Refractory or Recurrent CD30+ Hematologic Malignancies
Conditions
Brief summary
This is a Phase I dose escalation study designed to define the maximum tolerable dose(MDT), the safety profile, pharmacokinetic parameters, immunogenicity and anti-tumor activity of F0002-ADC in Chinese patients with relapsed/refractory CD30-positive hematologic malignancies.
Interventions
DRUGF0002-ADC
Every 21 days for 1 cycle, continue treatment until a maximum 16 cycles. Dose Escalating: 0.3 - 4.8 mg/kg
Sponsors
Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * With relapsed/refractory CD30+ disease that histologically confirmed by central laboratory assessment and pathology review (Priority for cHL, ALCL and MF). * Patients must have at least one site of measurable disease by conventional CT scan (defined by unidimensional lymph node lesion ≥ 15 mm or extranodal lesion ≥ 10 mm ), patients with MF, skin nodules can be measured by caliper to meet the criteria as measurable lesions, positive FDG uptake for cHL and ALCL. * Patients must have the following required baseline laboratory data: Hb≥80g/L, NEUT≥1.5×109/L, PLT≥75×109/L, TBIL≤1.5 times ULN, ALT/AST≤2.5 times ULN, Cr≤1.25 times ULN or Ccr≥45 ml/min, INR≤1.5 times ULN, APTT≤1.5 times ULN. * Patients must be at least 8 weeks apart from the previous autologous stem cell infusion therapy prior to the first dose. * Patients must be at least 4 weeks apart from previous radiotherapy, chemotherapy, biologics, immunotherapy, and/or other research-based anticancer therapy prior to the first dose (with nitrogen mustard, melphalan, and nitrosourea for at least 6 weeks). * Patients must have a life expectancy \> 3 months. * Voluntary consent form
Exclusion criteria
* Patients who have received an allogeneic stem cell transplant. * Patients who have had previous treatment with any anti-CD30 antibody. * Patients received antibody therapy 6 weeks or 5 plasma half-life before the first dose. * Patients who are receiving other anti-tumor treatments. * The toxicity of previous anti-tumor treatment has not recovered to grade 1 or below, except for grade 2 peripheral neurotoxicity and any level of alopecia. * Other primary malignant tumors have been seen in the past 3 years (except for cervical cancer in situ or non-melanoma skin cancer or prostate cancer with specific prostate specific antigen). * Participants with cardiovascular conditions specified in protocols. * NYHA classification grading of cardiac function III/IV. * Participants with brain or meningeal disease conditions specified in protocols. * Patients with poor diabetes control, * High-risk participants with a history of \> grade 2 peripheral neuropathy or any active neurologic disease. * Patients have psychiatric history. * Patients with a history of liver fibrosis or cirrhosis and clinical signs and symptoms suggesting liver fibrosis or cirrhosis. * Patients with previous interstitial pneumonia. * Patients have active systemic viral, bacterial or fungal infection 4 weeks prior to the first dose * HIV antibody positive / HBsAg positive / HCVAb positive. * Patients who are allergic to recombinant proteins, murine proteins or to the drug excipients. * Patients who are receiving a dose ≥ 20 mg/day of prednisone or glucocorticoid therapy. * Female patients who are breastfeeding or pregnant. * Patients with fertility who refuses to use contraception during the trial period and within 6 months after the end of the last dose. * Other reasons that researchers believe are inappropriate to participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD | Within 21 days after a single dose | the maximum tolerable dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve [AUC] | 1 months after last dose | pharmacokinetic parameter |
| Tmax | 1 months after last dose | pharmacokinetic parameter |
| Half-life Time [T1/2] | 1 months after last dose | pharmacokinetic parameter |
| Clearance [CL] | 1 months after last dose | pharmacokinetic parameter |
| Apparent Volume of Distribution [Vd] | 1 months after last dose | pharmacokinetic parameter |
| Maximum Plasma Concentration [Cmax] | 1 months after last dose | pharmacokinetic parameter |
| Incidence of adverse events | Till 1 month after last dose | — |
| Incidence of laboratory abnormalities | Till 1 month after last dose | — |
| ORR | Once every 2 cycles and once every 4 cycles after 4 cycles (each cycle is 21 days), till tumor progression/death /3 years | Objective response rate |
| DOR | Once every 2 cycles and once every 4 cycles after 4 cycles(each cycle is 21 days), till tumor progression/death /3 years | Duration of Response |
| PFS | Once every 2 cycles and once every 4 cycles after 4 cycles(each cycle is 21 days), till tumor progression/death /3 years | Progress Free Survival |
| Immunogenicity | 1 months after last dose | Anti-F0002-ADC Antibodies |
Countries
China
Outcome results
None listed