Clinical trial NCT05405387: Impact of Budesonide on Incidence of ≥ Gr2 Diarrhea in Multiple Myeloma (MM) Patients Undergoing Autologous Stem Cell Transplant
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2022-06-06
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Stage one is open-label safety run-in. Stage 2 is randomized, placebo-controlled.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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. 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Proportion of patients with delayed engraftment (engraftment after day 18) and severe infection related complications (≥ Grade 4 NCI CTCAE v5).
timeFrame: 18 days
measure: 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).
timeFrame: 14 days
Secondary outcomes:
measure: proportion of patients reporting "frequent" or "almost constant" diarrhea on Day -1 of transplant on the PRO-CTCAE score
timeFrame: Day -1
measure: proportion of patients reporting "frequent" or "almost constant" diarrhea on Day 7 of transplant on the PRO-CTCAE score
timeFrame: Day 7
measure: proportion of patients reporting "frequent" or "almost constant" diarrhea on Day 14 of transplant on the PRO-CTCAE score
timeFrame: Day 14
measure: proportion of patients reporting "frequent" or "almost constant" diarrhea on Day 30 of transplant on the PRO-CTCAE score
timeFrame: Day 30
measure: proportion of patients reporting "frequent" or "almost constant" diarrhea 3 months post ACST on the PRO-CTCAE score
timeFrame: 3 Months
measure: proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day -1 of transplant on the PRO-CTCAE score
timeFrame: Day -1
measure: proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day 7 aof transplant on the PRO-CTCAE score
timeFrame: Day 7
measure: proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day 14 of transplant on the PRO-CTCAE score
timeFrame: Day 14
measure: proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain on Day 30 of transplant on the PRO-CTCAE score
timeFrame: Day 30
measure: proportion of patients in each arm reporting "frequent" or "almost constant" abdominal pain 3 months post ACST on the PRO-CTCAE score
timeFrame: 3 months
measure: proportion of patients in each arm reporting "frequent" or "almost constant" nausea on Day 1 of transplant on the PRO-CTCAE score
timeFrame: Day -1
measure: proportion of patients in each arm reporting "frequent" or "almost constant" nausea on Day 7 of transplant on the PRO-CTCAE score
timeFrame: Day 7
measure: proportion of patients in each arm reporting "frequent" or "almost constant" nausea on Day 14 of transplant on the PRO-CTCAE score
timeFrame: Day 14
measure: The proportion of patients in each arm reporting "frequent" or "almost constant" nausea on Day 30 of transplant on the PRO-CTCAE score.
timeFrame: Day 30
measure: The proportion of patients in each arm reporting "frequent" or "almost constant" nausea 3 months post ACST on the PRO-CTCAE score.
timeFrame: 3 months
measure: The proportion of patients in each arm reporting "frequent" or "almost constant" vomiting on Day 1 of transplant on the PRO-CTCAE score.
timeFrame: Day -1
measure: The proportion of patients in each arm reporting "frequent" or "almost constant" vomiting on Day 7 of transplant on the PRO-CTCAE score.
timeFrame: Day 7
measure: The proportion of patients in each arm reporting "frequent" or "almost constant" vomiting on Day 14 of transplant on the PRO-CTCAE score.
timeFrame: Day 14
measure: The proportion of patients in each arm reporting "frequent" or "almost constant" vomiting on Day 30 of transplant on the PRO-CTCAE score.
timeFrame: Day 30
measure: The proportion of patients in each arm reporting "frequent" or "almost constant" vomiting 3 months post ACST on the PRO-CTCAE score.
timeFrame: 3 months
measure: Length of stay in hospital
timeFrame: up to 30 days
measure: Time to engraftment
timeFrame: up to 30 days
measure: Proportion of patients using supportive anti-diarrheal and pain medications
timeFrame: up to 30 days
measure: Change in Bristol Stool Scale
timeFrame: up to 30 days
measure: Incidence of post ASCT infection prior to engraftment
timeFrame: up to 30 days
measure: Median score of EORTC QLQ-C30 for participants in each arm
timeFrame: 6 weeks
measure: proportion of patients with engraftment syndrome
timeFrame: up to 30 days
measure: Proportion of patients reporting none, mild, moderate, severe or very severe mouth sores as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, mild, moderate, severe or very severe mouth sores as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, mild, moderate, severe or very severe mouth sores as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, mild, moderate, severe or very severe mouth sores as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, mild, moderate, severe or very severe mouth sores as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very mouth interference with daily activity as a result of their mouth sores as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very mouth interference with daily activity as a result of their mouth sores as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very mouth interference with daily activity as a result of their mouth sores as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very mouth interference with daily activity as a result of their mouth sores as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very mouth interference with daily activity as a result of their mouth sores as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with concentration as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with concentration as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with concentration as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with concentration as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with concentration as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of concentration problems as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of concentration problems as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of concentration problems as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of concentration problems as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of concentration problems as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with memory as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with memory as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with memory as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with memory as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, mild, moderate, severe or very severe problems with memory as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of problems with memory as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of problems with memory as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of problems with memory as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of problems with memory as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of problems with memory as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
measure: Proportion of patients reporting none, mild, moderate, severe or very severe fatigue as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, mild, moderate, severe or very severe fatigue as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, mild, moderate, severe or very severe fatigue as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, mild, moderate, severe or very severe fatigue as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, mild, moderate, severe or very severe fatigue as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of fatigue as measured by PRO-CTCAE on Day -1
timeFrame: Day -1
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of fatigue as measured by PRO-CTCAE on Day 7
timeFrame: Day 7
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of fatigue as measured by PRO-CTCAE on Day 14
timeFrame: Day 14
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of fatigue as measured by PRO-CTCAE on Day 30
timeFrame: Day 30
measure: Proportion of patients reporting none, a little bit, somewhat, quite a bit or very much interference with daily activity as a result of fatigue as measured by PRO-CTCAE 3 months post ACST
timeFrame: 3 months
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at the University of Utah
state: Utah
Study officials:
affiliation: Huntsman Cancer Institute
name: Ghulam Rehman Mohy-ud-din, MBBS
role: PRINCIPAL_INVESTIGATOR
References: