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

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.

Inclusion criteria

• Patients must be aged 18 years or older.
• Patient must understand and voluntarily signed an informed consent form.
• Patient must be willing and able to adhere to the study schedule and other protocol requirements.
• Histologically confirmed multiple myeloma prior to enrollment and randomization.
• Eligible for hematopoietic stem cell mobilization and autologous hematopoietic stem cell transplantation as per institutional guidelines.
• Females of reproductive potential must use effective contraception during treatment with motixafortide and for 8 days after the final dose.

Exclusion criteria

• Previous history of autologous or allogeneic hematopoietic cell transplantation.
• History of hemoglobin SS disease or hemoglobin S trait precluding the patient's ability to use G-CSF.
• History of steroid-induced psychosis or encephalopathy requiring medical intervention.
• History of type I or II diabetes mellitus that is poorly controlled or with high glucose variability precluding safe administration of dexamethasone 12mg IV as premedication in the opinion of the investigator.
• History of serious systemic reaction to motixafortide.