1. Ibrutinib for Hairy Cell Leukemia A Brief Update of an Ongoing Trial
Jeff Jones, MD, MPH
16 May 2015

3. B-cell Receptor is the “Accelerator” of B-cells
LYN
BCR
CD79a
CD79b
SYK
BTK
PLCγ
IBRUTINIB
GROWTH
SURVIVAL
NUCLEUS

4. Bruton Tyrosine Kinase
Kinase Inhibitor
Ibrutinib
Bruton Tyrosine Kinase
(BTK)
KEY
Kinase Inhibitor
LOCK
Kinase Enzyme
Kinase Enzyme

5. NCI 9268: Ibrutinib for Relapsed HCL
A phase 2 study of single-agent ibrutinib for the treatment of relapsed/refractory classical and variant hairy cell leukemia
Primary Objective
To 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 Accrual
Ohio State Columbus,OH (Jones)
UTMDACC Houston,TX (Ravandi)
NIH/NCI Bethesda, MD (Kreitman)
Karmanos Detroit, MI (Schiffer)

6. NCI 9268: Which patients are eligible?
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

7. Group 1: ibrutinib 420 mg daily Group 2: ibrutinib 840 mg daily
Ibrutinib po daily
Group 1: ibrutinib 420 mg daily
Group 2: ibrutinib 840 mg daily

8. Group 1 (420 mg/d): Patients
CHARACTERISTIC
N = 13
Diagnosis
Relapsed cHCL 11
Relapsed vHCL 1
Tx-naïve vHCL
Gender
Male 12
Female
Median Age (range)
64 years (43-76)
Prior Therapy
Median Priors (range)
4 (1-11)
Nucleoside Analog
Rituximab 9
Splenectomy 5

9. Group 1 (420 mg/d): Side Effects in >20%
% Affected
Severe
(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
Diarrhea
Joint pains
Rash
Fatigue

10. Group 1 (420 mg/d): Treatment Response
Response Category
Best Response
(n = 13)
Complete Response* 1
Partial Response 5
Stable Disease** 6
Progressive Disease
*cHCL patient, MRD-negative by flow, IHC **All patients with stable disease have experienced clinical benefit
In general, response has improved with continued treatment
Early improvement in symptoms
Counts (especially neutropenia) improved slowly over the first 6 mos

11. Group 1 (420 mg/d): Duration of Benefit
Percent Surviving with Disease Control
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)
Time (days)

12. 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