Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic and Injection Site Reactions to Motixafortide in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization, PARADE Trial

Summary

This phase IV trial compares the effect of premedication regimens with methylprednisolone versus dexamethasone for the prevention of allergic reaction to motixafortide in patients with multiple myeloma (MM) undergoing stem cell mobilization. MM patients that receive an autologous stem cell transplantation (ASCT) have better outcomes. However, not all MM patients are able to have a successful stem cell mobilization and collection which is needed to proceed to ASCT. The addition of motixafortide prior to stem cell mobilization has allowed more MM patients to collect the needed number of stem cells to proceed to ASCT. However, motixafortide does produce systemic and injection site reactions in many patients. The optimal medication regimen to prevent reactions remains unknown. A premedication regimen with dexamethasone prior to motixafortide decreases the incidence of reactions in many patients and is considered the standard of care regimen for the prevention of systemic and injection site reactions to motixafortide in patients with MM undergoing stem cell mobilization. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen side effects/allergic reactions. However, dexamethasone is associated with other side effects like headache, difficulty sleeping, high blood glucose, high blood pressure, mood changes, fluid retention, and infection, among others. A premedication regimen with methylprednisolone prior to motixafortide may work better to decrease the incidence of reactions to motixafortide in patients with MM undergoing stem cell mobilization. Methylprednisolone is in a class of medications called corticosteroids. It works to decrease side effects/allergic reactions by changing the way the immune system works. Giving methylprednisolone may be safe, tolerable and/or more effective than dexamethasone as part of a premedication regimen for the prevention of allergic reaction to motixafortide in patients with MM undergoing stem cell mobilization.

Detailed Description

PRIMARY OBJECTIVE: I. Evaluate the safety and efficacy of a premedication regimen for motixafortide that includes loratadine, famotidine, acetaminophen, montelukast, and dexamethasone 12mg intravenously (IV) with an experimental regimen that replaces dexamethasone with methylprednisolone 125mg IV. SECONDARY OBJECTIVES: I. Compare the tolerability and patient experience between the regimens. II. Compare the effects of the two regimens on stem cell mobilization. III. Explore the potential immunomodulatory effects of the two regimens. EXPLORATORY OBJECTIVE: I. Assess the anti-myeloma activity of motixafortide. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive granulocyte colony-stimulating factor (G-CSF) once daily (QD) in the morning and loratadine orally (PO) twice daily (BID) on days 1 - 3. Patients receive G-CSF and loratadine PO once in the morning on day 4. Patients then receive loratadine PO, famotidine PO, acetaminophen PO, montelukast PO and dexamethasone IV once in the afternoon on day 4 and 1 hour later receive motixafortide subcutaneously (SC) once in the afternoon on day 4. Patients receive G-CSF once in the morning on day 5 and undergo stem cell apheresis in the morning on day 5. Patients may undergo additional stem cell apheresis on days 6, 7 and/or 8 if target dose of CD34+ cells is not achieved on day 5. Patients may receive additional G-CSF QD in the morning and loratadine PO BID on days 6, 7 and/or 8 if the target dose of CD34+ cells is not achieved on day 5. Patients undergoing additional stem cell apheresis on days 7 and 8 receive loratadine PO, famotidine PO, acetaminophen PO, montelukast PO and dexamethasone IV once in the afternoon on day 6 and 1 hour later receive motixafortide SC once in the afternoon on day 6. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive G-CSF QD in the morning and loratadine PO BID on days 1 - 3. Patients receive G-CSF and loratadine PO once in the morning on day 4. Patients then receive loratadine PO, famotidine PO, acetaminophen PO, montelukast PO and methylprednisolone IV once in the afternoon on day 4 and 1 hour later receive motixafortide SC once in the afternoon on day 4. Patients receive G-CSF once in the morning on day 5 and undergo stem cell apheresis in the morning on day 5. Patients may undergo additional stem cell apheresis on days 6, 7 and/or 8 if target dose of CD34+ cells is not achieved on day 5. Patients may receive additional G-CSF QD in the morning and loratadine PO BID on days 6, 7 and/or 8 if the target dose of CD34+ cells is not achieved on day 5. Patients undergoing additional stem cell apheresis on days 7 and 8 receive loratadine PO, famotidine PO, acetaminophen PO, montelukast PO and dexamethasone IV once in the afternoon on day 6 and 1 hour later receive motixafortide SC once in the afternoon on day 6. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection on study.

Eligibility Criteria

Interventions