Camrelizumab Plus R-CHOP Regimen in Untreated Primary Extranodal DLBCL (CREDIT)

Anti-PD-1 Antibody (Camrelizumab) Plus R-CHOP Regimen for the Primary Extranodal Treatment-Naive Diffuse Large B Cell Lymphoma (CREDIT): a Prospective, Multicenter, Single-Arm, Phase II Trial

To assess the efficacy and safety of camrelizumab combined with rituximab, vincristine, doxorubicin, cyclophosphamide and prednisone in the treatment of untreated primary extranodal DLBCL

Study Overview

• Status: Not yet recruiting
• Conditions: DLBCL; Primary Extranodal Lymphoma
• Intervention / Treatment: Drug: Camrelizumab

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Huiqiang Huang, professor; Phone Number: 0086-13808885154; Email: huang_sysu@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Male or female patients: 18-65 years old.

  • Newly diagnosed patients
  • Primary extranodal lymphoma, histologically-confirmed DLBCL( including but not limited to follicular lymphoma grade 3B, or transformed DLBCL, EBV(+) DLBCL, ALK(+) DLBCL, high grade lymphoma). The primary site is limited to the gastrointestinal tract, nasal cavity and breast, and central nervous system( CNS) involvement must be excluded. Gastrointestinal tract involvement of DLBCL can be included in the group after evaluation without bleeding or perforation risk.
  • ECOG physical condition score: 0-2 points for patients.
  • The patients must be with at least one evaluable or measurable lesion meeting Lugano 2014 criteria, the evaluable lesion was: 18F fluorodeoxyglucose / positron emission tomography (18FDG-PET) examination showed that the uptake of extranodal areas was increased (higher than that of liver) and pet and / or computed. The features of tomography (CT) were in accordance with lymphoma. The measurable lesions were nodal lesions with a length of > 15 mm or extranodal lesions with a length of > 10 mm, accompanied by an increase in 18-FDG uptake. It is necessary to exclude the case where there is no measurable lesion and the diffuse 18-FDG uptake increase in the liver.

  • Hematology values must be within the following limits at baseline:

    1. Absolute neutrophil count (ANC) ≥1,500 cells/μL. In case bone marrow involvement, ANC≥1,000 cells/μL.
    2. Platelets≥75,000 cells/μL. In case bone marrow involvement, platelets≥50,000 cells/μL
    3. Hemoglobin≥90 g/L

  • Biochemical values must be within the following limits at baseline:

    1. Alanine aminotransferase（ALT）≤3×upper limit of normal (ULN).
    2. Aspartate aminotransferase (AST) ≤3×ULN
    3. Total bilirubin≤1.5×ULN, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
    4. Serum creatinine ≤2×ULN or estimated Glomerular Filtration Rate ≥40/mL/min/1.73m2
  • LVEF within institutional normal limits, as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan.
  • Each subject (or their legally acceptable representative) must sigh an informed consent form (ICF) indicating that he or she understands the purpose of any procedures for the study and are willing to participate in the study.
  • Women of childbearing potential ( WOCBP) must have a negative serum (beta-human chorionic gonadotropin[β-hCG] ) or urine pregnancy test within 7 days before the first medication
  • Women of childbearing potential or men and their WOCBP partners should agree to take effective contraceptive measures from signing the ICF to 6 months after the last dose of study medication.

Exclusion Criteria:

- • Primary DLBCL arise in lymph nodes or other lymphatic tissues.

• Primary central nervous system lymphoma or secondary central nervous system involvement, known primary mediastinal lymphoma.
• A history of severe allergies or allergic reactions to humanized or murine monoclonal antibodies.
• In the past five years, patients with other malignant tumors have undergone radical treatment, except for basal cell carcinoma of skin, squamous cell carcinoma of skin, carcinoma in situ of breast and carcinoma in situ of cervix. History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome are known
• Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA titer (no more than 2500 copies/mL or 1000 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. In addition to active hepatitis B or hepatitis C infections requiring treatment, group trials can be conducted. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 2500 copies/mL or 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group.
• Patients with any active infections requiring systemic anti-infective treatment within 14 days of treatment.
• Received systemic antineoplastic therapy within 28 days before treatment, including chemotherapy, immunotherapy, biotherapy (cancer vaccine, cytokines, or growth factors that control cancer), etc..
• Received major surgery within 28 days before treatment or radiotherapy within 90 days before treatment.
• Received live vaccination (except influenza attenuated vaccine) within 28 days before treatment.
• Patients requiring long-term systemic glucocorticoid therapy or other immunosuppressive therapy (>prednisone 10mg/qd or equivalent dose of other glucocorticoid therapy). Allowing subjects to use local, ocular, intra-articular, intranasal and inhaled glucocorticoid therapy.
• Patients suffering from uncontrollable comorbid diseases, including but not limited to symptomatic congestive heart failure, uncontrollable hypertension, unstable angina, active peptic ulcer or bleeding disorders.
• Pregnant or lactating women.
• Patients with a history of interstitial lung disease or non-infectious pneumonia. Subjects who have previously had drug-induced or radioactive non-infectious pneumonia but asymptomatic are allowed to enroll.
• Any life-threatening disease, physical condition or organ dysfunction according to the researchers' judgment may endanger the safety of the subject or put the clinical research at excessive risk.

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: camrelizumab+R-CHOP; Induction therapy: camrelizumab in combination with rituximab Immunochemotherapy: rituximab, cyclophosphamide, hydroxyldaunorubicin, vincristine, prednisone Maintenance therapy: camrelizumab in patients achieved CR after immunotherapy

Drug: Camrelizumab; Induction therapy: Camrelizumab 200mg, ivd, D1, Rituximab 375mg/m2, ivd, D1 every 3 weeks up to 2 cycles Immunochemotherapy: Rituximab: 375mg/m2, ivd, D1; Cyclophosphamide: 750mg/m2, iv or ivd, D1; Hydroxyldaunorubicin: 50mg/m2, iv or ivd, D1; Vincristine: 1.4 mg/m2 , iv(max：2mg), D1; Prednisone: 60mg/m2, po, d1-5 every 3 weeks up to 6 cycles Maintenance therapy: Camrelizumab 200mg, ivd, D1 every 4 weeks up to 6 cycles; Other Names: Rituximab; Cyclophosphamide; Hydroxyldaunorubicin; Prednisone; Vincristine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
complete response rate	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective remission rate		24 weeks
Progression-free Survival	PFS was defined as time from study registration to first disease progression or death whichever occurred first, otherwise subject data were censored at time last known disease free	2 years
Overall Survival	OS was defined as time from study registration to death, and otherwise censored at time last known alive	2 years
Objective remission rate		six weeks
Duration of Response	The time from the first assessment of CR or PR to PD (progressive disease) or death from any cause	2 years
Percentage of Participants With Adverse Events (AEs)	Number of participants with adverse events occurring up to 30 days after the last administration are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0	Up to 30 days after the last cycle of per-protocol treatment and 90 days after last dose of anti-PD-1 antibody

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Huiqiang Huang, professor, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): October 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: DLBCL; PD-1; R-CHOP; camrelizumab; primary extranodal lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine
• Other Study ID Numbers: MA-DLBCL-Ⅱ-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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