A Phase II Study of Oral JAK1/JAK2 Inhibitor INC424 in Adult Patients With Relapsed/Refractory Classical Hodgkin's Lymphoma (HIJAK)

Phase II study to assess the efficacy of 6 cycles of oral JAK1/2 inhibitor ruxolitinib in patients with advanced Hodgkin's lymphoma for whom no curative option is available.

Study Overview

• Status: Completed
• Conditions: Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 10200
    • UCL Louvain St Luc
  • Yvoir, Belgium, 5530
    • Universite Catholique de Louvain Mont Godinne
• France
  • Caen, France, 14000
    • CHU Côte de Nacre
  • Creteil, France, 94010
    • Hôpital Henri Mondor
  • Dijon, France, 21000
    • Chu Dijon
  • Lille, France, 59037
    • CHRU de Lille
  • Lyon, France, 69373
    • Centre Leon Berard
  • Lyon, France, 69495
    • Centre Hospitalier Lyon Sud
  • Nantes, France, 44093
    • CHU de Nantes, Hôtel Dieu
  • Rouen, France, 76038
    • Centre Henri Becquerel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion critera:

• Patients ≥ 18 years with classical HL relapsing or refractory after at least 1 prior systemic therapy. Patients must have relapsed after high-dose therapy with ASCT, or have been deemed ineligible for high-dose therapy with ASCT
• ECOG performance status ≤ 3
• Measurable nodal disease: 1 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan (MRI is allowed only if CT scan cannot be performed).

• Patient has the following laboratory values:

  • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L [SI units 1.0 x 10^9/L]
  • Platelet count ≥ 75 x 10^9/L]
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome)
  • AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN or ≤ 5.0 x ULN if the transaminase elevation is due to liver disease involvement
• Signed written informed consent
• Life expectancy ≥ 3 months
• Corrected QT interval ≤ 450 mSec
• Men and women of childbearing potential must agree to use an adequate method of contraception during the study treatment and for at least 1 week after the last study drug administration
• The patient must be covered by a social security system (for inclusions in France)

Exclusion criteria:

• Previous treatment with ruxolitinib or another JAK inhibitor
• Contraindication to ruxolitinib
• Patient received chemotherapy or radiotherapy or any investigational drug within 14 days prior to starting study drug or whose side effects of such therapy have not resolved to ≤ grade 1
• Patient treated with allogeneic hematopoietic stem cell transplant who is currently on, or has received immunosuppressive therapy within 90 days prior to start of screening and/or have ≥ Grade 2 graft versus host disease (GvHD).
• Patient with prior history of another active primary malignancy ≤ 2 years before study entry, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
• Any serious active disease or co-morbid medical condition that, according to the investigator's decision, will substantially increase the risk associated with the subject's participation in the study.
• Uncontrolled infectious disease, including active HBV infection defined by either detection of HBs Antigen or presence of anti HBc antibody without detectable anti HBs antibody.
• HIV, HCV or HTLV serology positivity and/or documented infection with active hepatitis B
• Prior history of CNS involvement with lymphoma
• Pregnant or lactating woman
• Adult patient unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ruxolitinib; Induction period: Ruxolitinib will be given twice daily during 6 cycles of 28 days. Maintenance period: patients who achieve at least a stable disease (according Cheson 2007) at the end of cycle 6 and for whose a clinical benefit is observed according to the Investigator's opinion will be eligible for maintenance treatment by ruxolitinib twice daily every day of 28-day cycles.

Drug: Ruxolitinib; Other Names: JAKAVI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response Rate (ORR) according to Cheson 2007	Overall Response Rate according to the International Working Group criteria (Cheson 2007) is defined as patient with Complete response or Partial response. Patient without response assessment (due to whatever reason) will be considered as non responder.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) according to Cheson 1999	Overall Response Rate according to the International Working Group criteria (Cheson 1999) is defined as patient with Complete response, unconfirmed Complete response or Partial response. Patient without response assessment (due to whatever reason) will be considered as non responder.	6 months
Complete response rates (CR) according to Cheson 2007 and 1999	Assessment of response will be based on the International Workshop to Standardize Response criteria for lymphoma: Cheson, 1999 and 2007. Patient without response assessment (due to whatever reason) will be considered as nonresponder.	2 months, 4 months and 6 months
Best Response Rate (BRR) according to Cheson 1999 and 2007	Disease response evaluation at 2; 4 and 6 months will be used to determine the Best Response Rate, according to Cheson 1999 and 2007. The Best Complete Response and Best Overall Response will be presented. Patient without response assessment (due to whatever reason) will be considered as nonresponder.	6 months
Safety endpoints	Description of all adverse events, vital signs measurements, clinical laboratory measurements and concomitant medications.	30 months
Time to response	Time to response will be defined as the time from inclusion into the study to the time of attainment of PR or CR according to Cheson 2007 criteria.	Up to 30 months
Duration of response	Duration of response will be measured from the time of attainment of CR or PR according to Cheson 2007 cirteria to the date of first documented disease progression, relapse or death from any cause. Patients alive and free of progression will be censored at their last follow-up date.	Up to 4.5 years
Progression Free Survival (PFS)	PFS is defined at the time from inclusion into the study to the first observation of documented disease progression/relapse according to Cheson 2007 criteria or death due to any cause. If a subject has not progressed or died, PFS will be censored at the time of last visit.	Up to 4.5 years
Overall Survival (OS)	OS will be measured from the date of inclusion to the date of death from any cause. Patients who did not died will be censored at the time of last visit.	Up to 4.5 years
Evaluation of systemic symptoms	Evaluation of efficacy of ruxolitinib on systemic symptoms such as fever, sweating, fatigue and itching will be done via systemic symptoms Questionnaire designed for this purpose and completed at Baseline and then at Day1 of each visit during Induction and Maintenance period of the study	Up to 30 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anatomopahtological study	FISH: JAK2 copies and rearrangements; Immunohistochemistry: JAK2 overexpression	baseline

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Collaborators: Novartis
• Investigators: Principal Investigator: Franck MORSCHHAUSER, MD, Lymphoma Study Association; Principal Investigator: Eric Van Den Neste, MD, Lymphoma Study Association

Publications and helpful links

General Publications

• Van Den Neste E, Andre M, Gastinne T, Stamatoullas A, Haioun C, Belhabri A, Reman O, Casasnovas O, Ghesquieres H, Verhoef G, Claessen MJ, Poirel HA, Copin MC, Dubois R, Vandenberghe P, Stoian IA, Cottereau AS, Bailly S, Knoops L, Morschhauser F. A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma. Haematologica. 2018 May;103(5):840-848. doi: 10.3324/haematol.2017.180554. Epub 2018 Jan 19.

Helpful Links

• LYSA (the Lymphoma Study Association)

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 12, 2018

Study Registration Dates

• First Submitted: June 11, 2013
• First Submitted That Met QC Criteria: June 11, 2013
• First Posted (Estimate): June 13, 2013

Study Record Updates

• Last Update Posted (Actual): August 22, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Multicenter, single arm and opened label phase II study
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease
• Other Study ID Numbers: HIJAK