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

Phase 2

Completed

Interventions: Drug: Carmustine
Drug: Etoposide phosphate
Drug: Cytarabine
Drug: Melphalan HCl (propylene glycol-free)

Brief Summary: 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

Recruitment & Eligibility

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. .

Arm && Interventions

Group	Intervention	Description
Melphalan, carmustine, etoposide, cytarabine (BEAM)	Cytarabine	* 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.
Melphalan, carmustine, etoposide, cytarabine (BEAM)	Etoposide phosphate	* 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.
Melphalan, carmustine, etoposide, cytarabine (BEAM)	Melphalan HCl (propylene glycol-free)	* 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.
Melphalan, carmustine, etoposide, cytarabine (BEAM)	Carmustine	* 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.

Primary Outcome Measures

Name	Time	Method
Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events	Day -7 through Day 30	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.
Treatment-related Mortality (TRM)	100 days	TRM is defined as death not due to progressive lymphoma prior to Day 100 after transplant

Secondary Outcome Measures

Name	Time	Method
Efficacy as Measured by Response Rates	Up to Day 100	* 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
Disease-free Survival	2 years	Percentage of patients who survive without any signs or symptoms of cancer at 2 years.
Time to Engraftment (Neutrophil)	Assessed up to day 30	Time from the date of the transplant to the date of neutrophil engraftment.
Time to Engraftment (Platelet)	Assessed up to day 100	Time from the date of transplant to the date of platelet engraftment.

Locations (1): Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States