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Monoclonal Antibodies

Canakinumab + Darbepoetin Alfa for Myelodysplastic Syndrome

Phase 1 & 2

Recruiting

Led By David A Sallman, MD

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

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

Must have

Documented diagnosis of MDS by World Health Organization (WHO) criteria, further meeting the following criteria according to disease risk classification

Patients must be transfusion dependent, defined as requirement for transfusion of at least 3 units of Packed Red Blood cells (PRBCs) 16 weeks for a Hgb<9.0g/dL or, in non-transfusion dependent patients (<3 units of PRBCs transfused in the preceding 16 weeks), must have a baseline Hgb of <9.0 g/dL at time of study enrollment

Must not have

Previous treatment with a hypomethylating agent (such as azacitidine, decitabine or investigational hypomethylating agent)

Patient has any of the following cardiac abnormalities: (a) Uncontrolled, symptomatic congestive heart failure as designated by the treating physician (b) Myocardial infarction ≤ 6 months prior to enrollment (c) Unstable angina pectoris as designated by the treating physician (d) Serious uncontrolled cardiac arrhythmia as designated by the treating physician. (e) Uncontrolled hypertension as designated by the treating physician

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination treatment for patients with a blood disorder who have failed other treatments.

Who is the study for?

This trial is for patients with lower-risk Myelodysplastic Syndrome (MDS) who didn't respond to previous Erythropoietin Stimulating Agent treatment. Participants must have adequate organ function, be transfusion dependent or have low hemoglobin levels, and not be pregnant or breastfeeding. They should agree to use contraception and cannot have had certain heart conditions, other cancers within 2 years, or treatments like hypomethylating agents.

What is being tested?

The study tests the combination of Canakinumab Injection with Darbepoetin Alfa in MDS patients who failed prior ESA therapy. It's an open-label Phase 1b/2 trial assessing both the safety (toxicity) and effectiveness (efficacy) of this drug combo.

What are the potential side effects?

Potential side effects may include allergic reactions to the drugs' components, increased risk of infections due to immune system suppression by Canakinumab, and typical medication-related issues such as fatigue, nausea, or headaches.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with MDS according to WHO standards.

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I need blood transfusions regularly or my hemoglobin is below 9.0 g/dL.

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I can take care of myself and perform daily activities.

Exclusion Criteria

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

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I have been treated with a drug that changes how my genes work.

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I have serious heart problems as diagnosed by my doctor.

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I have a history of HIV, Hepatitis B, or Hepatitis C.

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I do not have active or untreated latent tuberculosis.

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I have had a bone marrow or organ transplant for a blood disorder or other disease.

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I haven't taken TNF or IL-1 targeting drugs in the last 28 days.

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I have not received a live-virus vaccine in the last 30 days.

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I am allergic to darbepoetin alfa or components of the study drug.

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I am pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 60 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1b: Maximum Tolerated Dose (MTD)

Phase 2: Rate of Hematologic Improvement-Erythroid (HI-E) response

Secondary study objectives

Phase 1b and Phase 2: Degree in reduction of PRBC Transfusions

Phase 1b and Phase 2: Duration of Hematologic Improvement-Erythroid (HI-E) response

Phase 2: Duration of Response

+3 more

Side effects data

From 2017 Phase 4 trial • 2825 Patients • NCT00773513

32%

Hypertension

19%

Diarrhoea

16%

Procedural hypotension

14%

Muscle spasms

14%

Urinary tract infection

13%

Nasopharyngitis

13%

Bronchitis

13%

Pneumonia

12%

Anaemia

11%

Arteriovenous fistula site complication

11%

Hyperparathyroidism secondary

11%

Cough

10%

Hyperphosphataemia

10%

Headache

10%

Constipation

Arthralgia

Upper respiratory tract infection

Vomiting

Pain in extremity

Hypotension

Hyperkalaemia

Atrial fibrillation

Pruritus

Fluid overload

Back pain

Dyspnoea

Gastroenteritis

Nausea

Abdominal pain

Insomnia

Pyrexia

Abdominal pain upper

Oedema due to renal disease

Asthenia

Dizziness

Osteoarthritis

Arteriovenous fistula thrombosis

Cataract

Depression

Sepsis

Respiratory tract infection

Lower respiratory tract infection

Influenza

Musculoskeletal pain

Acute myocardial infarction

Oedema peripheral

Dyspepsia

Cardiac arrest

Myocardial infarction

Epistaxis

Death

Sudden death

Septic shock

Peritonitis

Acute coronary syndrome

Angina unstable

Transient ischaemic attack

Angina pectoris

Cardiac failure

Arteriovenous graft thrombosis

Gangrene

Gastrointestinal haemorrhage

Cellulitis

Femur fracture

Arteriovenous fistula site haemorrhage

Peripheral ischaemia

Peripheral arterial occlusive disease

Cerebrovascular accident

Pleural effusion

End stage renal disease

Arteriovenous fistula site infection

Musculoskeletal chest pain

Non-cardiogenic pulmonary oedema

Chronic obstructive pulmonary disease

Cholelithiasis

Cardiopulmonary failure

Haematoma

Coronary artery disease

Myocardial ischaemia

Steal syndrome

Staphylococcal infection

Orthostatic hypotension

Syncope

Cerebral haemorrhage

General physical health deterioration

Chest pain

Respiratory failure

Basal cell carcinoma

Device related sepsis

Staphylococcal sepsis

Bacteraemia

Viral infection

Bradycardia

Atrioventricular block complete

Coronary artery stenosis

Femoral neck fracture

Gastric ulcer

Inguinal hernia

Cholecystitis

Peripheral vascular disorder

Subdural haematoma

Hypertensive crisis

Peripheral artery stenosis

Confusional state

Infection

Diabetic foot infection

Erysipelas

Cardiac failure acute

Hip fracture

Rib fracture

Large intestine polyp

Rectal haemorrhage

Hypoglycaemia

Cachexia

Device malfunction

Device related infection

Cardiac failure congestive

Cardio-respiratory arrest

Aortic valve stenosis

Multiple fractures

Extremity necrosis

Ischaemic stroke

Cerebral infarction

Pulmonary oedema

Acute pulmonary oedema

Pneumonia aspiration

Renal impairment

Haematuria

Skin ulcer

Diabetic foot

Thrombosis in device

Urosepsis

100%

80%

60%

40%

20%

Study treatment Arm

Methoxy Polyethylene Glycol-Epoetin Beta

Erythropoiesis Stimulating Agents

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase 2: Treatment at Maximum Tolerated DoseExperimental Treatment2 Interventions

Patients will be treated with Darbepoetin alfa subcutaneously at a dose of 300 mg on days 1 and 15 of each cycle plus the maximum tolerated dose of Canakinumab.

Group II: Phase 1b: Dose Level 2Experimental Treatment2 Interventions

Patients will be treated at dose level 2: Canakinumab 300 mg by subcutaneous injection on day 1 of each 28 day cycle. Darbepoetin alfa will be administered subcutaneously at a dose of 300mg on days 1 and 15 of each cycle.

Group III: Phase 1b: Dose Level 1Experimental Treatment2 Interventions

Patients will be treated at dose level 1: Canakinumab 150 mg by subcutaneous injection on day 1 of each 28 day cycle. Darbepoetin alfa will be administered subcutaneously at a dose of 300mg on days 1 and 15 of each cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Darbepoetin Alfa

2008

Completed Phase 4

~5950

0 / 12Eligibility criteria met