A Study of Melphalan in People With Lymphoma Getting an Autologous Hematopoietic Cell Transplant

Phase 1

Recruiting

• Conditions: Lymphoma, B-Cell; Lymphoma, T-Cell; Lymphoma; Lymphoma, Hodgkin; Lymphoma, Non-Hodgkin
• Interventions: Other: Pharmacokinetics

• Registration Number: NCT05540340
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary

The purpose of this study is to find out whether it is practical to use a newer way to calculate melphalan dose given (called population PK model) in BEAM chemotherapy before AHCT. Standard dose is fixed for everybody and is calculated using height and weight. The population PK model, tested in this study, uses information based on people who have previously received melphalan and aims to calculate an optimal dose separately for each person. Study researchers think that the dose calculated using the population PK model may still be effective but have less side effects than the standard melphalan dose.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-09
• Study First Submitted: 2022-09-12
• Study First Submitted QC: 2022-09-12
• Study First Posted: 2022-09-14
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-19
• Last Update Posted: 2024-06-21
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Age18 - 79 years old
• Diagnosed with any type of lymphoma [Hodgkin, non-Hodgkin (B- or T-cell)] and planned for BEAM-AHCT
• KPS > 70
• Cardiac ejection fraction of > 45%
• Hemoglobin-adjusted diffusing capacity of carbon monoxide (DLCO) of ≥45%
• Creatinine clearance of ≥ 40 mL/min
• Completion of most recent systemic therapy within 12 weeks of enrollment
• Complete or partial response to systemic chemotherapy by IWG Working Group Criteria.
• Total bilirubin < 2.0 mg/dL in the absence of suspected Gilbert's disease (if Gilbert's disease is suspected, the total bilirubin must be ≤3.0 mg/dL), and AST & ALT < 2.5 ULN.
• Minimum stem cell dose of 2 x 10*6 CD34+ cells/kg

Exclusion Criteria

• Disease progression by IWG Working Group since last therapy
• Pregnant or lactating females
• Contraindication to CE melphalan or any of the required supportive treatments, including hypersensitivity to G-CSF or pegfilgrastim
• Any known allergy or allergic reactions to Captisol
• Any other medical condition or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1: Pharmacokinetic directed melphalan	Pharmacokinetics	This is a feasibility study of pharmacokinetic (PK)-directed Captisol Enabled (CE) melphalan dosing to target an AUC of 8.5 (+/- 1.5) using a population PK model in lymphoma patients receiving BEAM \[carmustine (BCNU) (B), etoposide (E), cytarabine (Ara-C) (A), and melphalan (M)\], followed by autologous hematopoietic cell transplantation (AHCT). This study will enroll patients with lymphoma planned for BEAM-AHCT. Carmustine IV will be given on day -6, followed by etoposide IV and cytarabine IV from day -5 to -2 as per the MSK inpatient or outpatient standard of care. The calculated melphalan dose based on population PK model to achieve the proposed melphalan target exposure \[8.5 (+/- 1.5) mg\*h/L\], will be administered on day -1, and six peripheral blood samples of 5 ml in lithium heparin tubes will be collected at 5, 15, 30, 40, 75, and 150 minutes after the melphalan, for PK testing to determine if the goal AUC was achieved.
Cohort 2: Pharmacokinetic directed melphalan	Pharmacokinetics	In cohort 2, carmustine will be on Day -7, cytrabine and etoposide on Day -6 to Day -3, and melphalan (70mg/m2 /day IV) will be administered on day -2 followed by PK samples to determine the melphalan dose on day -1 using the population PK model. PK samples will be collected again after the dose on day -1 to confirm the total melphalan AUC of 8.5 (+/- 1.5) mg\*h/L. Six peripheral blood samples of 5 ml in lithium heparin tubes will be collected at 5, 15, 30, 40, 75, and 150 minutes after the melphalan, for PK testing. The first four time points are +/- 2 min and the last two time points are +/- 5 minutes.

Primary Outcome Measures

Name	Time	Method
determine if this target AUC can be achieved	1 year	within a range of 8.5 (+/- 1.5) mg\*h/L using population PK model.

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States