Linperlisib-based Treatment Regimen in Newly Diagnosed Nodal T-follicular Helper Cell Lymphoma (nTFHL)

A Single Arm, Open Label, Multicenter Clinical Trial of Linperlisib Combined With CHOP Regimen Followed by Autologous Hematopoietic Stem Cell Transplantation and Linperlisib Monotherapy Maintenance for Newly Diagnosed Nodal T-follicular Helper Cell Lymphoma (nTFHL) Patients

This study is conducted to evaluate the efficacy and safety of linperlisib combined with CHOP regimen followed by autologous hematopoietic stem cell transplantation and linperlisib monotherapy maintenance for newly diagnosed nTFHL patients.

Study Overview

• Status: Recruiting
• Conditions: Nodal T-follicular Helper Cell Lymphoma
• Intervention / Treatment: Drug: linperlisib combined with CHOP regimen

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: PING WEI LIU, Master; Phone Number: 0086-13522796323; Email: dreaming2217@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Bejing Cancer Hospital
      • Contact: PING WEI LIU, master; Phone Number: 0086-13522796323

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed nTFHL classified by WHO-HAEM5, including nodal TFH cell lymphoma, angioimmunoblastic-type, nodal TFH cell lymphoma, follicular-type, Nodal TFH cell lymphoma, NOS
2. Patients planning to receive autologous hematopoietic stem cell transplantation;
3. No previous systemic treatment before enrollment.;
4. There is at least one measurable lesion: the longest diameter (LDi) of the lymph node lesion is greater than 1.5 cm, or the LDi of one extra lymph node lesion is greater than 1 cm (according to the 2014 Lugano classification);
5. Age range from 18 to 65 years old, regardless of gender;
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)≤2;
7. Expected survival time≥12 weeks;
8. Adequate bone marrow and organ functions; 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.WOCBP subjects and male subjects whose partners are WOCBP should agree to use effective contraception from the time of signing the ICF until 6 months after the last dose of study drug.

9. Adequate organ and bone marrow function without severe hematopoietic abnormalities and abnormal heart, lung, liver, kidney, thyroid function and immunodeficiencies (no blood transfusion, granulocyte colony-stimulating factor or other related medical support within 14 days prior to administration of study drug):

   1. Routine blood tests (not transfused, not on granulocyte colony-stimulating factor (G-CSF), not corrected with medication within 14 days prior to screening): hemoglobin (Hb) ≥ 90 g/L; neutrophils (ANC) ≥ 1.5 x 10 9/L; platelets (PLT) ≥ 100 x 109/L;
   2. Biochemical tests: TBIL <1.5 × upper limit of normal range (ULN); glutamate alanine aminotransferase (ALT) and glutamate aspartate aminotransferase (AST) ≤2.5 × ULN; serum creatinine (Cr) ≤1.25 × ULN or endogenous creatinine clearance ≥60 mL/min (Cockcroft-Gault formula);
   3. Coagulation (unless the subject is receiving anticoagulant therapy and coagulation parameters (PT/INR and APTT) are within the expected range for treatment with anticoagulants at screening): international normalized ratio (INR) ≤ 1.5 x ULN; activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
10. Volunteer to participate in clinical research and sign an informed consent form, willing to follow and capable of completing all trial procedures.

Exclusion Criteria:

If a patient has any of the following conditions should not be included in this study:

1. Known allergy to the active ingredients or excipients of linperlisib and CHOP regimens.
2. Patients with factors that affect oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction);

3. Medical History and comorbidity

   1. The subject had any active, known, or suspected autoimmune disease. Subjects who are in a stable state and do not require systemic immunosuppressive therapy are admitted;
   2. Known history of interstitial pneumonia;
   3. Current or previous history of other malignancies within 2 years prior to study enrollment.Radically treated basal cell carcinoma of the skin, papillary thyroid carcinoma, squamous skin carcinoma, carcinoma in situ of the breast and carcinoma in situ of the cervix, excepted
   4. Received systemic antitumor therapy, including chemotherapy, immunotherapy, and biotherapy (tumor vaccines, cytokines, or growth factors used to control cancer) within 28 days prior to study enrollment.
   5. Received autologous or allogeneic hematopoietic stem cell transplantation;
   6. Patients with active tuberculosis (TB) should be excluded.
   7. Severe acute or chronic infections requiring systemic treatment;
   8. Patients with hypertension that is not well controlled with antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg)
   9. Poor diabetes control (fasting blood glucose (FBG) > 10mmol/L);
   10. Patients with heart failure (New York Heart Association standard Class III or IV), poor coronary artery disease control or arrhythmia, or a history of myocardial infarction within the 6 months prior to screening despite receiving appropriate medication;
   11. Had clinically significant bleeding symptoms or definite bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, stool occult blood ++ or above at baseline, or vasculitis;
   12. Renal failure requiring hemodialysis or peritoneal dialysis;
   13. Urine routine indicated urinary protein ≥++, and 24-hour urinary protein quantity > 1.0 g；
   14. Patients who have had major surgery or severe trauma have had the effects of the surgery or trauma resolved for less than 28 days prior to enrollment；
   15. Complicated interstitial lung disease or history of severely impaired lung function;
   16. Patients requiring systemic therapy with corticosteroids (> 10 mg/day of prednisone or equivalent) or other immunosuppressive agents within 14 days prior to administration of study drug. Inhaled or topical steroids and adrenal hormone replacement at doses > 10 mg/day prednisone efficacy dose are allowed in the absence of active autoimmune disease;

4. Physical and laboratory findings

   1. A known history of human immunodeficiency virus (HIV) infection (i.e., HIV antibody positive).
   2. Active hepatitis [Hepatitis B: Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive and ALT above the upper limit of detection; Hepatitis C: Hepatitis C virus (HCV) ribonucleic acid (RNA) positive and ALT above the upper limit of detection]; co-infection with Hepatitis B and Hepatitis C;
5. Any medical history or disease evidence that may interfere with the study results or other conditions that investigators consider inappropriate for the study.
6. Pregnant or lactating women.

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: linperlisib combined with CHOP regimen

Drug: linperlisib combined with CHOP regimen; Induction therapy: cyclophosphamide 750 mg/m2 day1, doxorubicin 40-50 mg/m2 day1, vincristine 1.4 mg/m2 (max 2 mg) day1, prednisone 100 mg day1-5, linperlisib 80mg once a day，day1-21, repeat every 21 days, for 6 cycle. Consolidation therapy: high dose chemotherapy followed by autologous hematopoietic stem cell transplantation. Maintenance therapy: linperlisib 80 mg day1-28, up to 12 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	PFS will be calculated from the start of study drug treatment to the date of disease progression, death, or last follow-up, as appropriate.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	ORR is defined as sum of CR and PR rates, as assessed by the Investigator according to the Lugano Classification	After 6 cycles of induction therapy ，average of 4.2 month and post transplantation
CR rate	CR rate is defined as the percentage of patients showing complete response as assessed by the Investigator according to the Lugano Classification.	After 6 cycles of induction therapy ，average of 4.2 month and post transplantation
Success rate of stem cell collection	Success rate was assessed as the number of participants who achieved the target collection of CD34+cells ≥ 2×10^6/kg .	1day before performing an autologous hematopoietic stem cell transplant
overall survival (OS)	OS will be calculated from the start of study drug treatment to the date of disease death or last follow-up, as appropriate.	2 year
time to next anti-lymphoma treatment	TTNLT will be calculated from the start of study drug treatment to the date of starting next anti-lymphoma treatment	2 year
adverse events	incidence of adverse event, proportion of patients with dose adjustment of linperlisib	Toxicity will be graded according to the NCI-CTCAC version 4.0, from the first day of the first cycle of induction therapy to 30 days after the last dose of study drug.

Collaborators and Investigators

• Sponsor: Peking University
• Investigators: Study Director: PING WEI LIU, Master, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 4, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: maintenance treatment; autologous hematopoietic stem cell transplantation; nodal T-follicular helper cell lymphoma; linperlisib
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: 2023KT127

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No