What is the mechanism of action of this treatment?

Azacitidine, a common treatment for Large Granular Lymphocyte Leukemia (LGL), works by incorporating into DNA and RNA, inhibiting DNA methyltransferase, and causing DNA hypomethylation. This reactivates tumor suppressor genes and induces cancer cell death. Additionally, it disrupts RNA and protein synthesis, leading to cell death. These mechanisms are vital for LGL patients as they target the rapid division and spread of malignant cells, aiming to reduce the leukemic cell burden and improve patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for Large Granular Lymphocyte Leukemia, particularly those similar to oral azacitidine, often result in side effects such as neutropenia, thrombocytopenia, and anemia. Patients may also experience gastrointestinal symptoms like nausea, vomiting, and diarrhea, as well as increased susceptibility to infections and general fatigue. These side effects reflect the typical toxicities associated with chemotherapy drugs that target cancer cells by killing them, stopping their division, or preventing their spread.

What prior FDA approvals exist?

The FDA has not specifically approved oral azacitidine for the treatment of Large Granular Lymphocyte Leukemia (LGL). However, azacitidine, a chemotherapy drug, is being studied for its potential benefits in treating relapsed or refractory T-cell LGL. Azacitidine works by killing cancer cells, stopping them from dividing, or preventing them from spreading. Other treatments for LGL may include immunosuppressive therapies and other chemotherapeutic agents, but specific FDA approvals for LGL are limited.

What other types of research exist?

Promising novel alternatives to oral azacitidine for Large Granular Lymphocyte Leukemia patients include venetoclax, which is a potent BCL-2 inhibitor showing efficacy in various leukemias, and BTK inhibitors like ibrutinib or zanubrutinib, which have demonstrated benefits in chronic lymphocytic leukemia and other lymphoid malignancies. These agents offer targeted mechanisms that may provide effective treatment options for LGL patients.

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Anti-metabolites

Oral Azacitidine for Leukemia

Phase 1 & 2

Recruiting

Led By Jonathan Brammer, MD

Research Sponsored by John Reneau

Eligibility Criteria Checklist

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

Must have

Symptomatic anemia with hemoglobin < 10 g/dL

Transfusion-dependent anemia

Must not have

Prior use of 5-azacytidine or decitabine

Active Infection requiring ongoing anti-microbial treatment. Patients with human immunodeficiency virus (HIV), positive hepatitis B surface antigen or hepatitis C antibody will be excluded

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the best dose and effects of oral azacitidine in patients with T-cell large granular lymphocytic leukemia that has come back or did not respond to previous treatments. Azacitidine is a chemotherapy drug that stops cancer cells from growing, dividing, or spreading.

Who is the study for?

Adults with relapsed or refractory T-cell large granular lymphocytic leukemia who need treatment and have not used certain drugs like 5-azacytidine. They must be able to consent, have a decent performance status, meet specific blood count criteria, agree to use birth control, and be off previous treatments for a set time. Those with active infections or on immune-suppressive therapy (beyond low-dose prednisone) are excluded.

What is being tested?

The trial is testing oral Azacitidine to find the best dose and assess its benefits/side effects in patients whose T-cell large granular lymphocytic leukemia has returned after treatment or didn't respond at all. It's a phase I/II study which means they're looking at safety as well as how well it works.

What are the potential side effects?

Oral Azacitidine may cause side effects such as nausea, vomiting, diarrhea, constipation, loss of appetite; fatigue; muscle or joint pain; injection site reactions if given subcutaneously; and lowered blood cell counts leading to increased risk of infection.

Eligibility Criteria

Inclusion Criteria

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

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My hemoglobin is below 10 g/dL and I feel very tired.

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I need regular blood transfusions for my anemia.

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I have tried at least one treatment for my condition and stopped it more than 14 days ago or 5 half-lives ago, whichever is longer.

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I need treatment for T-LGL leukemia.

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I am 18 years old or older.

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I can take care of myself and perform daily activities.

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I have low white blood cell counts and get infections often.

Exclusion Criteria

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

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I have previously used 5-azacytidine or decitabine.

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I do not have an active infection needing treatment, nor HIV or hepatitis B/C.

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

Overall response rate (complete response [CR] + partial response [PR]) (Phase II)

Side effects data

From 2023 Phase 3 trial • 216 Patients • NCT01566695

76%

Nausea

68%

Diarrhoea

63%

Vomiting

49%

Neutropenia

47%

Constipation

28%

Pyrexia

27%

Thrombocytopenia

27%

Febrile neutropenia

27%

Oedema peripheral

26%

Epistaxis

25%

Decreased appetite

23%

Asthenia

21%

Fatigue

20%

Petechiae

18%

Anaemia

15%

Cough

14%

Contusion

13%

Abdominal pain

12%

Dyspnoea

12%

Back pain

11%

Urinary tract infection

11%

Hypokalaemia

Leukopenia

Weight decreased

Insomnia

Pneumonia

Mouth haemorrhage

Hypomagnesaemia

Haematoma

Anxiety

Alanine aminotransferase increased

Arthralgia

Sepsis

Dizziness

Gingival bleeding

Upper respiratory tract infection

Pain in extremity

Depression

Confusional state

Septic shock

Gastrooesophageal reflux disease

Cellulitis

Oral herpes

Serum ferritin increased

Hyperglycaemia

Iron overload

Ecchymosis

Hypotension

Neutropenic sepsis

Fall

Lung infection

General physical health deterioration

Cardiac failure congestive

Tachyarrhythmia

Bone marrow failure

Cardiac failure

Multiple organ dysfunction syndrome

Cholecystitis

Hyperbilirubinaemia

Atypical pneumonia

Bronchopulmonary aspergillosis

Subdural haematoma

Haemorrhage intracranial

Acute kidney injury

Renal failure

Febrile infection

Epididymitis

Gastroenteritis

Prerenal failure

Gastritis

Corona virus infection

Pancytopenia

Escherichia sepsis

Abdominal pain upper

Myocardial infarction

Renal colic

Chronic kidney disease

Lethargy

Groin abscess

Lower respiratory tract infection

Device related infection

Influenza

Klebsiella infection

Haemolytic anaemia

Haemorrhagic anaemia

Acute myocardial infarction

Angina unstable

Atrial fibrillation

Gastrointestinal haemorrhage

Intestinal obstruction

Intestinal perforation

Neutropenic colitis

Oesophageal achalasia

Oral mucosal blistering

Rectal haemorrhage

Gait disturbance

Hypothermia

Abscess limb

Arteriovenous fistula site infection

Klebsiella sepsis

Meningitis

Meningitis bacterial

Myringitis

Pneumonia fungal

Pneumonia pneumococcal

Pseudomonal sepsis

Pulmonary mycosis

Respiratory tract infection

Skin infection

Staphylococcal infection

Urinary tract infection bacterial

Viral sepsis

Periorbital haematoma

Febrile nonhaemolytic transfusion reaction

Head injury

Hip fracture

Subdural haemorrhage

Upper limb fracture

Dehydration

Diabetes mellitus inadequate control

Diabetic metabolic decompensation

Hyperkalaemia

Hypoglycaemia

Muscular weakness

Polychondritis

Acute myeloid leukaemia

Bone neoplasm

Bowen's disease

Colon adenoma

Mantle cell lymphoma recurrent

Spinal cord neoplasm

Central nervous system lesion

Transient ischaemic attack

Epilepsy

Generalised tonic-clonic seizure

Acute respiratory distress syndrome

Pleural effusion

Pleurisy

Pneumonia aspiration

Pulmonary embolism

Respiratory failure

Hypersensitivity vasculitis

Rash

Rash generalised

Shock haemorrhagic

Cardiogenic shock

Intra-abdominal haemorrhage

Status epilepticus

Syncope

Urinary retention

Prostatitis

100%

80%

60%

40%

20%

Study treatment Arm

Oral Azacitidine Plus Best Supportive Care

Placebo Plus Best Supportive Care

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: Treatment (Oral Azacitidne)Experimental Treatment1 Intervention

Patients will receive CC-486 orally (PO) D1-14 of a 28-day cycle, in a similar fashion to the QUAZAR study for a minimum of 4 cycles. Patients that achieve a response (CR or PR) will remain on study for a maximum of 12 months. Patients without a response at 4 months will come off the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Oral Azacitidine

2013

Completed Phase 3

~950

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Azacitidine, a common treatment for Large Granular Lymphocyte Leukemia (LGL), works by incorporating into DNA and RNA, inhibiting DNA methyltransferase, and causing DNA hypomethylation. This reactivates tumor suppressor genes and induces cancer cell death. Additionally, it disrupts RNA and protein synthesis, leading to cell death. These mechanisms are vital for LGL patients as they target the rapid division and spread of malignant cells, aiming to reduce the leukemic cell burden and improve patient outcomes.

First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia.