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
4
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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Su
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wit
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Dis
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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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