Budesonide for the Treatment Multiple Myeloma in Patients Undergoing Autologous Stem Cell Transplant, IMPACT Study

PRIMARY OBJECTIVE:

I. To assess the impact of budesonide prophylaxis on transplant related outcomes in patients with multiple myeloma undergoing ASCT. (Run-in phase)

II. To assess the impact of budesonide prophylaxis plus standard of care (SOC) versus standard of care (SOC) alone on the incidence of >= Grade 2 diarrhea (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) in multiple myeloma patients receiving high-dose melphalan in preparation for ASCT. (Randomized phase)

SECONDARY OBJECTIVES:

I. To demonstrate the superiority of prophylactic budesonide plus standard of care compared to standard of care in reducing diarrhea as measured by Patient-Reported Outcome Common Terminology Criteria (PRO-CTCAE) (gastrointestinal [GI] domain, fatigue, mouth sore, concentration, and memory).). (Randomized phase)

II. To demonstrate the superiority of prophylactic budesonide plus standard of care compared to standard of care in reducing alternative gastrointestinal (GI) toxicities (e.g. abdominal pain, nausea) as measured by Patient-Reported Outcome Common Terminology Criteria (PRO-CTCAE) (GI domain, fatigue, mouth sore, concentration, and memory). (Randomized phase)

III. To assess the effects of prophylactic budesonide plus SOC compared to SOC. (Randomized phase)

IV. To assess the effects of prophylactic budesonide plus SOC compared to SOC on patient reported outcomes (PRO) and quality of life (QoL), assessed on Day -1, Day 14, end of treatment (EOT), and at the Day 30 visit. (Randomized phase)

V. To assess the impact of budesonide prophylaxis on engraftment syndrome in patients with multiple myeloma undergoing ASCT. (Randomized phase)

VI. To descriptively assess in both the prophylactic budesonide arm and the standard of care arms the following toxicities as measured by Patient-Reported Outcome Common Terminology Criteria (PRO-CTCAE) (Randomized phase):

VIa. Mouth Sores;

VIb. Concentration;

VIc. Problems with memory;

VId. Fatigue.

EXPLORATORY OBJECTIVES:

I. To assess the impact of budesonide prophylaxis on engraftment syndrome in patients with multiple myeloma undergoing ASCT. (Run-in phase)

II. To demonstrate the superiority of prophylactic budesonide plus standard of care compared to standard of care in reducing diarrhea as measured by Patient-Reported Outcome Common Terminology Criteria (PRO-CTCAE) (GI domain, fatigue, mouth sore, concentration, and memory). (Run-in phase)

III. To demonstrate the superiority of prophylactic budesonide plus standard of care compared to standard of care in reducing alternative gastrointestinal (GI) toxicities (e.g. abdominal pain, nausea) as measured by Patient-Reported Outcome Common Terminology Criteria (PRO-CTCAE) (GI domain, fatigue, mouth sore, concentration, and memory). (Run-in phase)

IV. To assess the effects of prophylactic budesonide plus SOC compared to SOC. (Run-in phase)

V. To assess the effects of prophylactic budesonide plus SOC compared to SOC on patient reported outcomes (PRO) and quality of life (QoL), assessed on Day -1, Day 14, end of treatment (EOT), and at the Day 30 visit. (Run-in phase)

VI. To descriptively assess in both the prophylactic budesonide arm and the standard of care arms the following toxicities as measured by Patient-Reported Outcome Common Terminology Criteria (PRO-CTCAE) (Run-in phase):

VIa. Mouth Sores;

VIb. Concentration;

VIc. Problems with memory;

VId. Fatigue.

VII. To assess the degree of correlation between PRO-CTCAE to standard investigator assessed CTCAE scoring. (Randomized phase)

VIII. To assess overall survival in this study population at 3 months post transplant. (Randomized phase)

IX. To assess progression free survival (PFS) in this study population at 3 months post transplant. (Randomized phase)

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients receive budesonide orally (PO) three times a day (TID) on days -1 through day 14 post-transplant in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO TID on days -1 through day 14 post-transplant in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and 3 months.