GVM±R in Patients With Relapsed or Refractory Aggressive NHL.

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Single Arm, Open Label, Multi-center Study of Mitoxantrone Hydrochloride Liposome, Gemcitabine, Vinorelbine With or Without Anti-CD20 Monoclonal Antibody (GVM±R) in Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06244368
• Other study ID #: CSPC-DED-Ly-K03
• Status: Recruiting
• Phase: Phase 2
• Start date: January 17, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: February 2024
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: Wei Liu
• Phone: 022-23608461
• Email: liuwei[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective clinical study to evaluate the safety and efficacy of GVM±R in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL).

Description:

This is a single-arm, open label, multi-center clinical study to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in combination with gemcitabine, vinorelbine and/or anti-CD20 monoclonal antibody(GVM ± R) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL).Mitoxantrone hydrochloride liposome will be given on day 1 at dose of 18 mg/m2 and be combined with gemcitabine, vinorelbine and/or rituximab (Pts with CD20-positive lymphomas are evaluated by the investigator on whether to combine rituximab or choose another CD20 monoclonal antibody).Each cycle consists of 21 days. A maximum of 6 cycles of therapy are planned.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age =18, =65 years.

2. Expected survival = 3 months.

3. Subjects with aggressive NHL who have relapsed or proven refractory to at least one line of standard therapy or have achieved PR as the best response after a minimum of 4 cycles of therapy (patients with a Deauville score of 4 must have biopsy-proven residual disease). Relapse is defined as a disease response (PR/CR) to the last-line therapy with a duration of response exceeding 6 months. Refractory disease can be confirmed under any of the following conditions: 1) no partial or complete response to the last-line therapy; 2) the duration of complete or partial response to the last-line therapy is no longer than 6 months from the last dose of therapy; 3) Recurrence after hematopoietic stem cell transplantation.

4. Subjects must have at least one measurable lesion per lugano2014 criteria: for lymph node lesions, the long diameter should be > 1.5cm; For non-lymph node lesions, the long diameter should be > 1.0cm;

5. Eastern Cooperative Oncology Group (ECOG) : 0-2

6. Peripheral blood: Absolute neutrophil count (ANC) =1.5×109/L, Platelet count (PLT) =75×109/L, Hemoglobin(HB)= 80g/L.(Restriction may be relaxed in patients with bone marrow involvement, Absolute neutrophil count (ANC) =1.0×109/L, Platelet count (PLT) =50×109/L, Hemoglobin(HB)= 75g/L).

7. Liver and kidney function: Serum creatinine (Scr) =1.5X upper limit of normal (ULN).Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5X ULN, Total bilirubin (TBIL) =1.5X upper limit of normal (ULN).(If the lymphoma involves the liver, TBIL=3 X ULN.AST and ALT=5 X ULN). For Pts diagnosed with Gilbert's disease, TBIL was enrolled if it was =3 X ULN.-

Exclusion Criteria:

1. The subject had previously received any of the following anti-tumor treatments:

1. Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;

2. Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (For other anthracyclines, 1 mg doxorubicin equivalent to 2 mg epirubicin);

3. Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs within 4 weeks or 5 half-lives((whichever comes first) before the first administration of the study drugs;

4. Subjects who received autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation within 100 days before the first administration of study drugs;

5. Subjects who received chimeric antigen receptor T-cell (CAR-T) therapy.

2. Hypersensitivity to any study drug or its components.

3. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.)

4. Heart function and disease meet one of the following conditions:

1. Long QTc syndrome or QTc interval > 480 ms;

2. Complete left bundle branch block, grade II or III atrioventricular block;

3. Serious and uncontrolled arrhythmias requiring drug treatment;

4. New York Heart Association grade = III;

5. Left Ventricular Ejection Fractions (LVEF)< 50%;

6. A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.

5. Active hepatitis B and C infection (defined as hepatitis B virus surface antigen positive and hepatitis B virus DNA higher than the Upper limit of normal(ULN); Hepatitis C virus antibody positive and hepatitis C virus RNA higher than the Upper limit of normal).

6. Human immunodeficiency virus (HIV) infection (defined as HIV antibody positive).

7. Patients with other malignant tumors, except for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ or other tumors without treatment during the past 5 years.

8. Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures.

9. = Grade 3 neuritis.

10. Active central nervous system (CNS) lymphoma;

11. Unsuitable subjects for this study determined by the investigator. -

Related Conditions & MeSH terms

• Aggression
• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma

Intervention

Drug:
• GVM±R regimen
Mitoxantrone hydrochloride liposome (18 mg/m^2) on day 1; Gemcitabine (800 mg/m^2) on day 1,8; Vinorelbine (20mg/m^2) on day 1,8; Rituximab (375mg/m^2) on day 1; The regimen will be administered every 3 weeks, for a maximum of 6 cycles. The choice of CD20 monoclonal antibody will be determined by the attending physician.

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Qiu Lugui

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	Response is assessed according to the lugano criteria	up to 2 years
Secondary	Complete Response Rate (CRR)	Response is assessed according to the lugano criteria	up to 2 years
Secondary	Progression-Free-Survival (PFS)	From the date of the first dose of therapy is given until disease progression, death or last follow-up	up to 2 years
Secondary	Overall survival (OS)	From the date of inclusion to date of death, irrespective of cause	up to 2 years
Secondary	Incidence of Treatment-Emergent Adverse Events	The adverse events were evaluated by NCI-CTCAE 5.0 standard Hematologic and non-hematologic toxicity	up to 2 years