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Alkylating agents

Oral Azacitidine + R-miniCHOP for Diffuse Large B-Cell Lymphoma

Phase 2 & 3

Recruiting

Led By Elizabeth A Brem

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Participants with Grade IIIB follicular lymphoma (FL) or high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are also eligible

Participants with DLBCL transformed from follicular lymphoma (FL) or marginal zone lymphoma (MZL, including mucosa-associated lymphoid tissue [MALT] lymphomas), lymphoplasmacytic lymphoma (LPL), or nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) are eligible

Must not have

Participants must not have any other known uncontrolled intercurrent illness

Participants must not have active inflammatory bowel disease, celiac disease, prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism, or excretion of the study drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of registration to date of first observation of progressive disease according to the 2014 lugano classification, or death due to any cause, assessed up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial compares side effects & activity of azacitidine & R-miniCHOP (monoclonal antibody, prednisone, 3 chemo drugs) in 75+ newly-diagnosed DLBCL patients. Combining azacitidine & R-miniCHOP may shrink the cancer or extend time w/o symptoms/survival compared to R-miniCHOP alone.

Who is the study for?

This trial is for people aged 75 or older with newly diagnosed diffuse large B cell lymphoma. They must have certain types of this cancer, adequate organ function, and no history of specific treatments for DLBCL. HIV-positive patients can join if their viral load is undetectable, but those with CNS involvement or certain gastrointestinal issues cannot participate.

What is being tested?

The study compares oral azacitidine plus R-miniCHOP (a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) against R-miniCHOP alone to see which is better at shrinking the cancer or extending symptom-free survival in elderly patients.

What are the potential side effects?

Possible side effects include reactions related to the immune system's response to rituximab, inflammation from prednisone use; and typical chemotherapy-related issues like nausea, fatigue, hair loss from doxorubicin; nerve damage from vincristine; and potential blood count changes.

Eligibility Criteria

Inclusion Criteria

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

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My lymphoma is advanced (Grade IIIB) or high-grade with specific genetic changes.

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My DLBCL cancer developed from another type of lymphoma.

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I can take care of myself and am up and about more than 50% of my waking hours.

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My kidneys work well enough, with a creatinine clearance of 30 ml/min or more.

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I agree to use contraception and not donate sperm during the trial.

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My lymphoma type is one of the specified eligible subtypes.

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My cancer did not develop from previous CLL.

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My liver, blood, and heart are functioning within normal ranges.

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I have been diagnosed with a specific type of lymphoma called DLBCL.

Exclusion Criteria

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

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I do not have any uncontrolled illnesses besides my cancer.

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I do not have any major gut issues that could affect how a drug works in my body.

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I do not have any ongoing infections that aren't under control.

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I have received less than 250 mg/m^2 of doxorubicin.

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My cancer has not spread to my brain or spinal cord.

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I have not had severe nerve pain or tingling in the last month.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of registration to date of first observation of progressive disease according to the 2014 lugano classification, or death due to any cause, assessed up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of registration to date of first observation of progressive disease according to the 2014 lugano classification, or death due to any cause, assessed up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of registration to date of first observation of progressive disease according to the 2014 lugano classification, or death due to any cause, assessed up to 1 year for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Excess toxicity as a result of adding oral azacitidine (CC-486) to reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) (Safety run-in)

Overall survival (Phase III)

Progression-free survival (PFS) (Phase II)

Secondary study objectives

Incidence of adverse events

Metabolic complete response (CR)

Other study objectives

Changes in function (Integrated Correlative Geriatric Assessments Substudy)

Frailty status (Integrated Correlative Geriatric Assessments Substudy)

Frailty status (fit/unfit vs frail) (Integrated Correlative Geriatric Assessments Substudy)

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

Abdominal pain upper

Escherichia sepsis

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

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm I (oral azacitidine, R-miniCHOP)Experimental Treatment8 Interventions

Patients receive CC-486 PO for 7 days prior to cycle 1. Patients then receive CC-486 PO on days 8-21. Treatment repeats every 21 days for cycles 1-5 in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV (or SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for cycles 1-6 (6 cycles total) in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

Group II: Arm II (R-miniCHOP)Active Control7 Interventions

Patients receive rituximab IV (or SC for cycles 2-6), cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Oral Azacitidine

2013

Completed Phase 3

~950

Biospecimen Collection

2004

Completed Phase 3

~2030