The Ohio State University Comprehensive Cancer Center –

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

Ibrutinib for Hairy Cell Leukemia A Brief Update of an Ongoing Trial

Jeff Jones, MD, MPH16 May 2015

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PLYN

BCR

CD79a

CD79b

SYK

BTK PLCγ

IBRUTINIB

GROWTHSURVIVAL

B-cell Receptor is the “Accelerator” of B-cells

NUCLEUS

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Kinase Inhibitor

Kinase Enzyme

KEYKinase Inhibitor

LOCKKinase Enzyme

Ibrutinib

Bruton Tyrosine Kinase(BTK)

A phase 2 study of single-agent ibrutinib for the treatment of relapsed/refractory classical and variant hairy cell leukemia

Primary ObjectiveTo determine treatment response after 32 weeks of ibrutinib therapy

Secondary Objectives To describe side effects of ibrutinib in hairy cell leukemia To describe the duration of clinical benefit To better understand how ibrutinib effects the growth of hairy cells

Centers Open to AccrualOhio State Columbus,OH (Jones) UTMDACC Houston,TX (Ravandi)

NIH/NCI Bethesda, MD (Kreitman)Karmanos Detroit, MI (Schiffer)

NCI 9268: Ibrutinib for Relapsed HCL

Confirmed diagnosis of hairy cell leukemia (HCL) or variant hairy cell leukemia (vHCL)

For HCL: ≥1 prior purine nucleoside analog-containing regimen (pentostatin, cladribine,

or Relapsed or de novo disease if medically unfit for chemotherapy treatment

For vHCL: Both previously untreated and relapsed patients are eligible

Preserved kidney and liver function, good general health Require treatment as defined by:

Hgb <11g/dL, plts <100K/mL, ANC <1,000/mL, enlarging nodes ≥2cm Enlarging spleen and/or liver Worsening disease-related symptoms, such as fatigue

NCI 9268: Which patients are eligible?

Ibrutinib po daily

Group 1: ibrutinib 420 mg dailyGroup 2: ibrutinib 840 mg daily

CHARACTERISTIC N = 13

Diagnosis

Relapsed cHCL 11

Relapsed vHCL 1

Tx-naïve vHCL 1

Gender

Male 12

Female 1

Median Age (range) 64 years (43-76)

Prior Therapy

Median Priors (range) 4 (1-11)

Nucleoside Analog 12

Rituximab 9

Splenectomy 5

Group 1 (420 mg/d): Patients

Side Effect % AffectedSevere

(Grade 3 or 4)Low Lymphocytes 37%Low Phosphate 30%Low Neutrophils (ANC) 23%Infection 20%

Mild(Grade 1 or 2)

Muscle aches 61%Headache 38%Dizziness 38%Diarrhea 38%Joint pains 30%Rash 30%Fatigue 30%

Group 1 (420 mg/d): Side Effects in >20%

*cHCL patient, MRD-negative by flow, IHC

**All patients with stable disease have experienced clinical benefit

Group 1 (420 mg/d): Treatment Response

Response Category Best Response(n = 13)

Complete Response* 1Partial Response 5Stable Disease** 6Progressive Disease 1

In general, response has improved with continued treatment

Early improvement in symptoms

Counts (especially neutropenia) improved slowly over the first 6 mos

Pe

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Time (days)

Group 1 (420 mg/d): Duration of Benefit

Median Follow-up = 14.5 months

69% remain on treatment with disease control

Patients Discontinuing:

3 progressed (1 vHCL, 2 cHCL)

1 patient choice (1 cHCL)

NCI 9268: Current Status 12 of 13 patients have been recruited for Group 2

(840 mg daily) Recruitment will stop temporarily after the next

patient is recruited and treated Investigators will then decide which dose best

balances safety and efficacy The trial will then recruit 18 more patients at the

selected dose

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