NCT05660369招募中1 期
INCIPIENT: INtraventricular CARv3-TEAM-E T Cells for PatIENTs With GBM
Marcela V. Maus, M.D.,Ph.D.1 个研究点 分布在 1 个国家目标入组 21 人开始时间: 2023年3月22日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Number of Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The goal of this research study is to determine the best dose of CARv3-TEAM-E T Cells for treating participants with glioblastoma.
The name of the treatment intervention used in this research study is:
-CARv3-TEAM-E T Cells (or Autologous T lymphocytes).
详细描述
This is a non-randomized, open label, single site Phase 1 study to define the appropriate dose of CARv3-TEAM-E and evaluate its safety for the treatment of recurrent or newly diagnosed glioblastoma.
The U.S. Food and Drug Administration (FDA) has not approved CARv3-TEAM-E T Cells as a treatment for any disease. This is the first time that CARv3-TEAM-E T Cells will be given to humans. CARv3-TEAM-E T Cells are made from a person's own collected immune cells (T-Cells) that are genetically changed and then delivered back into the body to try to kill their cancerous cells.
The research study procedures include screening for eligibility, study treatment, including evaluations and follow up visits, blood collections, echocardiograms, and radiologic imaging of tumors.
It is expected participants will receive treatment over a period of short-term (approx. 2 years) and then long-term follow-up of up to 15 years.
It is expected that about 21 people will take part in this research study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Safety Run In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant
- •Participants must have histologically confirmed recurrent GBM or molecular features of GBM with presence of EGFRvIII mutation detected at initial diagnosis. MGMT methylated, unmethylated, or unknown is allowed.
- •Participants must be at first progression or recurrence and plan is for biopsy or surgical debulking. Participants must have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.
- •Participants must be 2 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent before proceeding with collection or treatment. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.
- •ARM 2: Newly Diagnosed GBM, EGFRvIII mutant (will only open once safety is confirmed in Arms 1 and 3)
- •Participants must have histologically confirmed newly diagnosed GBM with presence of EGFRvIII mutation and their tumors must be MGMT unmethylated.
- •Treatment planned with involved field radiation alone without concomitant or sequential temozolomide.
- •ARM 3: Recurrent GBM, EGFRvIII negative
- •Participants must have histologically confirmed recurrent GBM with EGFR amplification but no EGFRvIII mutation based on initial diagnostic tissue.
- •Participants must be at first recurrence and plan is for biopsy or surgical debulking. Participants must have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.
- •Participants must be 2 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.
- •ARM 1: Recurrent GBM, EGFRvIII mutant and ARM 3: Recurrent GBM, EGFRvIII negative:
- •Must be at least 3 months from completion of radiation or evidence of progression is outside the high dose radiation field.
- •Safety Run-In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant and ARM 3: Recurrent GBM, EGFRvIII negative:
- •Participants must have measurable disease, defined as at least one lesion ≥10 mm (≥1 cm) with MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
- •ALL ARMS:
- •Patients cannot have posterior fossa or intramedullary spine-only disease. Leptomeningeal disease is allowed anywhere in the neuroaxis. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
- •Resolution of AEs from any prior systemic anticancer therapy or radiotherapy to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy)
- •Medically able and willing to undergo placement of an Ommaya reservoir.
- •Steroid dose anticipated to be ≤ 4 mg of dexamethasone a day or equivalent at time of first CAR-v3-TEAM-E infusion.
- •Age ≥18 years
- •Karnofsky ≥60%
- •Must be able to undergo an MRI with contrast.
- •Life expectancy of greater than 3 months.
- •Participants must have adequate organ and marrow function as defined below:
- •Absolute neutrophil count ≥1,000/mcL
- •Platelets ≥80,000/mcL
- •Total bilirubin ≤ institutional upper limit of normal (ULN); For patients with Gilbert's syndrome, total bilirubin can be ≤ 3xULN.
- •AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
- •CrCl ≥ 60 mL/min
- •Participant has no prior history of malignancy, unless the subject has been free of the disease for ≥5 years with the exception of the following noninvasive malignancies:
- •Basal cell carcinoma of the skin
- •Squamous cell carcinoma of the skin
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Incidental histologic finding of prostate cancer (T1a or T1b) or prostate cancer that is curative
- •Left ventricular ejection fraction >50% as determined by TTE.
- •The effects of CARv3-TEAM-E on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CARv3-TEAM-E administration.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Intraparenchymal posterior fossa disease
- •Intramedullary spinal disease as the only site of disease.
- •Prior EGFRvIII targeted therapies.
- •Prior bevacizumab treatment.
- •Treatment with an any prior gene-therapy or gene-modified cellular therapy.
- •Patients with a VP shunt or patients needing a shunt in the immediate future are excluded from participating
- •Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids above physiologic dosing). Intermittent topical, inhaled, or intranasal corticosteroids are allowed
- •Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
- •Participants who are receiving any other investigational agents.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to CARv3-TEAM-E (ex. cetuximab).
- •Participants with uncontrolled intercurrent illness.
- •Human immunodeficiency virus (HIV)-infected participants are not eligible.
- •Participants with evidence of chronic hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection are not eligible.
- •Participants with psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CARv3-TEAM-E , breastfeeding should be discontinued if the mother is treated with CARv3-TEAM-E.
- •For Arm 2, prior to CARv3-TEAM-E Infusion, the following criteria should be confirmed in addition to the relevant criteria above:
- •Participants must have completed 75% of the planned 6 weeks of involved field radiation without temozolomide
- •Tumor location and size criteria as in 3.1.7 above.
- •Prior cancer directed therapy other than radiation is not allowed.
研究组 & 干预措施
Safety Run-In Phase
Experimental
- Participant enrollment will be staggered by 30 days for up to 3 participants.
- Participants will receive 1 infusion of CARv3-TEAM-E.
- Phase will be expanded up to 6 participants if any Dose-Limiting Toxicities DLTs occur.
- After all participants have been enrolled, there will be an evaluation made by the Data Safety Monitoring Board (DSMB) and the FDA to determine the safety of enrollment into additional arms.
干预措施: CARv3-TEAM-E T cells (Drug)
Arm 1: Recurrent Glioblastoma (GBM), EGFRvIII Positive
Experimental
- Participants will undergo a leukapheresis procedure, or collection of mononuclear T cells via peripheral blood draw.
- Rituximab will be administered 5-10 days prior to infusion.
- Lymphodepletion chemotherapy treatment will occur 5 days prior to infusion.
- CARv3-TEAM-E will be administered via Ommaya on D0
- Participants will be followed for 2 years post-treatment.
- Participants who are deriving clinical benefit and have sufficient product can be retreated with up to 5 additional doses.
干预措施: CARv3-TEAM-E T cells (Drug)
Arm 2: Newly Diagnosed GBM, EGFRvIII Positive
Experimental
- Participants will undergo a leukapheresis procedure, or collection of mononuclear T cells via peripheral blood draw.
- Rituximab will be administered 5-10 days prior to infusion.
- Lymphodepletion chemotherapy treatment will occur 5 days prior to infusion.
- CARv3-TEAM-E will be administered via Ommaya on D0
- Participants will be followed for 2 years post-treatment.
- Participants who are deriving clinical benefit and have sufficient product can be retreated with up to 5 additional doses.
干预措施: CARv3-TEAM-E T cells (Drug)
Arm 3: Recurrent GBM, EGFRvIII Negative
Experimental
- Participants will undergo a leukapheresis procedure, or collection of mononuclear T cells via peripheral blood draw.
- Rituximab will be administered 5-10 days prior to infusion.
- Lymphodepletion chemotherapy treatment will occur 5 days prior to infusion.
- CARv3-TEAM-E will be administered via Ommaya on D0
- Participants will be followed for 2 years post-treatment.
- Participants who are deriving clinical benefit and have sufficient product can be retreated with up to 5 additional doses.
干预措施: CARv3-TEAM-E T cells (Drug)
结局指标
主要结局
Number of Dose-Limiting Toxicities (DLTs)
时间窗: up to 6 months
Defined as any related toxicity experienced by run-in cohort of CTCAE v5 grade ≥ 4 Adverse Event
Incidence of Adverse Events (AEs)
时间窗: From Day 0 to 2 years post-treatment
Defined as the incidence of ≥ Grade 3-4 adverse events related to CARv3-TEAM-E.
次要结局
- Proportion of Participants with One Infusion(up to 6 months)
- Overall Response Rate(Day 0 to 2 years post-treatment)
- Overall Survival Rate(From Day 0 to 2 years post-treatment)
- Progression Free Survival (PFS)(Registration to 2 years post-treatment)
研究者
Marcela V. Maus, M.D.,Ph.D.
Sponsor Investigator
Massachusetts General Hospital
研究点 (1)
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