Classical Hodgkin lymphoma
Conditions
Interventions
Part1-Option B:ZG005 20 mg/kg Q3w GDC-0994 100 mg Bid (D1-D7, CnD1-D14)
Part-1-Option A:ZG005 20 mg/kg Q3w giredestrant 100 mg bid (D1 to end of treatment)
Part2-Extended research:ZG005 20 mg/kg Q3w GDC-0994 100 mg Bid (D1-D7, CnD1-D14) Or ZG005 20 mg/kg Q3w GDC-0994 100 mg Bid (D1-D7, CnD1-D14)ZG005 20 mg/kg Q3w GDC-0994 100 mg
Sponsors
The First Affiliated Hospital of Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Have fully understood this trial and voluntarily signed the informed consent form; 2. At the time of signing the ICF, the age should be at least 18 years old, and there is no gender restriction. 3. Histologically confirmed relapsed or refractory lymphoma: • Classical Hodgkin's lymphoma: The definition of relapsed/refractory must meet one of the following requirements: (1) Relapse or progression follows autologous stem cell transplantation after salvage chemotherapy; (2) For subjects who have not received autologous stem cell transplantation, it is required that the first-line chemotherapy must be a combination of systemic multi-drug chemotherapy. For refractory patients, it refers to those who have not achieved PR after a treatment course of more than or equal to 2 cycles. Or the treatment course is greater than or equal to 4 cycles without achieving complete remission (CR). If the best therapeutic effect or the cause of termination is PD, the number of treatment courses is not required. For patients with recurrence, they should have received at least one line of chemotherapy in the recent period before recurrence. • Mediastinal large B-cell lymphoma: Diagnosed as relapsed or refractory primary mediastinal large B-cell lymphoma (relapse: disease progression after achieving remission in recent treatment; refractory: failure to achieve CR or PR in recent treatment), and: Recurrence after autologous stem cell transplantation, or failure to achieve complete remission (CR) or complete remission (PR) within 60 days after autologous stem cell transplantation. The subject may have received intervention treatment for relapsed or refractory diseases after autologous stem cell transplantation. In such cases, the subject must have relapsed or been refractory after the last treatment. Subjects who do not meet the conditions for autologous hematopoietic stem cell transplantation have received at least two previous treatments and have not responded to the last line of treatment or have relapsed after the last line of treatment. For participants who received local consolidation radiotherapy after systemic treatment, local radiotherapy will not be regarded as a separate treatment option. Rituximab has been used in previous treatments. • Extranodal NK/ T-cell lymphoma: On the basis of chemotherapy based on asparaginase (radiotherapy is necessary for stage I/II), the definition of relapse and refractory: Relapse refers to the appearance of new lesions at the primary site or other sites after achieving complete remission (CR). Refractory refers to any of the following: PD occurs after 2 treatment cycles, PR is not achieved after 4 treatment cycles, or CR is still not achieved after 6 treatment cycles. Patients who have not responded to autologous stem cell transplantation, or have a recurrence or progression of the disease can be enrolled. 4. The subjects must be willing to provide the pathological examination results of previous bone marrow biopsies. They can accept the historical pathological biopsy results at the time of the most recent recurrence, but the disease did not improve before the start of the study treatment (only previous pathological diagnosis results within 3 months before enrollment in the treatment will be accepted), or be willing to undergo bone marrow puncture and bone marrow biopsy at the time of screening. And be willing to undergo bone marrow puncture and bone marrow biopsy after receiving treatment (for patients with positive ba
Exclusion criteria
Exclusion criteria: 1.Lymphoma known to involve the central nervous system; 2. Nodular lymphocyte-predominant Hodgkin's lymphoma (applicable to Hodgkin's lymphoma); 3. Aggressive NK cell leukemia (applicable to NK/ T-cell lymphoma); 4. At the initial diagnosis of NKTCL, there was severe hemophagocytic syndrome (applicable to NK/ T-cell lymphoma); 5. Those whose major blood vessels in the lungs have been invaded; 6. Within 7 days before the first administration of the study drug (and without receiving blood transfusion, EPO, G-CSF, platelet-generating factor and platelet transfusion within 14 days), meet any one or more of the following criteria: 6.1 Blood routine: Neutrophil count =2.5×ULN; Total bilirubin (TBIL) >=1.5×ULN; 6.3 Creatinine > 1.5×ULN, or creatinine clearance rate calculated according to the Cockcroft-Gault formula 1.5, or activated partial prothrombin time (APTT) >1.5×ULN. 7. Any significant clinical and laboratory abnormalities that the researchers consider to affect the safety assessment, such as: poorly controlled diabetes (fasting blood glucose > 8.9mmol/L); Peripheral neuropathy (NCI-CTC AE v5.0 standard grade 2 or above); 8. Thyroid dysfunction with clinical symptoms that cannot be controlled after treatment; 9. Previous treatment with immune checkpoint inhibitors has led to grade 3 irAE or permanent drug discontinuation, or has experienced grade 2 immune-related cardiotoxicity; 10. There is clinically uncontrollable third space effusion (such as pleural effusion and ascites that cannot be controlled by effusion drainage); 11. Patients who have received any of the following treatments: 11.1 Those who have previously received oral JAK inhibitor treatment for >=7 days; 11.2 Within 14 days prior to the first administration of the study drug or currently receiving systemic (oral or intravenous) immunomodulatory drugs or corticosteroids (prednisone >10 mg/ day or equivalent dose); 11.3 Those who have received chemotherapy, radiotherapy, immune checkpoint inhibitor therapy, antibody-drug conjugate complex therapy or other anti-tumor treatments within 4 weeks prior to the first administration of the study drug; Received nitrosamuridine or mitomycin C treatment within 6 weeks before the first administration; 11.4 Those who received tumor antigen vaccine treatment within 90 days before the first administration of the study drug; Have received any live attenuated vaccine within 4 weeks before the first administration, or plan to receive a live attenuated vaccine during the study period; 11.5 Those who have systematically used a potent CYP 3A4 inhibitor or fluconazole, etc. (Note: The above topical medications are allowed) within 2 weeks (or 5 half-lives, whichever is longer) before the first administration of the study drug, and those who need to continue using such drugs due to concomitant diseases; 11.6 Those who have undergone autologous hematopoietic stem cell transplantation within 90 days before the first administration of the study drug; 11.7 Those who have received allogeneic hematopoietic stem cell transplantation or parenchymal organ transplantation in the past; 11.8 Those who have undergone major surgical operations within 4 weeks prior to the first administration of the study drug,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) as assessed by LYRIC criteria.;Security; | — |
Secondary
| Measure | Time frame |
|---|---|
| PKCS,Pharmacokinetic ConcentrationAnalysis Set;Effectiveness endpoints;Immunogenicity evaluation index; | — |
Countries
China
Contacts
Public ContactJie Jin
The First Affiliated Hospital of Zhejiang University School of Medicine
Outcome results
None listed