Budesonide for Multiple Myeloma

(IMPACT Trial)

Overseen By Catherine Cromar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Oral budesonide, Investigational agents

Disqualifiers: Hepatic impairment, Inflammatory bowel disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

120 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for prohibited medications, lasting at least five half-lives or 14 days, whichever is shorter, before starting treatment. If you are currently taking oral budesonide, you must stop before enrolling.

Is budesonide generally safe for use in humans?

Budesonide has been shown to be well tolerated in treating asthma in both children and adults, with over 20 years of clinical use. It does not affect important body functions like bone density or growth at the doses used for asthma, and it is considered safe for use during pregnancy. ^{1 2 3 4 5}

How is the drug Budesonide EC unique for treating multiple myeloma?

Budesonide EC is unique for treating multiple myeloma because it is primarily known as a corticosteroid used for asthma and other inflammatory conditions, and its use in multiple myeloma represents a novel application of its anti-inflammatory properties in a cancer setting. ^{3 4 5 6 7}

Research Team

Ghulam Rehman Mohy-ud-din, MBBS

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

Adults diagnosed with multiple myeloma undergoing autologous stem cell transplant (ASCT) can join this trial. They must be fit for ASCT, have proper liver function, and women of childbearing potential must not be pregnant. Exclusions include prior budesonide use, other investigational drugs without approval, severe liver issues, certain bowel diseases or chronic diarrhea, previous allogeneic stem cell transplant, active brain metastases without stable treatment or hypersensitivity to melphalan or budesonide.

Inclusion Criteria

I have multiple myeloma or Plasma Cell Leukemia and am fit for a stem cell transplant with melphalan.

I am 18 years old or older.

My liver is functioning within the required limits.

Exclusion Criteria

I am currently taking oral budesonide.

I have had a stem cell transplant from a donor.

I have stopped taking certain medications as required, for at least 5 half-lives or 14 days before starting treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-In

Safety run-in phase with 20 patients to monitor for safety signals such as engraftment failure or severe infections

18 days

Randomized Treatment

Participants are randomized to receive either budesonide or placebo to assess the impact on diarrhea and other toxicities

14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of fatigue, memory, and other symptoms

3 months

Treatment Details

Interventions

• Budesonide EC
• Placebo

Trial Overview The study is testing if Budesonide reduces the occurrence of moderate to severe diarrhea in patients with multiple myeloma who are receiving an autologous stem cell transplant. It's a phase 2 trial where participants will either receive Budesonide EC or a placebo randomly after a run-in period involving 20 patients.

Participant Groups

Group I: Run-In Phase Experimental Treatment 1 Intervention

Budesonide EC 3 mg three times a day, oral

Group II: Arm 1: Treatment Experimental Treatment 1 Intervention

Budesonide EC 3 mg three times a day, oral

Group III: Arm 2: Placebo Placebo Group 1 Intervention

Placebo 3 mg three times a day, oral

Budesonide EC is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Entocort EC for:

• Crohn's disease
• Ulcerative colitis
• Asthma
• Allergic rhinitis

Approved in European Union as Entocort EC for:

• Crohn's disease
• Ulcerative colitis
• Asthma
• Allergic rhinitis
• Microscopic colitis
• Eosinophilic esophagitis
• Primary immunoglobulin A nephropathy

Approved in Canada as Pulmicort Flexhaler for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)

Approved in Japan as Uceris for:

• Ulcerative colitis

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Findings from Research

In a 12-week study involving 338 adults with mild to moderate asthma, the combination of formoterol and budesonide significantly improved pulmonary function and asthma symptoms compared to budesonide alone, with a notable increase in morning peak expiratory flow (PEF).

The combination therapy was also better tolerated than conventional non-corticosteroid treatments, showing fewer incidences of asthma deterioration, making it the safest and most effective option for long-term asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of formoterol (Oxis) turbuhaler plus budesonide (Pulmicort) turbuhaler in mild to moderate asthma: a comparison with budesonide Turbuhaler alone and current non-corticosteroid therapy in Russia. Chuchalin, AG., Ovcharenko, SI., Goriachkina, LA., et al.[2015]

In a study involving 159 adults with moderate-to-severe asthma, budesonide delivered via an inhaler significantly reduced the need for oral glucocorticosteroids (GCSs) by 79-83% compared to only 27% in the placebo group, indicating its efficacy in managing asthma while minimizing systemic steroid use.

Approximately two-thirds of participants using budesonide were able to completely stop oral corticosteroids, and they also experienced improvements in lung function and asthma symptoms, suggesting that budesonide not only spares oral GCSs but also maintains or enhances asthma control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group. Nelson, HS., Bernstein, IL., Fink, J., et al.[2019]

Budesonide inhalation suspension significantly improves both nighttime and daytime asthma symptoms in children under 4 years and those 4 years and older, based on a retrospective analysis of two randomized studies involving children aged 6 months to 8 years.

The treatment is generally safe, with no significant differences in adverse events between age groups, although a notable effect on hypothalamic-pituitary-adrenal-axis function was observed in younger children at the lowest dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily budesonide inhalation suspension in infants and children or = 4 years of age with persistent asthma. Scott, MB., Ellis, MH., Cruz-Rivera, M., et al.[2019]

Budesonide, an inhaled corticosteroid, is effective in controlling mild-to-moderate persistent asthma in patients aged 12 months and older, with a well-established safety profile over 20 years of clinical use.

It does not negatively impact important health factors like the hypothalamic-pituitary-adrenal axis, bone mineral density, or growth, making it a safe option for long-term asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of budesonide in adults and children with mild-to-moderate persistent asthma. Banov, CH.[2019]

In a study involving 177 adults with persistent asthma, once-daily administration of budesonide Turbuhaler (400 microg) significantly improved lung function (FEV1) and reduced asthma symptoms compared to placebo over a 12-week period.

The treatment was found to be safe, with adverse events being mostly mild or moderate and similar in frequency to those in the placebo group, indicating that budesonide is a viable option for inhaled corticosteroid-naive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily budesonide via Turbuhaler improves symptoms in adults with persistent asthma. Banov, CH., Howland, WC., Lumry, WR.[2006]

Budesonide, an inhalation glucocorticosteroid, significantly improved asthma symptoms in 20 patients, showing a response by the end of the first week of treatment, with a notable reduction in acute asthma episodes and decreased reliance on short-acting beta 2-agonists.

After 12 months of treatment, budesonide improved lung function, as indicated by a 31% reduction in peak expiratory velocity variability, but did not fully normalize the bronchial mucosa, suggesting that longer treatment may be necessary for complete recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinicomorphological assessment of budesonide efficiency in patients with bronchial asthma]. Budkova, AA., Volkova, LI., Budkov, SR., et al.[2006]

A review of 34 controlled clinical studies involving 4466 adults and adolescents, and 1532 children with asthma shows that once-daily budesonide is as effective as twice-daily regimens for treating mild-to-moderate asthma.

Budesonide is well tolerated and simplifies treatment regimens, potentially improving patient compliance, making it a suitable option for both initial and maintenance therapy in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily inhaled budesonide for the treatment of asthma: clinical evidence and pharmacokinetic explanation. Selroos, O., Edsbäcker, S., Hultquist, C.[2019]

References

1. India pubmed.ncbi.nlm.nih.gov

The safety and efficacy of formoterol (Oxis) turbuhaler plus budesonide (Pulmicort) turbuhaler in mild to moderate asthma: a comparison with budesonide Turbuhaler alone and current non-corticosteroid therapy in Russia. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Once-daily budesonide inhalation suspension in infants and children or = 4 years of age with persistent asthma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The role of budesonide in adults and children with mild-to-moderate persistent asthma. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Once-daily budesonide via Turbuhaler improves symptoms in adults with persistent asthma. [2006]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinicomorphological assessment of budesonide efficiency in patients with bronchial asthma]. [2006]

7. England pubmed.ncbi.nlm.nih.gov

Once-daily inhaled budesonide for the treatment of asthma: clinical evidence and pharmacokinetic explanation. [2019]