oedema

Catheter related infection

Neck pain

Dermatitis allergic

Rash macular

Urticaria

Bone marrow failure

Pericardial effusion

Hypothyroidism

Retinal Haemorrhage

Retinal tear

Abdominal wall abscess

Abscess neck

Ear infection

Enterobacter bacteraemia

Mucormycosis

Neutropenic infection

Parotitis

Pneumonia fungal

Synovial rupture

Osteoporosis

Myelofibrosis

Loss of consciousness

Urinary retention

Pneumonitis

Actinic keratosis

Aortic aneurysm

Circulatory collapse

Bronchopulmonary aspergillosis

Bradycardia

Aphthous stomatitis

Mucosal inflammation

Staphylococcal infection

Viral upper respiratory tract infection

Scratch

Thermal burn

Aspartate aminotransferase increased

Hypocalcaemia

Bursitis

Sinus headache

Chromaturia

Proteinuria

Pleurisy

Rash papular

Rash pruritic

100%

80%

60%

40%

20%

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

1Treatment groups

Experimental Treatment

Group I: Azacitidine and VenetoclaxExperimental Treatment2 Interventions

A treatment cycle is 28 days long. Azacitidine will be given by injection under the skin, once a day, for the first 6 days of every cycle. Venetoclax will be given orally, once a day, as follows at the discretion of their study doctors: Cycle 1: * Day 1 - 100 mg * Day 2 - 200 mg * Days 3 to 28 - 400 mg Cycle 2: * Participants with a response to the study drugs will continue taking 400 mg from Days 1 to 21, with no study drug from Days 22 to 28 during Cycle 2. * Participants who have not yet responded to the study drugs will continue taking 400 mg from Days 1 to 28 during Cycle 2. Cycle 3 and subsequent cycles: * Participants with a response to the study drugs will continue to take 400 mg from Days 1 to 21, with no study drug from Days 22 to 28. * Participants whose disease has not worsened will continue taking 400 mg from Days 1 to 28. * Participants have not responded to the study drugs will be withdrawn from the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

2019

Completed Phase 3

~2240

Azacitidine

2012

Completed Phase 3

~1440