GVM±R in Patients With Relapsed or Refractory Aggressive NHL
Study Details
Study Description
Brief Summary
This is a prospective, dose-escalation clinical study to evaluate the safety and efficacy of GVM±R in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
This is a single-arm, single-center, dose-escalation clinical study to explore the maximum tolerated dose (MTD) of liposomal mitoxantrone hydrochloride when combined with gemcitabine, vinorelbine and/or rituximab (GVM ± R) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Liposomal mitoxantrone hydrochloride will be given on day 1 at four different doses (16 mg/m2, 18 mg/m2, 20 mg/m2,22 mg/m2) and be combined with gemcitabine, vinorelbine and/or rituximab (rituximab only in CD20+ lymphoma). The dose limited toxicity (DLT) will be evaluated after the first cycle of therapy. A maximum of 6 cycles of therapy are planned.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Liposomal mitoxantrone hydrochloride 16 mg/m^2 (with a caret included)
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Drug: Liposomal Mitoxantrone Hydrochloride dose level 1
Drug: Liposomal Mitoxantrone Hydrochloride 16 mg/m^2 (with a caret included) on day 1, every 3 weeks;
Drug: Gemcitabine
Gemcitabine (800 mg/m^2) on day 1,8, every 3 weeks;
Drug: Vinorelbine
Vinorelbine (25mg/m^2) on day 1,8, every 3 weeks;
Other Names:
Drug: Rituximab
Rituximab (375mg/m^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;
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Experimental: Liposomal mitoxantrone hydrochloride 18 mg/m^2 (with a caret included)
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Drug: Liposomal Mitoxantrone Hydrochloride dose level 2
Drug: Liposomal Mitoxantrone Hydrochloride 18 mg/m^2 (with a caret included) on day 1, every 3 weeks;
Drug: Gemcitabine
Gemcitabine (800 mg/m^2) on day 1,8, every 3 weeks;
Drug: Vinorelbine
Vinorelbine (25mg/m^2) on day 1,8, every 3 weeks;
Other Names:
Drug: Rituximab
Rituximab (375mg/m^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;
|
Experimental: Liposomal mitoxantrone hydrochloride 20 mg/m^2 (with a caret included)
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Drug: Liposomal Mitoxantrone Hydrochloride dose level 3
Drug: Liposomal Mitoxantrone Hydrochloride 20 mg/m^2 (with a caret included) on day 1, every 3 weeks;
Drug: Gemcitabine
Gemcitabine (800 mg/m^2) on day 1,8, every 3 weeks;
Drug: Vinorelbine
Vinorelbine (25mg/m^2) on day 1,8, every 3 weeks;
Other Names:
Drug: Rituximab
Rituximab (375mg/m^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;
|
Experimental: Liposomal mitoxantrone hydrochloride 22 mg/m^2 (with a caret included)
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Drug: Liposomal Mitoxantrone Hydrochloride dose level 4
Drug: Liposomal Mitoxantrone Hydrochloride 22 mg/m^2 (with a caret included) on day 1, every 3 weeks;
Drug: Gemcitabine
Gemcitabine (800 mg/m^2) on day 1,8, every 3 weeks;
Drug: Vinorelbine
Vinorelbine (25mg/m^2) on day 1,8, every 3 weeks;
Other Names:
Drug: Rituximab
Rituximab (375mg/m^2) on day 1, every 3 weeks, only used in patients with CD20+ lymphoma;
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) [Through the last patient complete his DLT observation, assessed up to 21 days]
Maximum tolerated dose (MTD) of liposomal mitoxantrone hydrochloride in GVM±R
Secondary Outcome Measures
- Dose limited toxicities (DLTs) [Through the last patient complete his DLT observation, assessed up to 21 days]
adverse events (AE) defined as DLT events per protocol
- The incidence rates of AE and SAE [up to 28 days after the last patient complete his study therapy]
AE or severe adverse events (SAE) occur since the first dose of therapy is given
- Objective response rate (ORR) [up to 2 years]
Response is assessed according to the lugano criteria
- Complete response rate (CRR) [up to 2 years]
Response is assessed according to the lugano criteria
- progression-free survival(PFS) [up to 2 years]
From the date of the first dose of therapy is given until disease progression, death or last follow-up
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects fully understand and voluntarily participate in this study and sign the informed consent
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Age ≥18, ≤70years, no gender limitation
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Expected survival ≥ 3 months;
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Histologically confirmed diagnosis of aggressive NHL.
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Subjects with relapsed or refractory NHL. Relapsed disease is defined as the disease relapsing after CR or PR, and the duration of prior response is more than 6 months. Refractory disease can be confirmed if any of the following conditions are met: 1) no PR or CR has been obtained after previous treatment; 2) CR / PR was achieved after prior therapy, but recurred within 6 months; 3) Recurrence after hematopoietic stem cell transplantation.
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Subjects must have at least one evaluable or measurable lesion per lugano2014 criteria: for lymph node lesions, the length and diameter should be > 1.5cm; For non-lymph node lesions, the length and diameter should be > 1.0cm;
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Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) : 0-1
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The following baseline laboratory criteria are required: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count (PLT) ≥75×109/L, Hemoglobin(HB)≥ 80g/L, Total bilirubin (TBIL) ≤1.5X upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN, Serum creatinine (Scr) ≤1.5X ULN.
Exclusion Criteria:
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The subject had previously received any of the following anti-tumor treatments:
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Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;
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Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (1 mg doxorubicin equivalent to 2 mg epirubicin);
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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 before the first administration of the study drugs;
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Subjects who received autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation within 100 days of the first administration of study drugs;
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Hypersensitivity to any study drug or its components;
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Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.)
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Heart function and disease meet one of the following conditions:
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Long QTc syndrome or QTc interval > 480 ms;
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Complete left bundle branch block, grade II or III atrioventricular block;
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Serious and uncontrolled arrhythmias requiring drug treatment;
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New York Heart Association grade ≥ III;
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Cardiac ejection fraction (LVEF)< 50%;
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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.
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Hepatitis B and hepatitis C active infection (defined as hepatitis B virus surface antigen positive and hepatitis B virus DNA higher than 1x103 copy/mL; hepatitis C virus RNA high than 1x103 copy/mL) 10. Human immunodeficiency virus (HIV) infection (defined as HIV antibody positive) 11. 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.
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Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures; 13. Unsuitable subjects for this study determined by the investigator.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
- CSPC Ouyi Pharmaceutical Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CSPC-DED-DLBCL-K02