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

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

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.

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.

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 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

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.