Copanlisib and Gemcitabine in Relapsed/Refractory PTCL

NCT03052933 | Completed Phase 1 DMC

• 1 other identifier: COPGEM
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

COPGEM (Copanlisib and Gemcitabine)chemotherapy regimen is proposed as the salvage treatment for relapsed or refractory peripheral T-cell or NK/T-cell lymphomas in this study protocol, which would be expected to be feasible and effective in this group of patients. Copanlisib (BAY 80-6946), a highly selective and potent class-1 PI3K inhibitor with sub-nanomolar IC50s against PI3Kα and PI3Kδ, has demonstrated activity in relapsed/refractory, aggressive NHLs, suggesting an ORR of 50% for T-cell lymphomas. Gemcitabine has demonstrated clinical antitumor activity against PTCLs including NK/T-cell lymphomas both as single-agent (ORR 30-50%) and in combination therapy, with limited extramedullary toxicities. Considering the evidence of activity for both agents against PTCLs, the investigators propose that targeted therapy with copanlisib in combination with gemcitabine will exhibit early elimination of rapidly growing tumor cells and be a rational therapeutic modality for use in relapsed or refractory PTCLs, if the overlapping toxicities can be managed.

Conditions

Mature T-Cell and NK-Cell Neoplasm

Keywords

copanlisib; gemcitabine; peripheral T-cell lymphoma; extranodal NK/T-cell lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT), Maximum tolerated dose (MTD) for phase I

  The recommended dose of the combination of copanlisib and gemcitabine in patients with mature T-cell or NK/T cell neoplasm

  4 weeks

• Objective response rate for phase II

  Primary efficacy data will be maximal change of radiological tumor lesion measurement using CT scan at baseline and every two cycles, with the evaluation of overall response rate, defined as the percentage of patients with a complete response (CR) or a partial response (PR).

  1 year

Secondary Outcomes (3)

• adverse events

  2 year

• Progression-free survival (PFS)

  2 year

• Overall survival (OS)

  2 year

Study Arms (1)

Copanlisib/gemcitabine

EXPERIMENTAL

Drug: Copanlisib; Drug: Gemcitabine

Interventions

Copanlisib DRUG

For phase I study, participants will receive copanlisib (in combination with gemcitabine) IV infusion at a dose of 45 mg or 60 mg on Days 1, 8, and 15 of each 28-day treatment cycle. During phase I study, participants will be treated at the level of 45 mg/dose (level+0), or 60 mg/dose (level+1) of copanlisib. Maximal tolerated dose will be determined by modified 3+3 design including level-1 dose de-escalation. For phase II study, copanlisib dose level, determined during phase I study, will be administered on Days 1, 8, and 15. Maximum 6 cycles of gemcitabine and copanlisib combination and subsequent copanlisib monotherapy in participants with ≥ SD to copanlisib and gemcitabine until maximum 12 cycles will be given for this study.

Copanlisib/gemcitabine

Gemcitabine DRUG

For phase I/II study, participants will receive gemcitabine (in combination with copanlisib) IV infusion at fixed dose of 1,000 mg/m2 on Days 1 and 8 of each 28-day treatment cycle until maximum 6 cycles.

Copanlisib/gemcitabine

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed relapsed or refractory PTCL or NK/T-cell lymphomas, excluding primary cutaneous T-cell lymphoma, and Sezary syndrome based on WHO classification,
• Age ≥ 19
• ECOG performance status ≤ 2
• at least one bi-dimensional measurable lesion
• Laboratory values
• Serum Cr \< 1.5 mg/dL or CrCl \> 50 mL/min
• Transaminase (AST/ALT) \< 2.5 x ULN (or \< 5 x ULN in the presence of lymphoma involvement of the liver)
• Bilirubin \< 1.5 x UNL ( or \< 3 x ULN in the presence of lymphoma involvement of the liver or Gilbert syndrome)
• PT (INR) ≤ 1.5 x ULN and aPTT ≤ 1.5 x ULN
• Lipase ≤ 1.5 x ULN
• Hematologic functions: absolute neutrophil count (ANC) ≥ 1,500/µL and platelet count ≥ 75,000/µL, hemoglobin ≥ 8 g/dL
• Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal for the institution
• Women of childbearing potential and men must agree to use adequate contraception when sexually active
• Written informed consent

You may not qualify if:

• B-cell NHL, or primary cutaneous T-cell lymphoma and Sezary syndrome
• Patients who had previous history of lymphoma involvement of the CNS.
• History of previous gemcitabine therapy
• Type I or II diabetes mellitus with HbA1c \> 8.5% at screening
• History of chronic hepatitis B; subjects positive for HBsAg will be excluded from this study. However, subjects with HBcAb will be eligible if they are negative for HBV DNA quantification
• History of chronic hepatitis C; subjects positive for HCV IgG will be eligible if they are negative for HCV-RNA quantification
• Known history of human immunodeficiency virus (HIV) infection
• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function
• Any other malignancies within the past 3 years except curatively treated basal cell carcinoma of the skin, carcinoma in situ of the uterine cervix, or papillary carcinoma of the thyroid
• Other serious illness or medical conditions
• Congestive heart failure \> NYHA class 2 (Appendix III)
• Unstable angina or new-onset angina within the last 3 months; Myocardial infarction within 6 months prior to study entry
• History of significant neurological or psychiatric disorders including dementia or seizure
• Uncontrolled hypertension despite optimal medical management (per investigator's opinion)
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of study treatment

Sponsors & Collaborators

• Chonnam National University Hospital: lead
• Bayer: collaborator
• Consortium for Improving Survival of Lymphoma: collaborator

Study Sites (1)

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, 519-809, South Korea

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell

Interventions

copanlisib; Gemcitabine

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 14, 2017
• Study Start: February 1, 2018
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: June 10, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)