This phase IV trial seeks to evaluate the feasibility of using population pharmacokinetic (PK) modeling to personalize drug dosage in lymphoma patients receiving carmustine, etoposide, cytarabine, and melphalan hydrochloride/sulfobutyl ether beta-cyclodextrin complex (melphalan) followed by autologous hematopoietic stem cell transplant (BEAM-AHCT). Pharmacokinetics refers to the way the body absorbs, distributes, and gets rid of a drug. Population PK modeling uses PK information based on people who have previously received the drug to calculate the drug's optimal dose. Chemotherapy drugs, such as carmustine, cytarabine and melphalan, 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. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid repair and may kill cancer cells. Giving chemotherapy before a stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells to grow. However, standard dosages of chemotherapy drugs like melphalan can have significant side effects. Using the population PK model may allow researchers to calculate an optimal dose for melphalan, which would be just as effective at killing cancer cells as the standard dosage, but have fewer side effects.
Additional locations may be listed on ClinicalTrials.gov for NCT05540340.
Locations matching your search criteria
United States
New York
New York
Memorial Sloan Kettering Cancer CenterStatus: Active
Contact: Parastoo Bahrami Dahi
Phone: 646-608-3733
PRIMARY OBJECTIVE:
I. To evaluate the feasibility of personalized drug dosing using a population pharmacokinetic (PK) model to target a melphalan hydrochloride/sulfobutyl ether beta-cyclodextrin complex (melphalan) area under the curve (AUC) of 8.5 (+/- 1.5) mg*h/L, in lymphoma patients undergoing BEAM-AHCT.
SECONDARY OBJECTIVES:
I. To estimate the incidence of grade >= 3 mucositis.
II. To estimate the incidence of grade >= 3 non-hematologic toxicities (other than mucositis).
III. To estimate disease response at 3 and 12 months post transplant.
IV. To examine hospital length of stay (for outpatient transplants it will be counted from the first day of conditioning regimen on red team through last day of daily visits inclusive of hospital admission days).
V. To estimate the incidence of neutrophil and platelet engraftment.
VI. To estimate the incidence of treatment-related mortality (TRM) at days 100 and 365 following transplant.
VII. To estimate progression-free survival (PFS) at 12-months.
VIII. To estimate overall survival (OS) at 12-months.
IX. To quantify patient reported symptom burden peri-AHCT.
CORRELATIVE STUDIES:
I. Deoxyribonucleic acid (DNA) adduct testing to evaluate if the extent of DNA damage, as measured by DNA monoadduct and interstrand cross-links formation, correlates with the AUC and toxicity.
II. Genomic profiling of cell-free DNA (cfDNA) in blood will be used for the detection of genetic alterations that can predict treatment outcome and has been utilized as an early surrogate for disease recurrence.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT 1: Patients receive carmustine intravenously (IV) over 2 hours on day -6, etoposide IV over 1 hour and cytarabine IV on days -5 to -2. Patients then receive melphalan IV over 30 minutes on day -1 based on population pharmacokinetic modeling and undergo CD34+ autologous hematopoietic stem cell transplantation (AHCT) on day 0. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening, computed tomography (CT) or positron emission tomography (PET) during follow up, and collection of blood samples throughout the study.
COHORT 2: Patients receive carmustine IV over 2 hours on day -7, etoposide IV over 1 hour and cytarabine IV on days -6 to -3. Patients then receive melphalan IV over 30 minutes on days -2 and -1 based on population pharmacokinetic modeling and undergo CD34+ AHCT on day 0. Patients undergo ECHO or MUGA during screening, CT or PET during follow up, and collection of blood samples throughout the study.
After completion of study treatment, patients are followed up daily until engraftment and then in months 1, 3, 6, 9, and 12.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorParastoo Bahrami Dahi
