A Phase 2 Study of Teclistamab in Relapsed or Refractory Waldenstrom's Macroglobulinemia
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Overall Immunoglobulin M Response in Relapsed or Refractory Participants with Waldenstrom's Macroglobulinemia
研究概览
简要总结
The goal of this clinical trial is to assess the efficacy of teclistamab in participants with relapsed or refractory Waldenstrom's macroglobulinemia who have received prior therapy. This study also aims to assess the safety and tolerability of teclistamab, how quickly and to what extent response is seen in participants, how strong any clinical benefit of teclistamab might be, and determine the response to teclistamab based on the combination of MY88 and CXCR4 mutations. The main questions it aims to answer are:
- Will teclistamab be effective in treating Waldenstrom's macroglobulinemia?
- By targeting BCMA with teclistamab, will direct Waldenstrom's macroglobulinemia tumor death occur? Participants will receive teclistamab for up to 9 cycles (cycle 1 is 14 days, cycles 2-5 are 28 days, and cycles 6-9 are 56 days) or until their disease progresses, another illness or change in their condition prevents them from further receiving the treatment, they experience unacceptable side effects, they demonstrate an inability or unwillingness to receive the medication regimen, or they decide to withdraw from the study. Participants will be followed for up to 3 years from the last treatment.
详细描述
This is an open label phase II study that will enroll 24 patients with relapsed or refractory Waldenstrom's macroglobulinemia after one or more lines of systemic therapy for WM, including an anti-CD20 monoclonal antibody-containing regimen or a BTK inhibitor. This research study is evaluating a less frequent and shorter dosing schedule of teclistamab compared to the approved dosing schedule for individuals with multiple myeloma, which includes more frequent dosing in early treatment cycles and continuing to receive teclistamab until disease progression or unacceptable side effects occur. Johnson & Johnson is supporting this research study by providing the study drug, teclistamab, and funding for the clinical trial activities. The U.S. Food and Drug Administration (FDA) has not approved teclistamab for relapsed or refractory Waldenstrom's macroglobulinemia, but it has been approved to treat other types of multiple myeloma that has come back or been difficult to treat. Teclistamab is a type of antibody-based medication that attaches to both cancer cells and the body's T cells (a type of immune cell). By connecting the two, teclistamab bring T cells close enough to the cancer cells so they can activate and kill the cancer cells directly, without needing usual immune-system signals.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinicopathological diagnosis of WM per IWWM2 criteria.
- •Meeting criteria for treatment per IWWM2 criteria.
- •Relapsed or refractory WM with at least 1 prior line of treatment, including an anti-CD20 monoclonal antibody containing regimen or a BTK inhibitor.
- •Patients should have received a prior BTK inhibitor (except for contraindications such as bulky disease, amyloidosis, significant medication interactions, or a history of severe bleeding).
- •Participants with suspected or symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred vision) must undergo plasmapheresis prior to treatment initiation.
- •Adults aged ≥18
- •ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
- •A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and again either a serum or urine pregnancy test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
- •A female participant must be:
- •Not of childbearing potential, or
- •Of childbearing potential and practicing at least 1 highly effective method of contraception
- •A male participant must wear a condom (with or without spermicidal foam/gel/film/ cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment.
- •Participants must meet the following organ and marrow function as defined below:
- •Absolute neutrophil count ≥500/mcL; the patient may enroll below this threshold if neutropenia is believed to be caused by WM bone marrow involvement. Growth factors are not permitted <14 days prior to C1D
- •Platelets ≥30,000/mcL believed to be caused by WM bone marrow involvement. Platelet transfusions are not permitted <14 days prior to C1D
- •Hemoglobin ≥ 8 g/dL. RBC transfusions are not permitted <14 days prior to C1D
- •Total bilirubin ≤ 1.5 X institutional ULN, or ≤3 x institutional ULN with documented liver metastases and/or Gilbert's Disease
- •AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- •Creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula
- •Ability to adhere to the study visit schedule and other protocol requirements.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Received any prior BCMA-directed therapy.
- •Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form.
- •Participants who are receiving any other investigational agents for this condition.
- •Participants with known CNS lymphoma.
- •Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeed while enrolled in this study.
- •History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection.
- •Patients with a history of HIV infection that is well controlled on antiretroviral therapy are eligible if all of the following criteria are met: (1) undetectable HIV viral load by standard clinical assay AND (2) CD4+ T cell count of >/=200 cells/microliter).
- •Participants with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable, and if the participant is willing to take appropriate anti-viral prophylaxis as indicated and HBV DNA monitoring on study.
- •Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- •Note: Participants with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and anti- HBs+ and anti-HBC-) and positive anti-HBc from IVIG may participate.
- •Significant cardiovascular disease defined as:
- •Unstable angina within the past 6 months, or
- •History of myocardial infarction within the past 6 months
- •Any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or
- •Uncontrolled or symptomatic arrhythmias
- •Concurrent systemic immunosuppressant therapy. Systemic steroids at doses <20mg prednisone per day are permitted.
- •Concurrent systemic anti-Waldenstrom therapy.
- •Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
- •Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- •Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
- •Major surgery within 4 weeks of first dose of study drug.
- •Participants with a known hypersensitivity to any of the excipients of Teclistamab.
- •Participants with a history of non-compliance to medical regimens, which will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
- •History of a non-lymphoma malignancy, except adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated stage 1 or 2 cancer currently in complete remission, or any other cancer that is in a complete remission.
- •Ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures.
研究组 & 干预措施
Teclistamab
Participants with relapsed or refractory Waldenstrom's macroglobulinemia will receive teclistamab. Teclistamab will be administered at the pre-determined dose on days 1, 4, and 7 of the first 14-day cycle via subcutaneous injection into their abdomen. Then, participants will be given teclistamab once every week for up to four 28-day cycles, and then for up to four 56-day cycles, with a maximum of 9 cycles.
干预措施: Teclistamab (Drug)
结局指标
主要结局
Overall Immunoglobulin M Response in Relapsed or Refractory Participants with Waldenstrom's Macroglobulinemia
时间窗: Day 1 of cycle 1 to first documentation of ORR, PR or better up to 3 years from the last treatment date.
Overall immunoglobulin M (IgM) efficacy will be evaluated by assessing the IgM response rate and the objective response rate (ORR, PR or better; at least 25% improvement in IgM from baseline). Overall response rate (ORR) includes patients who achieved minor response (MR), partial response (PR), very good partial response (VGPR), and complete response (CR). Response rates will be presented with exact 95% confidence intervals. With 24 patients, there is 99% power to reject a null rate of IgM response of 0.30 assuming an alternative IgM response rate of 0.70 based on the exact binomial exact test with a one-sided significance level of 0.03. The alternative IgM response rate will be rejected if at least 12 of 24 patients have a response.
Overall Immunoglobulin M Response in Relapsed or Refractory Participants with Waldenstrom's Macroglobulinemia
时间窗: Day 1 of cycle 1 (cycle 1 is 14 days) to first documentation of ORR, PR or better up to 3 years from the last treatment date.
Overall immunoglobulin M (IgM) efficacy will be evaluated by assessing the IgM response rate and the objective response rate (ORR, PR or better; at least 25% improvement in IgM from baseline). Overall response rate (ORR) includes patients who achieved minor response (MR), partial response (PR), very good partial response (VGPR), and complete response (CR). Response rates will be presented with exact 95% confidence intervals. With 24 patients, there is 99% power to reject a null rate of IgM response of 0.30 assuming an alternative IgM response rate of 0.70 based on the exact binomial exact test with a one-sided significance level of 0.03. The alternative IgM response rate will be rejected if at least 12 of 24 patients have a response.
次要结局
- Safety and Tolerability of Teclistamab(Day 1 of cycle 1 to end of follow-up phase, up to 3 years from the last treatment date.)
- Immunoglobulin M Major Response Rate(Day 1 of cycle 1 to first documentation of PR, VDPR, and/or CR up to 3 years from the last treatment date.)
- Median Time to Response(Day 1 of cycle 1 to first documentation of any response up to 3 years after last treatment date.)
- Median Time to Major Response(Day 1 of cycle 1 to first documentation of major response up to 3 years from last treatment date.)
- Progression-Free Survival(Day 1 of cycle 1 to first documentation of disease progression, initiation of new therapy, or death, whichever occurs first, up to 3 years from the last treatment date.)
- Overall Survival(Day 1 of cycle 1 to death or last follow-up, whichever occurs first, up to 3 years from last treatment date.)
- Overall Response Rate by Mutational Status(Day 1 of cycle 1 to first documentation of MR, PR, VGPR, and/or CR up to 3 years from last treatment date.)
- Safety and Tolerability of Teclistamab(Day 1 of cycle 1 (cycle 1 is 14 days) to end of follow-up phase, up to 3 years from the last treatment date.)
- Immunoglobulin M Major Response Rate(Day 1 of cycle 1 (cycle 1 is 14 days) to first documentation of PR, VDPR, and/or CR up to 3 years from the last treatment date.)
- Median Time to Response(Day 1 of cycle 1 (cycle 1 is 14 days) to first documentation of any response up to 3 years after last treatment date.)
- Median Time to Major Response(Day 1 of cycle 1 (cycle 1 is 14 days) to first documentation of major response up to 3 years from last treatment date.)
- Progression-Free Survival(Day 1 of cycle 1 (cycle 1 is 14 days) to first documentation of disease progression, initiation of new therapy, or death, whichever occurs first, up to 3 years from the last treatment date.)
- Overall Survival(Day 1 of cycle 1 (cycle 1 is 14 days) to death or last follow-up, whichever occurs first, up to 3 years from last treatment date.)
- Overall Response Rate by Mutational Status(Day 1 of cycle 1 (cycle 1 is 14 days) to first documentation of MR, PR, VGPR, and/or CR up to 3 years from last treatment date.)
研究者
Andrew R. Branagan, M.D., Ph.D.
Principal Investigator
Massachusetts General Hospital