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

Phase 2

Recruiting

• Conditions: Nodal T-follicular Helper Cell Lymphoma
• Interventions: Drug: linperlisib combined with CHOP regimen

• Registration Number: NCT06347653
• Lead Sponsor: Peking University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-13
• Study Start: 2023-11-28
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-02
• Last Update Submitted: 2024-04-02
• Study First Posted: 2024-04-04
• Last Update Posted: 2024-04-04
• Primary Completion: 2027-01-31
• Study Completion: 2030-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
linperlisib combined with CHOP regimen	linperlisib combined with CHOP regimen	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Bejing Cancer Hospital; 🇨🇳 Beijing, Beijing, China