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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05540340

Collaborator

(none)

Enrollment

Location

Arm

11.7

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Lymphoma, B-Cell Lymphoma, T-Cell Lymphoma, Hodgkin Lymphoma, Non-Hodgkin	Other: Pharmacokinetics	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pharmacokinetic Directed Melphalan for Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation

Actual Study Start Date :

Sep 9, 2022

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pharmacokinetic directed melphalan 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 20 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.	Other: Pharmacokinetics 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.

Arm

Intervention/Treatment

Experimental: Pharmacokinetic directed melphalan

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 20 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.

Other: Pharmacokinetics

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.

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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