PK-Directed Melphalan Before Autologous Transplant

PRIMARY OBJECTIVES: I. Measure achievement of target melphalan systemic exposure in the first 20 patients. II. Identify safety and preliminary efficacy within each systemic exposure range of melphalan using a 5+5 design. SECONDARY OBJECTIVES: I. Describe International Myeloma Working Group response levels and selected grade 3/4 toxicities in an expansion set of patients at the recommended phase 2 area under the curve (AUC) range. II.

Measure deoxyribonucleic acid (DNA) repair score from formalin-fixed paraffin-embedded diagnostic bone marrow sample (FFPE) and from pretransplant marrow aspirate sample. III. Assess melphalan-induced DNA damage in peripheral blood mononuclear cells (PBMCs) from melphalan-treated patients. IV. To correlate peripheral blood CMMCs numbers obtained with CELLSEARCH with MRD assessment at day+90. OUTLINE: This is a dose-escalation study.

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.

Registro actualizado en ClinicalTrials.gov →

• 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
• Be eligible and appropriate per the treating physician to receive 200 mg/m^2
• If enrolling in phase B of the protocol, the transplant must be part of first line therapy to provide some level of homogeneity for toxicity assessment and preliminary efficacy

Criterios de inclusión tal como figuran en el registro, recortados. La lista completa, con las exclusiones, está en el registro actualizado.