Clinical trial NCT01877005: A Phase II Study of Oral JAK1/JAK2 Inhibitor INC424 in Adult Patients With Relapsed/Refractory Classical Hodgkin's Lymphoma
Official title: A Phase II Study of Oral JAK1/JAK2 Inhibitor INC424 in Adult Patients With Relapsed/Refractory Classical Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin's Lymphoma
Keywords: Multicenter, single arm and opened label phase II study
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2013-06-13
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response Rate (ORR) according to Cheson 2007
timeFrame: 6 months
Secondary outcomes:
measure: Overall response rate (ORR) according to Cheson 1999
timeFrame: 6 months
measure: Complete response rates (CR) according to Cheson 2007 and 1999
timeFrame: 2 months, 4 months and 6 months
measure: Best Response Rate (BRR) according to Cheson 1999 and 2007
timeFrame: 6 months
measure: Safety endpoints
timeFrame: 30 months
measure: Time to response
timeFrame: Up to 30 months
measure: Duration of response
timeFrame: Up to 4.5 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 4.5 years
measure: Overall Survival (OS)
timeFrame: Up to 4.5 years
measure: Evaluation of systemic symptoms
timeFrame: Up to 30 months
Other outcomes:
measure: Anatomopahtological study
timeFrame: baseline
Locations:
city: Brussels
country: Belgium
facility: UCL Louvain St Luc
city: Yvoir
country: Belgium
facility: Université Catholique de Louvain Mont Godinne
city: Caen
country: France
facility: Chu Cote de Nacre
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: Chu Dijon
city: Lille
country: France
facility: Chru de Lille
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Nantes
country: France
facility: CHU de Nantes, Hotel Dieu
city: Rouen
country: France
facility: Centre Henri Becquerel
Study officials:
affiliation: Lymphoma Study Association
name: Eric Van Den Neste, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lymphoma Study Association
name: Franck Morschhauser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.