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Alkylating agents

Ibrutinib + FCR for Chronic Lymphocytic Leukemia (iFCR Trial)

Phase 2

Waitlist Available

Led By Matthew Davids, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

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

Must have

Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as per IW-CLL 2008 criteria. Patients must also require therapy for that diagnosis, based on meeting at least one of the following criteria: evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x 10^9/L); massive (≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly; massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy; progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT of <6 months. Lymphocyte doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of <30 x 10^9/L, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded; autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy; documented constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs: unintentional weight loss >10% within 6 months prior to screening; significant fatigue (inability to work or perform usual activities); fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection; night sweats for more than 1 month prior to screening without evidence of infection; no prior CLL-directed therapy that was instituted due to patient previously meeting IW-CLL 2008 criteria for treatment; age greater than or equal to 18 years and less than or equal to 65. Because CLL is extremely rare in persons <18 years of age, children are excluded from this study. Because iFCR is an aggressive therapy that is likely to be less well-tolerated even in fit elderly subjects, persons > 65 years of age are excluded; ECOG performance status ≤ 1; adequate hematologic function independent of growth factor support for at least 7 days prior to screening and randomization, with the exception of pegylated G-CSF (pegfilgrastim) and darbepoetin which cannot be administered within 14 days of screening; patients must meet the following hematologic criteria at screening: absolute neutrophil count ≥ 750 cells/mm3 (0.75 x 109/L); platelet count ≥ 50,000 cells/mm3 (50 x 109/L); hemoglobin ≥ 8 g/L; adequate hepatic and renal function defined as: serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN); bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin); adequate renal function defined by serum creatinine >1.5 x ULN; PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN; the effects of ibrutinib on the developing human fetus are unknown. For this reason and because similar agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

significant fatigue (inability to work or perform usual activities)

Must not have

Any uncontrolled active systemic infection.

Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ibrutinib in combo with FCR as a possible treatment for CLL.

Who is the study for?

Adults aged 18-65 with confirmed chronic lymphocytic leukemia or small lymphocytic lymphoma who need treatment based on specific criteria like worsening anemia, significant weight loss, fatigue, fevers without infection, and night sweats. They should not have had previous CLL therapy and must be able to perform daily activities (ECOG ≤1). Adequate blood counts and liver/renal function are required. Participants must use effective contraception.

What is being tested?

The trial is testing a new drug combination for treating Chronic Lymphocytic Leukemia (CLL). It involves adding the drug Ibrutinib to the standard FCR regimen (Fludarabine, Cyclophosphamide, Rituximab) to see if it improves outcomes in younger patients who haven't been treated before.

What are the potential side effects?

Possible side effects include diarrhea, bleeding problems due to low platelets, infections from low white blood cell count, fatigue from anemia or the drugs themselves. Liver issues might arise shown by abnormal blood tests. Allergic reactions during infusion of Rituximab can also occur.

Eligibility Criteria

Inclusion Criteria

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

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I am too tired to work or do my usual activities.

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I have lost more than 10% of my weight without trying in the last 6 months.

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I am fully active and can carry on all my pre-disease activities without restriction.

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My kidney function is within normal limits based on my creatinine levels.

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I have not received treatment for CLL based on specific criteria.

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I have had night sweats for over a month without being sick.

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I have had fevers over 100.5°F or 38.0°C for more than 2 weeks without signs of infection.

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My blood tests show worsening anemia or low platelets.

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I am between 18 and 65 years old.

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I have been diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma.

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I have very large or worsening swollen lymph nodes.

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My spleen is very large, getting bigger, or causing symptoms.

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 ongoing infections that aren’t being treated.

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I cannot take pills due to issues with my stomach or intestines.

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I am not taking strong CYP3A inhibitors or inducers.

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My cancer has spread to my brain.

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I have HIV or active hepatitis but meet the specific testing requirements for enrollment.

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My leukemia has an unmutated IGHV and complex genetic changes.

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I have not had major surgery in the last 4 weeks.

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My tests show a specific genetic change in at least 20% of my cells.

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My early-stage cancer was treated successfully with no signs of disease.

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I haven't taken strong immune system suppressants or more than 20 mg/day of prednisone in the last 28 days.

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I had skin cancer (not melanoma) treated and currently show no signs of it.

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I have a bleeding disorder such as von Willebrand's disease or hemophilia.

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I cannot take preventive treatment for pneumocystis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 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

Part I: Participants Who Achieve a Minimal Residual Disease (MRD) Negative Complete Response (CR) in the Bone Marrow at 2 Months Post FCR

Part II: Participants Who Achieve a Minimal Residual Disease (MRD) Negative Complete Response (CR) in the Bone Marrow at 2 Years Post Discontinuation of Ibrutinib After Having Achieved MRD Negative CR at the 2 Months Post FCR Timepoint

Secondary study objectives

1-year Combined Response With MRD From Bone Marrow

Complete Response Rate (CRR)

Median Overall Survival (OS)

+8 more

Side effects data

From 2022 Phase 3 trial • 201 Patients • NCT03053440

37%

Diarrhoea

32%

Upper respiratory tract infection

29%

Muscle spasms

28%

Contusion

24%

Arthralgia

24%

Hypertension

22%

Oedema peripheral

22%

Anaemia

21%

Epistaxis

20%

Cough

19%

Rash

19%

Fatigue

18%

Back pain

18%

Atrial fibrillation

17%

Urinary tract infection

16%

Neutropenia

16%

Thrombocytopenia

15%

Nausea

15%

Headache

15%

Vomiting

14%

Pneumonia

14%

Dizziness

13%

Haematuria

12%

Peripheral swelling

12%

Pyrexia

12%

Constipation

11%

Localised infection

10%

Pain in extremity

10%

Onychoclasis

10%

Fall

10%

Oropharyngeal pain

10%

Lower respiratory tract infection

10%

Sinusitis

10%

Palpitations

Insomnia

Nasopharyngitis

Hyperuricaemia

Dyspnoea

Haematoma

Skin laceration

Paraesthesia

Dyspepsia

Dry skin

Cellulitis

Conjunctivitis

Skin infection

Iron deficiency

Anxiety

Rhinitis

Cataract

Conjunctival haemorrhage

Pruritus

Hypokalaemia

Syncope

Vision blurred

Abdominal pain

Abdominal pain upper

Nail infection

Neck pain

Purpura

Asthenia

Abdominal discomfort

Chest pain

Gingival bleeding

Mouth ulceration

Stomatitis

Onychomycosis

Rhinorrhoea

Actinic keratosis

Dermatitis

Petechiae

Influenza like illness

COVID-19

Gastroenteritis

Tooth infection

Limb injury

Squamous cell carcinoma of skin

Peripheral sensory neuropathy

Rosacea

Increased tendency to bruise

Gout

Basal cell carcinoma

Folliculitis

Oral herpes

Gastrooesophageal reflux disease

Retinal haemorrhage

Angina pectoris

Dry mouth

Vertigo

Haemorrhoids

Ecchymosis

Sepsis

Chills

Bronchitis

Furuncle

Joint injury

Blood alkaline phosphatase increased

Neutrophil count decreased

Decreased appetite

Joint swelling

Depression

Productive cough

Skin ulcer

Atrial flutter

Hyperglycaemia

Herpes zoster

Bladder transitional cell carcinoma

Abdominal distension

Tinnitus

Rotator cuff syndrome

Sinus bradycardia

Inguinal hernia

Dysphagia

Dry eye

Dysuria

Pollakiuria

Hypoalbuminaemia

Osteoporosis

Erythema

Acute myocardial infarction

Malaise

Cystitis

Alanine aminotransferase increased

Gamma-glutamyltransferase increased

Musculoskeletal chest pain

Seborrhoeic keratosis

Neuralgia

Benign prostatic hyperplasia

Dyspnoea exertional

Nasal congestion

Pneumonitis

Psoriasis

Skin fissures

Skin lesion

Laryngitis

Respiratory tract infection

Bradycardia

Acute kidney injury

Wound infection

Myalgia

Skin toxicity

Ear infection

Paronychia

Osteoarthritis

Pericarditis

Sciatica

Ocular hyperaemia

Nail disorder

Pleural effusion

Rectal haemorrhage

Cholecystitis

COVID-19 pneumonia

Drug withdrawal syndrome

Seasonal allergy

Vitamin D deficiency

Rash maculo-papular

Hypotension

Death

Loss of consciousness

Post procedural haemorrhage

Laryngeal oedema

Stress fracture

Lumbar vertebral fracture

Haemolytic anaemia

Haemorrhagic disorder

Viral infection

Wound infection staphylococcal

Cardiac failure acute

Wheezing

Colitis

Oral blood blister

Upper gastrointestinal haemorrhage

Drug-induced liver injury

Bacterial sepsis

Brain abscess

Device related infection

Gastrointestinal infection

Neurocryptococcosis

Septic shock

Streptococcal bacteraemia

Femoral neck fracture

Femur fracture

Subdural haematoma

Lethargy

Subarachnoid haemorrhage

Chronic kidney disease

Urinary bladder haemorrhage

Prostatitis

Acute pulmonary oedema

Hyponatraemia

Muscular weakness

Rash erythematous

Hyperviscosity syndrome

Melaena

Clostridium difficile infection

Post procedural sepsis

Pyelonephritis

Cerebrovascular accident

Respiratory disorder

Lymphadenopathy

Streptococcal sepsis

Amyloidosis

Influenza

Pneumonia viral

Coronary artery disease

Pericardial haemorrhage

Urosepsis

Spinal stenosis

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Ibrutinib

Arm B: Zanubrutinib

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: IbrutinibExperimental Treatment4 Interventions

- Ibrutinib- * Oral, daily during each cycle * fludarabine-administered at standard dosing for up to 6 cycles * cyclophosphamide-administered at standard dosing for up to 6 cycles * rituximab-administered at standard dosing for up to 6 cycles

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibrutinib

2014

Completed Phase 4

~2060

Fludarabine

2012

Completed Phase 4

~1860