Clinical trial NCT01393106: Safety and Efficacy of Idelalisib in Relapsed or Refractory Hodgkin Lymphoma
Official title: A Phase 2 Study to Assess the Efficacy and Safety of GS-1101 (CAL-101) in Patients With Relapsed or Refractory Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: HL
idelalisib
CAL-101
GS-1101
PI3K
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-07-13
Enrollment: 25
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of idelalisib in participants with relapsed of refractory Hodgkin Lymphoma (HL). The primary objective will be to assess the overall response rate.

Eligible participants will initiate oral therapy with idelalisib at a starting dose of 150 mg twice daily. Treatment with idelalisib will continue until tumor progression or unacceptable toxicity.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 12 years
* Karnofsky performance score of ≥ 60 (Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2)
* Histologically confirmed diagnosis of classic HL (ie, nodular sclerosis, mixed cellularity, lymphocyte depleted, and or lymphocyte rich types)
* Nodal HL that shows fluorodeoxyglucose (FDG) avidity (defined as focal or diffuse FDG uptake above background in a location incompatible with normal anatomy or physiology), and is measurable (defined as the presence of ≥ 1 nodal lesion that measures ≥ 2 cm in a single dimension as assessed by CT, PET/CT, or magnetic resonance imaging (MRI))
* Relapsed or refractory HL after prior myeloablative therapy with autologous stem cell transplantation (ASCT) or after ≥ 2 prior chemotherapy-containing regimens and no curative option with conventional therapy
* Discontinuation of all radiotherapy or chemotherapy for the treatment of HL greater than or equal to 3 weeks before initiation of study treatment and discontinuation of all radioimmunotherapy for HL (Visit 2)
* All acute toxic effects (excluding alopecia, neurotoxicity, or anemia) of any prior antitumor therapy resolved to Grade ≤ 2 before initiation of study treatment (Visit 2)
* For men and women of childbearing potential willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods
* Willingness and ability to provide written informed consent and to comply with protocol requirements

Exclusion Criteria:

* Known active central nervous system or leptomeningeal lymphoma
* History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years
* Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment (Visit 2)
* Pregnancy or breastfeeding
* Ongoing alcohol or drug addiction
* Known history of drug-induced liver injury, chronic active hepatitis C virus (HCV), chronic active hepatitis B virus (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension
* History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
* Ongoing immunosuppressive therapy, including systemic corticosteroids.
* Prior therapy with idelalisib
* Exposure to another investigational drug within 3 weeks prior to start of study treatment
* Concurrent participation in another therapeutic treatment trial
* Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of the study drug; or impair the assessment of study results
* Prior therapy with any drug that inhibits Akt, Bruton tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTOR), phosphatidylinositol 3 kinase (PI3K) (including idelalisib), or spleen tyrosine kinase (SYK)

Primary outcomes:
measure: Overall Response Rate
timeFrame: Up to Week 110
Secondary outcomes:
measure: Duration of Response
timeFrame: Up to Week 110
measure: Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of Target Lymph Nodes as Documented Radiographically
timeFrame: Baseline, Week 8, Week 48, and up to Week 110
measure: Change From Baseline in Fluorodeoxyglucose (FDG) Uptake in Lymph Nodes as Assessed by Positron-emission Tomography (PET)
timeFrame: Up to Week 110
measure: Time to Response
timeFrame: Up to Week 110
measure: Overall Survival
timeFrame: Up to Week 110
measure: Progression Free Survival
timeFrame: Up to Week 110
measure: Time to Treatment Failure
timeFrame: Up to Week 110
measure: Changes in Health-related Quality of Life as Reported Using the Functional Assessment of Cancer Therapy: Lymphoma (FACT-Lym) Questionnaire
timeFrame: Baseline and up to Week 110
measure: Changes in Performance Status as Documented Using the Karnofsky Performance Criteria for Participants ≥ 16 Years of Age and the Lansky Performance Criteria for Participants < 16 Years of Age
timeFrame: Baseline and up to Week 110
measure: Changes in the Plasma Concentrations of Disease-associated Chemokines and Cytokines
timeFrame: Up to Week 110
measure: Overall Safety Profile of Idelalisib
timeFrame: Up to Week 110
measure: Compliance With Study Drug Dosing as Assessed by Accounting for Used and Unused Drug
timeFrame: Up to Week 110
measure: Idelalisib Trough and Peak Plasma Concentration at Week 4
timeFrame: Predose and 1.5 hours postdose at Week 4
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Lyndah Dreiling, MD
role: STUDY_DIRECTOR
References:
citation: Gopal AK, Fanale MA, Moskowitz CH, Shustov AR, Mitra S, Ye W, Younes A, Moskowitz AJ. Phase II study of idelalisib, a selective inhibitor of PI3Kdelta, for relapsed/refractory classical Hodgkin lymphoma. Ann Oncol. 2017 May 1;28(5):1057-1063. doi: 10.1093/annonc/mdx028.