Impact of Budesonide on Incidence of ≥ Gr2 Diarrhea in Multiple Myeloma (MM) Patients Undergoing Autologous Stem Cell Transplant

Официальное название

A Randomized Phase 2 Trial Investigating the Impact of Budesonide Prophylaxis on Incidence of ≥ Grade 2 Diarrhea in Multiple Myeloma (MM) Patients Undergoing Autologous Stem Cell Transplant

Обзор

A randomized placebo controlled, phase 2 study of budesonide in subjects with multiple myeloma undergoing autologous stem cell transplant (ACST). The study includes a run-in period with 20 patients.

Подробное описание

The trial will initiate with a safety run-in of 20 pts with a ≥ 5 pts failing to engraft (or having a Grade 4 or higher infection rate) within 18 days as the flag for a potential safety signal.

After all 20 of the patients in the safety run-in have completed follow-up for delayed engraftment (18 days), if the trial is not stopped for a safety signal, then the trial will proceed to a randomized stage. 50 patients will be randomized to placebo and 50 patients will be randomized to budesonide.

Patients in both arms will report toxicities by responding to items from the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE.) PRO-CTCAE is a patient-reported outcome (PRO) measurement system used to evaluate symptomatic toxicity in patients on cancer clinical trials based on symptom frequency, severity, interference, amount, and presence/absence. PRO-CTCAE responses are scored from 0 (absent) to 4 (very frequent, severe, etc.), or 0/1 for absent/present.

Вмешательства

• Препарат Budesonide EC
  Subjects will take 3mg of Budesonide or placebo. Dosing will begin on day prior to cell infusion and continue until Day 14 post transplant. Budesonide or placebo will be in capsule formulation. Budesonide or Placebo will be administered orally three times daily (every 8 hours ± 1 hours) with or without food.
• Препарат Placebo
  Subjects will take 3mg of Budesonide or placebo. Dosing will begin on day prior to cell infusion and continue until Day 14 post transplant. Budesonide or placebo will be in capsule formulation. Budesonide or Placebo will be administered orally three times daily (every 8 hours ± 1 hours) with or without food.

Первичные конечные точки

• Proportion of patients with delayed engraftment (engraftment after day 18) and severe infection related complications (≥ Grade 4 NCI CTCAE v5). [Срок оценки: 18 days]
• incidence of Grade 2 or higher diarrhea from the time of ASCT until day 14 post ASCT as measured by NCI Common-Terminology Criteria (CTCAE). [Срок оценки: 14 days]

Вторичные конечные точки (12)

• proportion of patients reporting "frequent" or "almost constant" diarrhea on Day -1 of transplant on the PRO-CTCAE score [Срок оценки: Day -1]
• proportion of patients reporting "frequent" or "almost constant" diarrhea on Day 7 of transplant on the PRO-CTCAE score [Срок оценки: Day 7]
• proportion of patients reporting "frequent" or "almost constant" diarrhea on Day 14 of transplant on the PRO-CTCAE score [Срок оценки: Day 14]
• proportion of patients reporting "frequent" or "almost constant" diarrhea on Day 30 of transplant on the PRO-CTCAE score [Срок оценки: Day 30]
• proportion of patients reporting "frequent" or "almost constant" diarrhea 3 months post ACST on the PRO-CTCAE score [Срок оценки: 3 Months]
• proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day -1 of transplant on the PRO-CTCAE score [Срок оценки: Day -1]
• proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day 7 aof transplant on the PRO-CTCAE score [Срок оценки: Day 7]
• proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day 14 of transplant on the PRO-CTCAE score [Срок оценки: Day 14]
• proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day 30 of transplant on the PRO-CTCAE score [Срок оценки: Day 30]
• proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain 3 months post ACST on the PRO-CTCAE score [Срок оценки: 3 months]
• proportion of patients in each arm reporting "frequent" or "almost constant" nausea on Day 1 of transplant on the PRO-CTCAE score [Срок оценки: Day -1]
• proportion of patients in each arm reporting "frequent" or "almost constant" nausea on Day 7 of transplant on the PRO-CTCAE score [Срок оценки: Day 7]

Критерии участия

Критерии включения

• Subject aged ≥ 18 years.
• History of histologically confirmed multiple myeloma and/or Plasma Cell Leukemia diagnosis undergoing ASCT who are determined to be fit by the investigator to undergo ASCT with melphalan 200 mg/m2 or melphalan 140 mg/m2 as conditioning.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• Adequate organ function as defined as:

--Hepatic:

• Total Bilirubin ≤ 2 x institutional upper limit of normal (ULN).
• AST(SGOT)/ALT(SGPT) ≤ 5 × institutional ULN
• For female subjects who have not undergone surgical sterilization: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause or having undergone surgical sterilization (bilateral oophorectomy or hysterectomy). The following age-specific requirements apply:

• Women < 50 years of age:

• Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
• Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
• Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥ 50 years of age:

• Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
• Had radiation-induced menopause with last menses >1 year ago; or
• Had chemotherapy-induced menopause with last menses >1 year ago; or
• Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).

Inclusion Criteria required for Patients Enrolling in Safety Run-In Cohort only:

-Patient must have at least 2.5 x 106 CD34 cells in reserve for use if engraftment is delayed

Критерии исключения

• Ongoing or current use of oral budesonide at the time of enrollment.
• Receiving other investigational agents, unless deemed acceptable after consultation with the PI
• Subjects with moderate or severe pre-existing hepatic impairment as classified according to the Child-Pugh system.
• Prior history or current diagnosis of inflammatory bowel disease, microscopic colitis at baseline.
• Prior history of receiving an allogenic stem cell transplant
• Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
• Known prior severe hypersensitivity to melphalan or budesonide or any component in their formulations or compounds of similar composition (NCI CTCAE v5.0 Grade ≥ 3).
• Subjects taking prohibited medications as described in Section 6.6.1. A washout period of prohibited medications for a period of at least five half-lives or 14 days (whichever is shorter) should occur before the start of treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Huntsman Cancer Institute at the University of Utah — Salt Lake City

Идентификаторы

NCT: NCT05405387 · 152269

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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