About this trial
This phase I trial studies the best dose and side effects of mephalan in treating patients with multiple myeloma who are undergoing stem cell transplant. Chemotherapy drugs, such as mephalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial uses a new method of dosing that is based on analysis of each individual's blood levels of melphalan after receiving a part of the dose, termed pharmacokinetic analysis. This may help to learn more about how to dose melphalan correctly and which patients are likely to benefit from a personalized dose.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient must have the clinical diagnosis of a plasma cell neoplasm requiring treatment per the treating physician using the International Myeloma Working Group (IMWG) and World Health Organization (WHO) criteria as guidelines. This can include extraosseous plasmacytoma, monoclonal immunoglobulin deposition disease, and heavy-chain diseases as these diagnoses, while rare, can be treated in part with autologous transplant
If enrolling in phase A of this protocol, the patient
must have received 2+ lines of therapy as defined by the IMWG; and
Must have estimated glomerular filtration rate (eGFR) by Cockcroft-Gault > 40 mL/min; and
Disqualifiers
Patients known to meet criteria for progressive disease or clinical relapse between screening and planned melphalan infusion day -3
Subject has any of the following cardiac abnormalities
History of clinically significant cardiovascular disease with New York Heart Association class III or IV congestive heart failure or
Severe non-ischemic cardiomyopathy or
Trial design
Single group
Treatments tested in this trial
Autologous Hematopoietic Stem Cell Transplantation
Procedure/SurgeryUndergo ASCT
Melphalan
DrugGiven IV
Questionnaire Administration
Other interventionAncillary studies
Treatment groups
Trial outcomes
Primary outcomes
Predicted versus observed total melphalan area under the curve (AUC)
Will be measured using pharmacokinetic data from the day -3 and day -1 dose.
Incidence of exposure limiting toxicity
Will measure proportion of patients with clinically significant mucositis, tachyarrhythmia, and delayed engraftment. Toxicity will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) guidelines.
Minimal residual disease (MRD) negativity post-transplant
MRD status will be determined per International Myeloma Working Group (IMWG) criteria using next generation sequencing in patients with suspected complete response (CR).
Secondary outcomes
Overall response rate
The number and percentage of subjects experiencing objective response will be descriptively summarized overall and by cohort. Responders will be defined as those that achieve best response of partial response (PR) or better defined according to the IMWG Uniform response criterion. CR rate will be calculated with an exact 95% confidence interval, both within cohorts but not between cohorts.
Incidence of selected grade 3/4 toxicities at the recommended AUC range
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Adverse events will be summarized and described within each cohort. They will initially be reviewed regardless of attribution, but also whether they are possibly, probably, or definitely related to treatment. In addition, will review all adverse event data that are graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe adverse events or toxicities will be described. Will assess the proportion of patients who experience grade 3 or higher non-hematologic toxicity. To assess tolerability, will also capture the proportion of patients who go off treatment due to adverse events.
Sponsors and contacts
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Emory University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Gateway for Cancer Research
Collaborator