A Phase 1b/2, Open-Label, Multicenter Study to Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 53
- 试验地点
- 62
- 主要终点
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
This is an open-label, multicentre study too Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined with Lenalidomide (LEN) in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) who have had at least one, but no more than three prior systemic regimens and who are not eligible for high dose chemotherapy (HDC) with autologous stem-cell transplantation (ASCT) at the time of study entry.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent
- •Age 18 years or older
- •Histologically confirmed diagnosis of DLBCL
- •Tumor tissue for retrospective central pathology review must be provided as an adjunct to participation in this study.
- •Patients must have:
- •relapsed and/or refractory disease
- •at least one bidimensionally measurable, PET positive disease site (transverse diameter of ≥1.5 cm and perpendicular diameter of ≥1.0 cm at baseline)
- •received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy
- •Eastern Cooperative Oncology Group 0 to 2
- •Patients not considered in the opinion of the investigator eligible to undergo intensive salvage therapy including ASCT
- •Patients must meet the following laboratory criteria at screening:
- •absolute neutrophil count ≥1.5 × 10^9/L
- •platelet count ≥90 × 10^9/L
- •total serum bilirubin ≤2.5 × ULN or ≤5 × ULN in cases of Glibert's Syndrome or liver involvement by lymphoma
- •alanine transaminase, aspartate aminotransferase and alkaline phosphatase ≤3 × ULN or <5 × ULN in cases of liver involvement
- •serum creatinine clearance ≥ 60 mL/minute
- •Patients who received previous CD19 targeted therapy (other than tafasitamab) must have CD19 positive lymphoma confirmed on a biopsy taken since completing the prior CD19 targeted therapy
- •Patients with primary refractory disease who received at least one, but no more than three previous systemic regimens (including a CD20 targeted therapy)
排除标准
- •Patients who are legally institutionalized or concurrent enrollment in another interventional clinical study
- •Patients who have:
- •other histological type of lymphoma
- •a history of "double/triple hit" genetics
- •Patients who have, within 14 days prior to Day 1 dosing:
- •not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy
- •undergone major surgery (with 4 weeks) or suffered from significant traumatic injury
- •received live vaccines (within 4 weeks).
- •required parenteral antimicrobial therapy for active, intercurrent infections
- •Patients who:
- •have not recovered sufficiently from the adverse toxic effects of prior therapies
- •were previously treated with IMiDs® (e.g. thalidomide, LEN)
- •have history of hyper sensitivity to compounds of similar biological or chemical composition to tafasitamab IMiDs® and/or the excipients contained in the study treatment formulations
- •have undergone ASCT within the period ≤ 3 months prior to signing the informed consent form.
- •have undergone previous allogenic stem cell transplantation
- •have a history of deep venous thrombosis/embolism and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
- •concurrently use other anticancer or experimental treatments
- •History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions
- •Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for >2 years prior to enrollment are eligible
- •Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible
- •Patients with:
- •positive hepatitis B and/or C serology.
- •known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV)
- •CNS lymphoma involvement
- •history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromise the patient's ability to give informed consent
- •history or evidence of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- •gastrointestinal (GI) abnormalities (issue with absorption) including the inability to take oral medication
- •history or evidence of severe hepatic impairment (total serum bilirubin > 3mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma
- •history of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical class
- •any other medical condition which, in the investigator's opinion, makes the patient unsuitable for the study
- •Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from breast feeding and donating eggs; agreement to ongoing pregnancy testing during the course of the study, and after study therapy has ended Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm
研究组 & 干预措施
Treatment (Tafasitamab + Lenalidomide)
Treatment:
Tafasitamab will be combined with lenalidomide in R/R DLBCL patients.
Dose:
Cohort 1: The dose of tafasitamab will be level 1 high dose in combination with the approved dose
Cohort 2: The dose of tafasitamab will be level 2 high dose in combination with the approved dose
Expansion Cohort: The dose of tafasitamab will be the dose that is deemed safe and tolerable as determined from cohort 1 & cohort 2
Treatment consisting of tafasitamab and lenalidomide combination will be administered until disease progression, unacceptable toxicity, or discontinuation for any other reason, whichever comes first. Lenalidomide can be given for up to 12 cycles in total, after which patients can continue with tafasitamab as monotherapy until progression or unacceptable toxicity.
干预措施: Tafasitamab (Drug)
Treatment (Tafasitamab + Lenalidomide)
Treatment:
Tafasitamab will be combined with lenalidomide in R/R DLBCL patients.
Dose:
Cohort 1: The dose of tafasitamab will be level 1 high dose in combination with the approved dose
Cohort 2: The dose of tafasitamab will be level 2 high dose in combination with the approved dose
Expansion Cohort: The dose of tafasitamab will be the dose that is deemed safe and tolerable as determined from cohort 1 & cohort 2
Treatment consisting of tafasitamab and lenalidomide combination will be administered until disease progression, unacceptable toxicity, or discontinuation for any other reason, whichever comes first. Lenalidomide can be given for up to 12 cycles in total, after which patients can continue with tafasitamab as monotherapy until progression or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
时间窗: up to approximately 2 years
An adverse event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. Therefore, an AE could be any unfavorable or unintended sign (including an abnormal laboratory finding) or symptom temporally associated with the use of study treatment. A TEAE was defined as any AE that started or worsened after the first dose of study treatment until 90 days after the last dose of the study treatment. An AE that was present prior to study drug administration but increased in severity after treatment start was also included as a TEAE.
Number of Participants With Any ≥Grade 3 TEAE
时间窗: up to approximately 2 years
The toxicity grade of TEAEs was graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) using the following definitions: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal; local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living (refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.). Grade 3: severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death related to AE.
次要结局
- Ctrough of Tafasitamab After 3 and 12 Treatment Cycles(predose on Cycle 3 Day 15; predose on Cycle 12 Day 28 (up to approximately 1 year [after twelve 28-day cycles]))
- Cmax of Tafasitamab After 3 Treatment Cycles(30 minutes after the end of tafasitamab infusion on Cycle 3 Day 15 (up to approximately 85 days [after three 28-day cycles]))
- Best Objective Response Rate (ORR) by Investigator Assessment up to Treatment Cycle 12(up to 19.8 months)
- Duration of Response (DoR) by Investigator Assessment(up to approximately 64 months (approximately 5 years))
- Progression-free Survival (PFS) by Investigator Assessment(up to approximately 64 months (approximately 5 years))
- Number of Participants Developing Anti-tafasitamab Antibodies up to Treatment Cycle 12(up to approximately 1 year (after twelve 28-day cycles))