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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Hodgkin Disease, Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: Carmustine
* Drug: Etoposide phosphate
* Drug: Cytarabine
* Drug: Melphalan HCl (propylene glycol-free)


Participation Criteria
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Eligibility Criteria
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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. .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melphalan, carmustine, etoposide, cytarabine (BEAM)<br>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: Carmustine<br> <br> * Other names: BiCNU®;Drug: Etoposide phosphate<br> <br> * Other names: Vepesid;Drug: Cytarabine<br> <br> * Other names: Ara-C;Drug: Melphalan HCl (propylene glycol-free)<br> <br> |

What is the study measuring?
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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 |