Clinical trial NCT05441761: Mitoxantrone Hydrochloride Liposomes in Combination With GDP in Relapsed/Refractory PTCL
Official title: Phase I/II Clinical Study of Mitoxantrone Hydrochloride Liposomes in Combination With Gemcitabine, Dexamethasone, and Cisplatin in Relapsed/Refractory Peripheral T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Treatment
Peripheral T-cell Lymphoma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: CSPC Ouyi Pharmaceutical Co., Ltd.
First posted: 2022-07-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, open-label, single arm, multicenter clinical study to evaluate the safety, tolerability, efficacy mitoxantrone hydrochloride liposome in combination with gemcitabine, dexamethasone, and cisplatin in relapsed/refractory peripheral T-cell lymphoma

Detailed description: This is a prospective, open-label, single arm, multicenter clinical study to explore the maximum tolerated dose (MTD) of liposomal mitoxantrone hydrochloride when combined with gemcitabine, dexamethasone, and cisplatin in patients with relapsed or refractory peripheral T-cell lymphoma. Liposomal mitoxantrone hydrochloride will be given on day 1 at three different doses (12 mg/m2，16 mg/m2, 20 mg/m2) and be combined with gemcitabine, dexamethasone, and cisplatin. The dose limited toxicity (DLT) will be evaluated after the first cycle of therapy. A maximum of 6 cycles of therapy are planned. An dose expansion study of mitoxantrone hydrochloride liposome at RP2D dose level combined with gemcitabine, dexamethasone, and cisplatin was conducted to explore the efficacy and safety tolerance of the combined regimen.

Eligibility criteria: Inclusion Criteria:

1. Subjects fully understand and voluntarily participate in this study and sign informed consent
2. Age ≥18, ≤75 years, no gender limitation
3. Expected survival ≥ 3 months;
4. Histologically confirmed diagnosis of peripheral T-cell lymphoma, is one of the following subtypes (1) Peripheral T-cell lymphoma non-specific type (PTCL-NOS) (2) Angioimmunoblastic T-cell lymphoma (AITL) (3) Anaplastic large cell lymphoma (ALCL), ALK+ (4) Anaplastic large cell lymphoma (ALCL), ALK- (5) Other subtypes of PTCL that the researcher considered to be included in the group;
5. The criteria for relapsed/refractory lymphoma: Relapsed lymphoma is defined as lymphoma that relapsed after a complete response (CR) was achieved with initial chemotherapy. Refractory lymphoma is diagnosed by meeting any of the following criteria: 1) tumor reduction \< 50% or disease progression after 4 cycles of standard regimens of chemotherapy; 2) CR was achieved by standard chemotherapy, but relapse occurred within six months; 3) Two or more times of recurrence after CR; 4) Relapse after hematopoietic stem cell transplantation;
6. There must be at least one evaluable or measurable lesion meeting 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;
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2；
8. Bone marrow function: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count (PLT) ≥75×109/L, Hemoglobin(HB)≥ 80g/L(Bone marrow invasive patient ANC≥1.0×109/L,PLT≥50×109/L,HB≥75 g/L)
9. Liver and kidney function：Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) , The liver invasion≤3.0×ULN）;Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN , The liver invasion≤5.0×ULN; Serum creatinine (Scr) ≤1.5× ULN

Exclusion Criteria:

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

   1. Those who have previously received mitoxantrone or mitoxantrone liposomes;
   2. Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin is more than 550 mg/m2 (1 mg doxorubicin converted from other anthracycline drugs is equivalent to 2 mg epirubicin);
   3. Have received anti-tumor treatment (including chemotherapy, targeted therapy, hormone therapy, taking traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks before the first use of the study drugs;
   4. Patients who have received autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation within 100 days of the first medication;
2. Hypersensitivity to any study drug or its components;
3. Non controlled systemic diseases (such as active infection, non controlled hypertension, diabetes, etc.)
4. Heart function and disease meet one of the following conditions:

   1. Long QT c 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. Cardiac ejection fraction (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.
   7. Baseline NT-proBNP is greater than 800pg/ mL, cTnI is greater than the normal upper limit of our center, and the retest in three days which is still higher than the above range.
5. Hepatitis B, Hepatitis C infection in active stage (if there is a positive hepatitis B surface antigen or core antibody, additional test HBV DNA, Hepatitis B virus DNA more than 1x103 copies /mL excluded; If HCV anti-body is positive, add test for HCV RNA, and exclude HCV RNA over 1x103 copies /mL)
6. Past or current co-occurrence of other malignancies (except effectively controlled non-melanoma cutaneous basal cell carcinoma, breast/cervical carcinoma in situ, and other malignancies effectively controlled without treatment within the past five years)
7. Have primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment;
8. Pregnant and lactating women and patients of childbearing age who do not want to use contraception;
9. Conditions that other researchers deem inappropriate to participate in this study.

Primary outcomes:
measure: Recommended Phase II Dose（RP2D）
timeFrame: 1 year
measure: Objective response rate (ORR)
timeFrame: 3 year
Secondary outcomes:
measure: Dose limited toxicities (DLTs)
timeFrame: 1 year
measure: maximum-tolerated dose(MTD)
timeFrame: 1 year
measure: The incidence of AE and SAE
timeFrame: 3 year
measure: Complete response rate (CRR)
timeFrame: 3 year
measure: Duration of Response（DOR）
timeFrame: 3 year
measure: progression-free survival（PFS）
timeFrame: 3 year
measure: Overall survival（OS)
timeFrame: 3 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Luhe Hospital, Capital Medical University
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Peking University First Hospital
Study officials:
References: