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Monoclonal Antibodies

Daratumumab + Ibrutinib for Chronic Lymphocytic Leukemia

Phase 2

Waitlist Available

Led By Sikander Ailawadhi, M.D.

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

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

Must have

Patients must have relapse or refractory CLL/SLL who have received at least 1 prior anti-CLL/small lymphocytic lymphoma (SLL) therapy. (Note: There is no upper limit of how many lines of therapy the patient may have received previously)

- Currently on ibrutinib and have failed to achieve either a complete remission after at least 12 cycles of treatment with ibrutinib or have suboptimal response (< partial response [PR]) after being on ibrutinib treatment for 6 cycles

Must not have

- Men or women of childbearing potential who are unwilling to employ adequate contraception

Major surgery =< 4 weeks prior to registration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying whether a combination of daratumumab and ibrutinib is more effective than ibrutinib alone in treating relapsed or refractory chronic lymphocytic leukemia.

Who is the study for?

This trial is for adults with chronic lymphocytic leukemia (CLL) that has returned or didn't respond to treatment. They must have been on ibrutinib previously, have measurable disease, and be in decent physical condition. Participants need normal blood counts and liver function, not be pregnant or nursing, use effective birth control, and can't have severe lung conditions or other serious health issues.

What is being tested?

The DIRECT Study is testing the combination of daratumumab (a monoclonal antibody) with ibrutinib (an enzyme blocker) against CLL that's relapsed or refractory. The goal is to see if this combo works better than just using ibrutinib alone for these patients.

What are the potential side effects?

Possible side effects include immune system reactions leading to organ inflammation, infusion-related reactions from the antibodies, fatigue, digestive problems like nausea or diarrhea, low blood cell counts increasing infection risk, and potential liver abnormalities.

Eligibility Criteria

Inclusion Criteria

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

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I have CLL/SLL that has come back or didn't respond to treatment, and I've had at least one prior therapy.

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I've been on ibrutinib for at least 6 months without full remission.

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

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My condition is confirmed B-CLL as per specific medical guidelines.

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My condition worsened despite taking ibrutinib.

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My cancer can be measured by tests or scans.

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I have CLL/SLL that has come back or didn't respond to treatment, and I've had at least one prior therapy.

Exclusion Criteria

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

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I am of childbearing age and not using birth control.

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

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I am not pregnant, breastfeeding, or planning to become pregnant.

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I am currently breastfeeding.

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I have not received any treatment for my CLL.

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I haven't used any experimental drugs or therapies in the last 14 days.

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I have COPD with less than half the normal lung function.

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I have received daratumumab for cancer treatment before.

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I am currently taking warfarin or similar blood thinners.

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I need treatment with strong medication that affects liver enzymes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 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

Secondary study objectives

Incidence of adverse events

Minimal residual disease (MRD) response rate

Progression-free survival

Side effects data

From 2024 Phase 3 trial • 498 Patients • NCT02136134

44%

Thrombocytopenia

38%

Peripheral sensory neuropathy

38%

Peripheral Sensory Neuropathy

32%

Anaemia

24%

Fatigue

22%

Diarrhoea

17%

Upper respiratory tract infection

17%

Upper Respiratory Tract Infection

16%

Constipation

15%

Insomnia

15%

Asthenia

13%

Cough

11%

Nausea

11%

Neuralgia

11%

Pyrexia

11%

Dizziness

10%

Back Pain

10%

Pneumonia

10%

Back pain

10%

Neutropenia

Dyspnoea

Oedema peripheral

Oedema Peripheral

Pain in extremity

Hyperglycaemia

Pain in Extremity

Arthralgia

Headache

Paraesthesia

Bronchitis

Bone pain

Epistaxis

Bone Pain

Decreased Appetite

Hypocalcaemia

Dyspepsia

Leukopenia

Hypokalaemia

Decreased appetite

Lymphopenia

Oedema

Vomiting

Hypotension

Alanine aminotransferase increased

Abdominal pain

Nasopharyngitis

Alanine Aminotransferase Increased

Hypertension

Rash

Abdominal Pain Upper

Conjunctivitis

Hypophosphataemia

Abdominal pain upper

Influenza

Muscle Spasms

Musculoskeletal Chest Pain

Aspartate aminotransferase increased

Muscle spasms

Urinary tract infection

Myalgia

Herpes zoster

Musculoskeletal chest pain

Herpes Zoster

Pulmonary Embolism

Weight Decreased

Pulmonary embolism

Myocardial infarction

Dehydration

Myocardial Infarction

Lower Respiratory Tract Infection

Abdominal Pain

Orthostatic Hypotension

General Physical Health Deterioration

Condition aggravated

General physical health deterioration

Hyponatraemia

Orthostatic hypotension

Lower respiratory tract infection

Syncope

Productive cough

Nasal congestion

Respiratory failure

Weight decreased

Chills

Gastroenteritis

Sepsis

Respiratory Failure

Condition Aggravated

100%

80%

60%

40%

20%

Study treatment Arm

Bortezomib + Dexamethasone (Vd)

Daratumumab + Bortezomib and Dexamethasone (DVd)

Switch From Bortezomib + Dexamethasone (Vd) to Daratumumab Monotherapy

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 (daratumumab, ibrutinib)Experimental Treatment2 Interventions

Patients receive daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and then on day 1 of subsequent cycles. Beginning in cycle 2, patients also receive ibrutinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibrutinib

2014

Completed Phase 4

~2060

Daratumumab

2014

Completed Phase 3

~2000