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Nucleoside Metabolic Inhibitor

Tamibarotene + Venetoclax/Azacitidine for Acute Myeloid Leukemia

Phase 2

Waitlist Available

Research Sponsored by Syros Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

All participants must have obtained a blood sample for RARA biomarker investigational assay testing prior to starting treatment on Cycle 1 Day 1. The results of the investigational biomarker assay for all participants must be confirmed as RARA-positive by Cycle 1 Day 8 to enroll (Part 1) or to be randomized (Part 2) in the study.

Be older than 18 years old

Must not have

Prior treatment (before Cycle 1 Day 1) for the diagnosis of AML, myelodysplastic syndromes (MDS), or antecedent hematologic malignancy with any hypomethylating agent, venetoclax, chemotherapy, or hematopoietic stem cell transplantation (HSCT), with the exception of prior treatment with hydroxyurea.

Participants have APL.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial will test whether adding tamibarotene to the 2 other drugs helps people with this specific type of leukemia live longer.

Who is the study for?

This trial is for adults with newly diagnosed AML who can't start standard chemo due to age, health, or other issues. They must have a certain gene abnormality (RARA-positive) and not have had previous treatments for their leukemia except hydroxyurea.

What is being tested?

The study tests Tamibarotene combined with Venetoclax and Azacitidine in patients with acute myeloid leukemia (AML). It targets those whose cancer has the RARA gene overexpression and are unsuitable for standard chemotherapy.

What are the potential side effects?

Potential side effects may include typical reactions to cancer drugs such as nausea, fatigue, blood cell count changes leading to increased infection risk, liver function alterations, and possible bleeding complications.

Eligibility Criteria

Inclusion Criteria

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

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My blood test before treatment showed I am RARA-positive.

Exclusion Criteria

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

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I have not had specific treatments for AML, MDS, or other blood cancers before starting this trial, except for hydroxyurea.

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I have acute promyelocytic leukemia (APL).

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My acute myeloid leukemia has spread to my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

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

Treatment Details

Study Objectives

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

Primary study objectives

Part 2: CR/CRi Rate

Secondary study objectives

Part 1: Overall Response Rate (ORR)

Part 2: CR Rate

Part 2: CR/CRh Rate

+7 more

Side effects data

From 2023 Phase 2 trial • 155 Patients • NCT02807558

50%

Nausea

39%

Diarrhoea

36%

Constipation

32%

Decreased appetite

32%

Febrile neutropenia

32%

Fatigue

32%

Vomiting

29%

Hypertriglyceridaemia

25%

Epistaxis

25%

Arthralgia

21%

Pyrexia

21%

Dyspnoea

18%

Anaemia

18%

Dry skin

18%

Asthenia

18%

Weight decreased

18%

Petechiae

18%

Pruritus

18%

Fall

14%

Haematoma

14%

Chills

14%

Sepsis

14%

Dizziness

14%

Stomatitis

14%

Myalgia

14%

Oedema peripheral

11%

Nasal congestion

11%

Delirium

11%

Pneumonia

11%

Injection site pain

11%

Cough

11%

Pleural effusion

11%

Rales

11%

Contusion

11%

Atrial fibrillation

11%

Dysgeusia

11%

Headache

11%

Ear pain

11%

Abdominal pain

11%

Dry mouth

11%

Toothache

11%

Purpura

11%

Pollakiuria

11%

Pain in extremity

11%

Acute kidney injury

11%

Oral candidiasis

11%

Musculoskeletal pain

Sneezing

Anxiety

Insomnia

Abdominal distension

Urinary incontinence

Failure to thrive

Lethargy

Non-cardiac chest pain

Hypoxia

Upper-airway cough syndrome

Tachypnoea

Psychomotor retardation

Blood creatinine increased

Alanine aminotransferase increased

Aspartate aminotransferase increased

Blood bilirubin increased

Ear discomfort

Sinus tachycardia

Neutropenia

Thrombocytopenia

Leukopenia

Gastrooesophageal reflux disease

Angina bullosa haemorrhagica

Gingival pain

Alopecia

Rash maculo-papular

Muscular weakness

Neck pain

Urinary tract infection

Partial seizures

Pneumonia fungal

Device related infection

General physical health deterioration

Inflammatory pain

Respiratory acidosis

Pneumothorax

Nasal mucosal ulcer

Paraesthesia

Dyspepsia

Mouth ulceration

Periodontal disease

Rash

Skin mass

Dysuria

Bronchitis

Diverticulitis

Oesophageal candidiasis

Tooth abscess

Tremor

Lung disorder

Pneumonitis

Lung infection

Bacteraemia

Enterobacter pneumonia

Erysipelas

Proteus infection

Serratia sepsis

Streptococcal bacteraemia

Hypotension

Injection site nodule

Mucosal inflammation

Systemic inflammatory response syndrome

Dysphonia

Pleuritic pain

Cerebral haemorrhage

Leukostasis syndrome

Enteritis

Pancreatitis

Rectal haemorrhage

Injection site reaction

Localised oedema

Peripheral swelling

Oropharyngeal pain

Laryngeal haemorrhage

Lung consolidation

Pulmonary oedema

Balance disorder

Eschar

Face injury

Procedural pain

Transfusion-related circulatory overload

Macroglossia

Palpitations

Tachycardia

Cardiac arrest

Cardiac failure

Coronary artery insufficiency

Encephalopathy

Peripheral sensory neuropathy

Syncope

Hyperaesthesia

Parkinsonism

Somnolence

Lymph node pain

Thrombocytopenic purpura

Thymus disorder

Excessive cerumen production

Ocular hyperaemia

Oral pain

Lip swelling

Melaena

Mouth haemorrhage

Oral mucosal blistering

Blister

Micturition urgency

Scab

Stasis dermatitis

Urticaria

Joint range of motion decreased

Urinary hesitation

Back pain

Muscle spasms

Amyotrophy

Flank pain

Rash pustular

Fluid overload

Cystitis bacterial

Escherichia urinary tract infection

Oral fungal infection

Hypocalcaemia

Metabolic alkalosis

Squamous cell carcinoma of skin

Chest pain

Pulmonary mass

Lymphopenia

Skin erosion

Groin pain

Urinary tract infection enterococcal

100%

80%

60%

40%

20%

Study treatment Arm

R/R Non-APL AML: Tamibarotene and Azacitidine

LR-MDS: Tamibarotene Monotherapy

R/R Non-APL AML or R/R HR-MDS: Tamibarotene Monotherapy

R/R Non-APL AML or R/R HR-MDS: Tamibarotene and Daratumumab

Newly Diagnosed Non-APL AML: Tamibarotene Monotherapy

Newly Diagnosed Non-APL AML: Tamibarotene and Azacitidine

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Part 3: Tamibarotene/Venetoclax/AzacitidineExperimental Treatment3 Interventions

Part 2 participants treated with venetoclax/azacitidine who experience progressive disease, relapse after initial CR or CRi response, or treatment failure may begin subsequent treatment in Part 3, where tamibarotene will be added to their regimen.

Group II: Part 2: Tamibarotene/Venetoclax/AzacitidineExperimental Treatment3 Interventions

Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination at the dose and regimen selected in Part 1.

Group III: Part 1: Tamibarotene/Venetoclax/AzacitidineExperimental Treatment3 Interventions

Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 milligrams (mg)/square meter (m\^2) once daily, on Days 1 through 7 of each 28-day therapy cycle (per VIDAZA USPI). Alternative dosing of azacitidine (Days 1 through 5, 8, and 9) will be permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing is 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg twice daily (BID) orally, on Days 8 through 28 of each 28-day therapy cycle. Tamibarotene will only be administered to participants who have been confirmed as RARA-positive.

Group IV: Part 2: Venetoclax/AzacitidineActive Control2 Interventions

Participants will receive the venetoclax/azacitidine combination at the dose and regimen selected in Part 1.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tamibarotene

Not yet FDA approved

Azacitidine

2012

Completed Phase 3

~1440