Phase I Trial of GB1211 (Selvigaltin), an Oral Galectin-3 (Gal-3) Inhibitor, Combined With Standard of Care Treatment in Relapsed/Refractory Multiple Myeloma (RRMM)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
This phase I trial studies the side effects and best dose of selvigaltin when given together with standard of care treatment (daratumumab-hyaluronidase, carfilzomib, dexamethasone) in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Selvigaltin works by blocking the activity of a protein called galectin-3. Galectin-3 is involved in various cellular processes, including inflammation and tissue scarring, which is associated with worse outcomes in several forms of cancer. By blocking the activity of galectin-3, selvigaltin may help reduce inflammation and tissue scarring. Daratumumab-hyaluronidase is a drug composed of daratumumab and hyaluronidase. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Hyaluronidase helps deliver the daratumumab to CD38-expressing cancer cells. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving selvigaltin with standard of care treatment may be safe, tolerable, and/or effective in treating patients with relapsed or refractory multiple myeloma.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of selvigaltin in combination with standard of care treatment regimen (daratumumab, carfilzomib, and dexamethasone) for relapsed/refractory multiple myeloma (RRMM).
II. Determine the maximal tolerated dose (MTD) of selvigaltin in combination with a standard of care treatment regimen (daratumumab, carfilzomib, and dexamethasone) for RRMM.
SECONDARY OBJECTIVES:
I. To collect safety and preliminary efficacy data. II. Rate of bone marrow measurable residual disease (MRD) negativity.
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
- •Age ≥ 18 years
- •RRMM with measurable disease prior to initiation of study intervention. Measurable disease must include at least one of the following criteria:
- •Serum M-protein > 0.5 g/dL or,
- •Urine M-protein > 200 mg/24h or,
- •Serum free light chain assay: involved free light chain (FLC) level > 100 mg/L provided serum free light chain ratio is abnormal or,
- •Bone marrow plasma cells > 10% of total bone marrow cells
- •Have received ≥ 1 prior line of therapy
- •Planned treatment with the standard of care regimen of daratumumab, carfilzomib, and dexamethasone (Dara-KD) regimen
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Absolute neutrophil count: ≥ 1,000 /µL
- •Platelets: ≥ 75,000 /µL
- •Hemoglobin: ≥ 7 g/dL
- •Total bilirubin: ≤ 1.5 x upper limit of normal (ULN): ≤ 3.0 x ULN for Gilbert's Syndrome
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): ≤ 3 x ULN
- •Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min
- •Left ventricular ejection fraction of at least 50% by ECHO or MUGA
- •Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for 6 months following the last dose of the investigational drug. 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
- •Participants must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
排除标准
- •Known hypersensitivity to selvigaltin or any of the excipients
- •Prior hypersensitivity or grade 3 skin toxicity with daratumumab/carfilzomib
- •Exposure to prior daratumumab/carfilzomib is permitted, however refractoriness within 6 months of study initiation is exclusionary
- •Concomitant medication(s) known to be (a) a strong inhibitor or inducer of CYP3A4, (b) strong P-gp/MDRI inhibitors or inducers or, (c) QT interval (QT) prolonging as defined in the drug's label, with the exception of drugs that are considered absolutely essential for the care of the subject or if the Investigator believes that beginning therapy with such medication is vital to an individual subject's care while on study, and in either case, there is no alternative medication
- •Electrocardiogram (ECG) demonstrating a corrected QT interval (QTc) interval > 470 msec without a bundle block or patients with congenital long QT syndrome
- •Coronary artery bypass, angioplasty, vascular stent, myocardial infarction, angina or congestive heart failure in the last 6 months
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, class III or IV heart failure (New York Heart Association functional classification system), or psychiatric illness/social situations that would limit compliance with study requirements
- •Known active bacillus tuberculosis infection
- •Known active HIV unless CD4+ > 350 cells/µL, no history of AIDS-defining opportunistic infection within the past 12 months, or on effect anti-retroviral therapy (ART) with > 4 weeks on treatment and viral load < 400 copies/mL. Confirm low risk of drug-drug interactions or are able to be substituted
- •Pregnant or nursing female participants
- •Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
研究组 & 干预措施
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Bone Marrow Aspiration (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Bone Marrow Biopsy (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Computed Tomography (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Echocardiography Test (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Multigated Acquisition Scan (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Questionnaire Administration (Other)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Carfilzomib (Drug)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Dexamethasone (Drug)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Daratumumab and Recombinant Human Hyaluronidase (Drug)
Treatment (selvigaltin, Dara-KD)
See Detailed Description.
干预措施: Selvigaltin (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: Up to 28 days
As assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version (v) 5.0. The DLTs will be summarized by dose level using frequencies and relative frequencies.
Maximum tolerated dose (MTD)
时间窗: Up to 28 days
Will determine the MTD of selvigaltin when administered in combination with daratumumab, carfilzomib, and dexamethasone (DaraKD). Will employ the Bayesian optimal interval design to find the MTD.
Recommended phase 2 dose (RP2D)
时间窗: Up to 28 days
Will determine the RP2D of selvigaltin when administered in combination with DaraKD. The RP2D will be determined by evaluating both the toxicity profile and the therapeutic response.
次要结局
- Incidence of overall adverse events(Up to 6 cycles (Cycle length = 28 days))
- Incidence of serious adverse events(Up to 6 cycles (Cycle length = 28 days))
- Overall response rate(During or after 6 cycles of therapy, assessed up to 3 years (Cycle length = 28 days))
- Duration of response(During or after 6 cycles of therapy, assessed up to 3 years (Cycle length = 28 days))
- Progression free survival(From the start of treatment until the first occurrence of disease progression or death from any cause, whichever comes first, assessed up to 3 years)
- Overall survival(From the start of treatment to death from any cause, assessed up to 3 years)
- Patient reported outcomes(At baseline, cycle 4 day 1, and 30 days after last dose of study drug)
- Bone marrow measurable residual disease (MRD) status(After 6 cycles (Cycle length = 28 days))