NCT06100237招募中2 期
Teclistamab or Talquetamab in Combination With Daratumumab SC for High-Risk Smoldering Myeloma: A Clinical and Correlative Phase 2 Sequential Cohort Immuno-Oncology Study to REVIVE Early Myeloma
Carl Ola Landgren, MD, PhD1 个研究点 分布在 1 个国家目标入组 50 人开始时间: 2023年12月4日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Minimal Residual Disease (MRD) Negative as Measured by Flow Cytometry
研究概览
简要总结
The purpose of this study is to see whether combination treatment of Teclistamab and Daratumumab (Tel-Dara) or combination Talquetamab and Daratumumab (Tal-Dara) will delay the onset of multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed smoldering multiple myeloma (SMM) based on the IMWG Criteria10 including:
- •Serum M-protein ≥3 g/dL and/or BMPCs≥10 % (but <60%)
- •Absence of anemia: hemoglobin >10 g/dL
- •Absence of renal failure: serum creatinine <2.0 mg/dL
- •Absence of hypercalcemia: Calcium <10.5 mg/dL
- •Absence of lytic bone lesion on X-ray, CT, or positron emission tomography (PET)/CT and not more than 1 lesion on whole body MRI (NOTE: At the discretion of the Investigator, whole body CT or PET/CT may replace MRI in patients who have a contraindication or who are unable to have MRI performed.)
- •Involved/uninvolved light chain ratio <100 (unless involved light chain is ≤10 mg/dL) NOTE: Anemia, renal failure, and hypercalcemia is allowed if deemed unrelated to multiple myeloma (MM), see organ function criteria in point #5 below.
- •Patients must have measurable disease within the past 4 weeks, which is defined by any one of the following:
- •Serum monoclonal protein ≥ 0.5 g/dL
- •Urine monoclonal protein >200 mg/24 hour
- •Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal kappa/lambda serum free light chain ratio (reference: 0.26-1.65)
- •Other measurable disease as defined by the International Myeloma Working Group (IMWG).
- •Because the primary endpoint is MRD negativity based on bone marrow analysis, a patient without measurable disease in blood or urine may be enrolled and assessed for MRD negativity. NOTE: In patients who received minimal prior therapy within the allowable range per
排除标准
- •1, patients should have had documented measurable disease within 4 weeks of starting that respective therapy if currently unmeasurable.
- •Patients age ≥18 years.
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 assessed within the past 45 days. (See Appendix 17.1).
- •Patients must have adequate organ and marrow function ≤45 days as defined below:
- •Absolute neutrophil count (ANC) >1.0 K cells/μL; At the discretion of the Investigator, patients with an ANC of 0.5 K/μL-1.0 K/μL may also be enrolled if clinically appropriate (eg, patients with a baseline neutropenia that is chronic and/or ethnic neutropenia and that does not cause complications, e.g, no history of chronic infections).
- •Platelet count >75 K cells/μL
- •Hemoglobin >8 g/dL (transfusions are permissible if the cause of the anemia is other than myeloma)
- •Total bilirubin <1.5 X upper limit of normal (ULN). NOTE: Isolated total bilirubin ≥1.5 X ULN with conjugated [direct] bilirubin <1.5 X ULN is allowed for those participants with known Gilbert's syndrome.
- •Aspartate aminotransferase (AST)/ alanine transaminase (ALT) ≤2.5 X ULN
- •≥30 mL/min based on Modification of Diet in Renal Disease (MDRD) 4-variable Formula calculation (Appendix 17.2) or creatine clearance (CrCl) measured by a 24-hour urine collection. The estimated glomerular filtration rate (eGFR) may also be determined by using other widely accepted methods as clinically indicated, ie, Cockcroft-Gault method or the chronic kidney disease (CKD)-epidemiology collaboration (EPI) per institutional standards.
- •Patients must have SMM that is categorized as high-risk for progression to MM-related end- organ damage by both clinical and genomic characteristics. Patients may be categorized as high risk by the Program for Study and Treatment of Malignant Hemopathies (PETHEMA) (immunoparesis and ≥95% aberrant bone marrow plasma cells (aBMPCs) by flow) and/or Mayo Clinic78 (20/2/20) criteria and/or have clonal BMPCs ≥10% with any one or more of the following criteria4:
- •Serum M protein ≥3 g/dL
- •Immunoglobulin A (IgA) SMM
- •Immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes
- •Serum involved/uninvolved free light chain (FLC) ratio ≥8 (but <100)
- •Progressive increase in M-protein level (evolving type of SMM; increase in serum M- protein by ≥25% on 2 successive evaluations within a 6-month period)
- •Clonal bone marrow plasma cells (BMPC) 50%-59%
- •Abnormal plasma cell (PC) immunophenotype (≥95% of BMPCs are clonal) and reduction of ≥1 uninvolved immunoglobulin isotype(s)
- •Chromosomal abnormalities specifically translocation of chromosomes 4 or 14 (t(4;14)) or deletion of the short arm of chromosome 17 del(17p)) or gain of the long arm of chromosome 1 (1q gain) found in ≥5% of cells
- •Increased circulating PCs (PCs >5 x 106/L and/or >5% PCs per 100 peripheral blood mononuclear cells (PBMCs)
- •MRI with diffuse abnormalities or 1 focal lesion, AND/OR PET-CT with focal lesion with increased uptake without underlying osteolytic bone destruction.
- •A female participant of childbearing potential must have a negative serum or urine pregnancy test at screening (at or within 45 days of study enrollment) and within 72 hours of the start of study treatment (Section 4.7) and must agree to further serum or urine pregnancy tests during the study
- •A female participant must be (as defined in Appendix 17.3):
- •Not of childbearing potential, or
- •Of childbearing potential and practicing at least 1 highly effective method of contraception (see Appendix 17.3). NOTE: Participant must agree to continue the above throughout the study and for 3 months after the last dose of study treatment.
- •NOTE: If a woman becomes of childbearing potential after start of the study, the woman must comply with point (b) as described above.
- •A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment, as anti-cancer treatments may impair fertility.
- •A female participant must agree to not breastfeed during the study and for a period of 5 months after receiving the last dose of study treatment.
- •A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for a period of 3 months after receiving the last dose of study treatment. If the male participant's partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide), and the female partner of the male participant must also be practicing a highly effective method of contraception (see Appendix 17.3).
- •NOTE: If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception.
- •A male participant must agree not to donate sperm for the purpose of reproduction during the study and for period of 3 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment, as anti-cancer treatments may impair fertility.
- •Ability of the patient to understand and the willingness to sign a written informed consent document.
- •Have any condition that, in the opinion of the Investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements.
- •Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 3.3).
- •Exclusion Criteria:
- •Patients who have received prior systemic therapies for SMM/MM. One prior cycle (4-5 weeks) of therapy for SMM is allowed provided that patient undergoes a 4-week washout period prior to first dose of study treatment. Treatment with corticosteroids for other indications is permitted.
- •Patients who are receiving any other investigational agents for any reasons.
- •Patients who receive a live attenuated vaccine within 4 weeks of scheduled study treatment administration.
- •Contraindication to any concomitant medication, including those medications administered for infusion reaction, antiviral, antibacterial, anticoagulation, tumor lysis, or hydration prophylaxis given prior to therapy.
- •Patient has any of the following:
- •Human immunodeficiency virus (HIV)-positive with 1 or more of the following:
- •History of acquired immune deficiency syndrome (AIDS)-defining conditions cluster of differentiation (CD4)count <350 cells/mm3
- •Detectable viral load during screening or within 6 months prior to screening
- •Not receiving highly active anti-retroviral therapy
- •Had a change in antiretroviral therapy within 6 months of the start of screening
- •Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the Medical Monitor
- •Hepatitis B infection (ie, hepatitis B surface antigen (HBsAg) or hepatitis B virus (HBV)- DNA positive). Patients with resolved infection (ie, patients who are HBsAg negative but positive for antibodies to hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded. In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status; see Section 10.3.5.2.1 for further required assessments.
- •EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.
- •Active hepatitis C infection as measured by positive HCV-ribonucleic acid (RNA) testing.
- •Participants with a history of hepatitis C virus (HCV) antibody positivity must undergo HCV-RNA testing (Section 10.3.5.2.2). If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study.
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研究组 & 干预措施
Cohort A: Tec-Dara
Experimental
Participants will receive the recommended dosage combination treatment Tec-Dara.
干预措施: Teclistamab (Drug)
Cohort A: Tec-Dara
Experimental
Participants will receive the recommended dosage combination treatment Tec-Dara.
干预措施: Daratumumab SC (Drug)
Cohort B: Tal-Dara
Experimental
Dosing and treatment schedule for participants in this group will be determined after Cohort A is completed.
干预措施: Talquetamab (Drug)
Cohort B: Tal-Dara
Experimental
Dosing and treatment schedule for participants in this group will be determined after Cohort A is completed.
干预措施: Daratumumab SC (Drug)
结局指标
主要结局
Minimal Residual Disease (MRD) Negative as Measured by Flow Cytometry
时间窗: 12 months
MRD negative (10\^-5 sensitivity by flow cytometry) as best response by completion of 12 cycles. MRD negative result means no disease is detected after treatment. Status of MRD will be assessed using International Myeloma Working Group (IMWG) Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma, per discretion of treating physician.
次要结局
- Number of Treatment Related Adverse Events(Up to 25 months)
- Duration of MRD Negativity(Up to 7 years)
- Best Objective Responses (BoR)(Up to 24 months)
- Overall Response Rate (ORR)(Up to 24 months)
- Duration of Response (DoR)(Up to 24 months)
- Minimal Residual Disease (MRD) Negativity Rate by Next-Generation Sequencing (NGS)(Up to 24 months)
- Sustained MRD Negativity(Up to 7 years)
- Biochemical progression-free survival (bioPFS)(Up to 7 years)
- Clinical progression-free survival (clinPFS)(Up to 7 years)
- Overall Survival (OS)(Up to 7 years)
- Serum Concentrations of Teclistamab and Talquetamab(Up to 7 years)
- Pharmacokinetics of Teclistamab in multiple myeloma (MM)(Up to 7 years)
研究者
Carl Ola Landgren, MD, PhD
Professor of Medicine
University of Miami
研究点 (1)
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