Study of Melphalan HCl for Injection (Propylene Glycol-free), Carmustine, Etoposide, Cytarabine (BEAM Regimen) and Autologous Stem Cell Transplantation for Lymphoma

A Phase II Study of Melphalan HCl for Injection (Propylene Glycol-free), Combined With Carmustine, Etoposide, and Cytarabine (BEAM Regimen) for Myeloablative Conditioning in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation

Phase II study is being conducted to confirm the safety and efficacy of high-dose Melphalan HCl for Injection (Propylene Glycol-Free) when included in the BEAM regimen for myeloablative conditioning in lymphoma patients undergoing ASCT

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin; Hodgkin Disease
• Intervention / Treatment: Drug: Cytarabine; Drug: Carmustine; Drug: Etoposide phosphate; Drug: Melphalan HCl (propylene glycol-free)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Hodgkin lymphoma or non-Hodgkin lymphoma.
• Eligible for autologous stem cell transplantation.
• 18 to 75 years of age at time of enrollment.
• Adequate autologous graft, defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 x 10^6 CD34+ cells/kg based on patient body weight
• ECOG performance status ≤ 2

• Normal organ function as defined below:

  • Creatinine clearance > 40 ml/min
  • Total bilirubin ≤2.0 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • LVEF > 40% (by ECHO or MUGA)
  • FEV1 > 50% of predicted and DLCO > or = 50% of predicted
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria:

• A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Currently receiving any other experimental therapy or has received any other experimental therapy within the 4 weeks prior to enrollment.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan HCl for injection (propylene glycol-free), Captisol, or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding women. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
• Known HIV-positivity. These patients are excluded because of the potential for pharmacokinetic interactions with the study regimen and their antiretroviral therapy and because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melphalan, carmustine, etoposide, cytarabine (BEAM); Day -7, carmustine intravenous (IV) infusion; Days -6, -5, -4, and -3, etoposide and cytarabine (IV) infusions twice a day; Day -2, melphalan HCl (propylene glycol-free)(IV) infusion; Day 0, stem cell transplant.	Drug: Cytarabine; Other Names: Ara-C; Arabinosylcytosine; Cytosar-U ®; 1-β-Arabinofuranosylcytosine; Cytosine arabinoside; Drug: Carmustine; Other Names: BCNU; BiCNU®; Drug: Etoposide phosphate; Other Names: Vepesid; VP-16; Drug: Melphalan HCl (propylene glycol-free)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events	Adverse events will be assessed using the National Cancer Institute (NCI)-CTCAE version 4.0. Number of events, grade 2 or higher, occurring in 10% or greater of participants. Grade 2 diarrhea and Grade 2 nausea/vomiting were not recorded.	Day -7 through Day 30
Treatment-related Mortality (TRM)	TRM is defined as death not due to progressive lymphoma prior to Day 100 after transplant	100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as Measured by Response Rates	The response rates according to each category of response Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) will be summarized by the proportion of patients meeting each criterion.; Evaluated using PET or CT scan and Revised Response Criteria for Malignant Lymphoma	Up to Day 100
Disease-free Survival	Percentage of patients who survive without any signs or symptoms of cancer at 1 year.	1 year
Disease-free Survival	Percentage of patients who survive without any signs or symptoms of cancer at 2 years.	2 years
Time to Engraftment (Neutrophil)	Time from the date of the transplant to the date of neutrophil engraftment.	Assessed up to day 30
Time to Engraftment (Platelet)	Time from the date of transplant to the date of platelet engraftment.	Assessed up to day 100

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2014
• Primary Completion (Actual): September 30, 2015
• Study Completion (Actual): May 31, 2017

Study Registration Dates

• First Submitted: October 16, 2013
• First Submitted That Met QC Criteria: October 21, 2013
• First Posted (Estimate): October 25, 2013

Study Record Updates

• Last Update Posted (Actual): February 13, 2018
• Last Update Submitted That Met QC Criteria: January 16, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Etoposide phosphate; Melphalan; Cytarabine; Carmustine
• Other Study ID Numbers: 201312115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No