NCT04682405已完成2 期
A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation (Auto-HCT) for Multiple Myeloma (MM)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Change in Diarrhea as Assessed Per CTCAE v5.0
研究概览
简要总结
The investigators hypothesize that prophylactic E-selectin inhibition via administration of uproleselan during melphalan conditioning will reduce the gastrointestinal (GI) toxicity in multiple myeloma (MM) patients undergoing auto-transplant, as assessed via diarrhea severity scoring per CTCAE v5.0, while potentially increasing chemosensitivity of malignant MM cells to high-dose melphalan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Biopsy-confirmed multiple myeloma (MM) (per IMWG criteria).
- •Undergoing first auto-HCT for MM in first partial response (PR) or better
- •Conditioning regimen to be single agent melphalan (200 mg/m^2)
- •Adults 18 to 75 years of age, inclusive
- •ECOG performance status ≤ 2
- •Mobilized ≥ 5.0 x 10^6 CD34+ cells/kg (i.e. sufficient CD34+ HSCs for one auto-HCT, with at least one back-up graft in reserve)
- •Adequate bone marrow and organ function prior to stem cell mobilization as defined below:
- •Leukocytes, absolute neutrophil count, and platelets within institutional standard limits for high-dose melphalan autologous stem cell transplant
- •Total bilirubin ≤ 1.5 x ULN (unless the patient has a history of Gilbert's Syndrome, in which case, total bilirubin must be ≤ 2.5 times the ULN)
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x ULN
- •Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
- •Baseline pulmonary function test (PFT) with carbon monoxide diffusion capacity in the lung (DLCO) ≥ 50% and forced expiratory volume in 1 second (FEV1) both within institutional standard limits for high-dose melphalan autologous stem cell transplant
- •The effects of uproleselan (GMI-1271) on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, prior sterilization procedure, abstinence, etc.) prior to study entry, for the duration of study participation and for 12 weeks after the completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Should a man who is participating in the study become aware that he has impregnated a partner, he must inform his treating physician immediately.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
- •Active signs or symptoms of CNS involvement by malignancy (lumbar puncture not required). Prior history of CNS involvement is acceptable, if patient has completed treatment for CNS involvement with documented treatment response.
- •Prior exposure to uproleselan (GMI-1271)
- •Currently receiving any other investigational agents
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to uproleselan or melphalan
- •Known active infection with hepatitis A, B (e.g., HBsAg positive), or C (e.g., anti-HCV positive), or human immunodeficiency virus
- •Uncontrolled acute life-threatening bacterial, viral, or fungal infection-Myocardial infarction within 6 months of uproleselan/placebo dosing, or subject has current significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hemodynamic instability, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- •Any medical, psychiatric, or other condition which, in the opinion of the investigator, unfavorably alters the risk-benefit of subject participation, is likely to interfere with trial completion, assessments, or interpretation of trial results, or otherwise would make the subject an inappropriate subject for this trial.
- •Pregnant and/or breastfeeding.
- •Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during the trial and for 12 weeks following the last dose of uproleselan/placebo. Women who are postmenopausal with amenorrhea for at least 1 year prior to trial entry and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status (>28U/L) will be considered NOT of childbearing potential. Highly effective contraception includes:
- •Total abstinence with a male partner.
- •Female sterilization (has had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before uproleselan/placebo. In case of oophorectomy alone, the subject would be eligible only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
- •Male sterilization (at least 6 months prior to Screening). For female subjects on the trial, the vasectomized male partner should be the sole partner for that subject.
- •BOTH of the following forms of contraception consistently used together:
- •Injected, transdermal, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%) with the exception of intrauterine devices, which are excluded due to the risk of infection and bleeding.
- •Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with or without spermicidal foam/gel/film/cream/vaginal suppository.
- •Men who are sexually active and not willing to use condoms during the trial and for 12 weeks following the last dose of uproleselan/placebo, unless they have undergone vasectomy for sterilization (at least 6 months prior to Screening), are excluded from trial participation.
- •Men who are sexually active and not willing to use condoms during the trial and for 12 weeks following the last dose of uproleselan/placebo, unless they have undergone vasectomy for sterilization (at least 6 months prior to Screening), are excluded from trial participation.
研究组 & 干预措施
Uproleselan + Standard of Care Melphalan
Experimental
- On the evening of Day -3, patients will receive dose #1 of uproleselan
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of uproleselan
- On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of uproleselan
- On Day -2 following completion of dose #3 of uproleselan, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of uproleselan
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of uproleselan
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of uproleselan
- On Day 0, 4 hours (+/- 2 hours) after the final dose of uproleselan, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
干预措施: Uproleselan (Drug)
Uproleselan + Standard of Care Melphalan
Experimental
- On the evening of Day -3, patients will receive dose #1 of uproleselan
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of uproleselan
- On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of uproleselan
- On Day -2 following completion of dose #3 of uproleselan, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of uproleselan
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of uproleselan
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of uproleselan
- On Day 0, 4 hours (+/- 2 hours) after the final dose of uproleselan, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
干预措施: Melphalan (Drug)
Placebo + Standard of Care Melphalan
Placebo Comparator
- On the evening of Day -3, patients will receive dose #1 of placebo
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of placebo On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of placebo.
- On Day -2 following completion of dose #3 of placebo, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of placebo.
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of placebo.
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of placebo.
- On Day 0, 4 hours (+/- 2 hours) after the final dose of placebo, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
干预措施: Placebo (Drug)
Placebo + Standard of Care Melphalan
Placebo Comparator
- On the evening of Day -3, patients will receive dose #1 of placebo
- On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of placebo On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of placebo.
- On Day -2 following completion of dose #3 of placebo, the patient will be administered the conditioning dose of melphalan (200mg/m^2) as per institutional practice.
- On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of placebo.
- On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of placebo.
- On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of placebo.
- On Day 0, 4 hours (+/- 2 hours) after the final dose of placebo, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment
干预措施: Melphalan (Drug)
结局指标
主要结局
Change in Diarrhea as Assessed Per CTCAE v5.0
时间窗: From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days)
Grade 0 is defined as no diarrhea, or no change from baseline. Grade 1 is defined as an increase of \<4 stools per day over baseline; mild increase in ostomy output compared to baseline. Grade 2 is defined as an increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL. Grade 3 is defined as an increase of \>=7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limited self care ADL. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. Grade 5 is defined as death.
次要结局
- Change in Oral Mucositis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Nausea as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Esophagitis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Esophageal Pain as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Abdominal Pain as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Vomiting as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Gastritis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Enterocolitis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Proctitis as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Median Change in Scores of Patient Reported Outcomes as Measured by the CTCAE Pro Form v1.0(Day -3, Day +8, date of discharge or Day +14 (whichever is sooner) (up to 18 days))
- Median Change in Scores of Quality of Life as Measured by the CTCAE Pro Form v 1.0(Day -3, Day +8, date of discharge or Day +14 (whichever is sooner) (up to 18 days))
- Change in Hemorrhoids as Assessed Per CTCAE v5.0(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Time to Neutrophil Engraftment(Through date of discharge (up to be 18 days))
- Change in Nutritional Status as Assessed by Total Parenteral Nutrition (TPN) Days(Before conditioning and at day +14 or date of discharge (whichever is sooner) (up to be 18 days))
- Duration of Hospital Length of Stay(From date of admission for auto-HCT to date of discharge (up to be 18 days))
- Incidence of Infection Assessed by Rates of Bacteremia (With Organism Reported When Available)(Through date of discharge (upto be 18 days))
- Time to First Antibiotics(Through date of discharge (up to be day 18))
- Median Daily Dose of Anti-diarrheal Medications(Through date of discharge (up to be 18 days))
- Change in Bristol Stool Scale(From day -3 to date of discharge or day 14 (whichever is sooner) (up to be 18 days))
- Change in Nutritional Status as Assessed by Change in Standing Weight(Day -3, Day 8, and date of discharge or Day 14 (whichever is sooner) (up to be 18 days))
- Incidence of Clostridium Difficile Infections(Through date of discharge (up to be 18 days))
- Median Daily Dose of Pain Medications(Through date of discharge (up to be 18 days))
研究者
研究点 (1)
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