Clinical trial NCT05238064: Parsaclisib in Combination With CHOP in Participants With Previously Untreated PTCL
Official title: PI3Kδ Inhibitor Parsaclisib in Combination With Cyclophosphamide, Doxorubicin, Vincristine and Prednisone in Participants With Previously Untreated Peripheral T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: PI3Kδ Inhibitor
Parsaclisib
CHOP
PTCL
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2022-02-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is to investigate the safety, tolerability and efficacy of PI3Kδ inhibitor Parsaclisib in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in frontline treatment of patients with peripheral T-cell lymphoma (PTCL).

Detailed description: The study is to investigate the safety, tolerability and efficacy of PI3Kδ inhibitor Parsaclisib in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in frontline treatment of patients with peripheral T-cell lymphoma (PTCL) by conducting in two stages, dose-escalation stage and dose-expansion stage. In dose-escalation stage, patients with treated-naïve PTCL will be assigned to receive sequentially higher doses of parsaclisib range from 10 to 20mg po, qd plus CHOP (21 days per cycle). The dose escalation will follow the classic 3+3 design. The recommended phase 2 dose (RP2D) of parsaclisib will be determined according to the dose-escalation results. In dose-expansion stage, additional patients will be recruited to receive Par-CHOP for the planned 6 cycles or until disease progression, unacceptable drug-related adverse events or starting new anti-lymphoma treatments.

Eligibility criteria: Inclusion Criteria:

* 1. Subjects fully understand and voluntarily participate in this study and sign informed consent
* 2. Age≥18, ≤70 years
* 3. Histologically confirmed diagnosis of treatment-naïve PTCL, including peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALCL, ALK+ALCL with IPI≥2, no limitation with ALC-ALCL), angioimmunoblastic T-cell lymphoma (AITL), enteropathy related T-cell lymphoma, hepatosplenic T-cell, γ/δ T-cell lymphoma; Other PTCL that investigators consider to be appropriate to be enrolled.
* 4. No previous systemic treatment before enrollment.
* 5. At least one measurable lesions according to LUGANO 2014 criteria.
* 6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
* 7. Life expectancy ≥3 months.
* 8. Ineligible or decline to receive autologous stem cell transplantation (ASCT).
* 9. Adequate main organ function defined as the following required baseline laboratory data: Absolute neutrophil count (ANC)≥1.5×109/L without given G-CSF within 14 days; Platelet count (PLT)≥75×109/L without given transfusion with 14 days; Hemoglobin (HB)≥8g/dL without given transfusion or erythropoietin; Total bilirubin (TBIL)≤1.5X upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5X ULN; Serum creatinine (Scr)≤1.5X ULN; Left ventricular ejection fraction (LVEF)≥50%; For female participants of childbearing period, a negative urine or serum pregnancy test should be performed with 1 week prior to receiving first dose of investigational drug (day 1 of cycle 1). If a urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Women of non-reproductive age was defined as at least 1 year after menopause or having undergone surgical sterilization or hysterectomy.
* 10.If there is a risk of pregnancy, all participants (both men and women) are required to use a contraceptive with an annual failure rate of less than 1% for entire treatment period up to 120 days after the last dose of investigational drug (or 180 days after chemotherapeutic drug).

Exclusion Criteria:

* 1. Current or previous history of other malignancies within 5 years prior to study enrollment.
* 2. Current diagnosis of any of the following: Adult T-cell leukemia/lymphoma, precursor cell lymphoblastic leukemia/lymphoma, extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), indolent cutaneous T-cell lymphoma (CTCL).
* 3. Target lesions were treated with radiotherapy within 4 weeks of enrollment.
* 4. Patients undergo interventional clinical trials.
* 5. Concurrent lymphoma with CNS invasion.
* 6. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
* 7. Known allergy to the active ingredients or excipients of IBI376 and CHOP regimens.
* 8. A known history of human immunodeficiency virus (HIV) infection (i.e., HIV antibody positive).
* 9. Positive test results for HBsAg antigen and HBV-DNA, or hepatitis C virus (HCV) antibody.
* 10. Received live vaccine within 30 days prior to initial investigational drug administration (day 1 of cycle 1) (Note: inactivated virus vaccine for injection is allowed within 30 days prior to initial administration, but live attenuated vaccine is not allowed).
* 11. Pregnant or breastfeeding women.
* 12. Any serious uncontrolled systemic disease.
* 13. Any medical history or disease evidence that may interfere with the study results or other conditions that investigators consider inappropriate for the study.

Primary outcomes:
measure: 3-year EFS
timeFrame: From date of patients sign informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Secondary outcomes:
measure: Hematology and non hematology toxicity
timeFrame: Throughout the treatment period，up to 6 months
measure: CRR
timeFrame: at the end of Cycle 6 (each cycle is 21 days)
measure: ORR
timeFrame: at the end of Cycle 6 (each cycle is 21 days)
measure: EFS
timeFrame: From date of randomization until the date of first documented event, such as progression of the disease or the occurrence of death for any reason, or receive other anti-tumor treatment, whichever came first, assessed up to 3 years
measure: OS
timeFrame: From date of patients sign informed consent until the date of death or the date of last follow-up time, whichever came first, assessed up to 3 years
Other outcomes:
Locations:
Study officials:
affiliation: Fudan University
name: Junning Cao
role: PRINCIPAL_INVESTIGATOR
References: