Hodgkin's Lymphoma
Conditions
Keywords
Multicenter, single arm and opened label phase II study
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.
Interventions
DRUGRuxolitinib
Sponsors
Novartis
The Lymphoma Academic Research Organisation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response Rate (ORR) according to Cheson 2007 | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) according to Cheson 1999 | 6 months | 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. |
| Complete response rates (CR) according to Cheson 2007 and 1999 | 2 months, 4 months and 6 months | 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. |
| Best Response Rate (BRR) according to Cheson 1999 and 2007 | 6 months | 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. |
| Safety endpoints | 30 months | Description of all adverse events, vital signs measurements, clinical laboratory measurements and concomitant medications. |
| Duration of response | Up to 4.5 years | 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. |
| Progression Free Survival (PFS) | Up to 4.5 years | 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. |
| Overall Survival (OS) | Up to 4.5 years | 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. |
| Evaluation of systemic symptoms | Up to 30 months | 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 |
| Time to response | Up to 30 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Anatomopahtological study | baseline | * FISH: JAK2 copies and rearrangements * Immunohistochemistry: JAK2 overexpression |
Countries
Belgium, France
Outcome results
None listed