Hodgkin Disease, Lymphoma, Non-Hodgkin
Conditions
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
Interventions
DRUGCarmustine
DRUGEtoposide phosphate
DRUGCytarabine
DRUGMelphalan HCl (propylene glycol-free)
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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. .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 1 year | Percentage of patients who survive without any signs or symptoms of cancer at 1 year. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) |
|---|---|
| Age, Continuous | 51 years |
| Diagnosis Diffuse large B-cell lymphoma | 15 participants |
| Diagnosis Hodgkin lymphoma | 17 participants |
| Diagnosis Mantle cell lymphoma | 8 participants |
| Diagnosis Other Non-Hodgkin Lymphoma | 10 participants |
| Region of Enrollment United States | 50 participants |
| Remission status prior to autologous stem cell transplant Complete remission | 23 participants |
| Remission status prior to autologous stem cell transplant Partial remission | 25 participants |
| Remission status prior to autologous stem cell transplant Progressive disease | 2 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 50 |
| serious Total, serious adverse events | 1 / 50 |
Outcome results
Primary
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.
Time frame: Day -7 through Day 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Pain | 10 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Fever neutropenia | 34 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Fever | 6 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Bacteremia | 7 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Clostridium difficile | 3 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Respiratory infection | 5 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Mucosal infection | 7 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Skin infection | 3 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Genito-urinary tract infection | 3 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Hypotension | 15 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Abdominal pain | 5 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Diarrhea | 8 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Mucositis oral | 27 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Liver enzymes increased | 5 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Bilirubin increased | 5 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Dehydration | 5 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Hyperglycemia | 6 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Hypoalbuminemia | 10 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Hypocalcemia | 12 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Hypokalemia | 14 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Hypophosphatemia | 35 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Headache | 7 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Hypoxia | 9 participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events | Rash | 8 participants |
Primary
Treatment-related Mortality (TRM)
TRM is defined as death not due to progressive lymphoma prior to Day 100 after transplant
Time frame: 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Treatment-related Mortality (TRM) | 0 percentage of participants |
Secondary
Disease-free Survival
Percentage of patients who survive without any signs or symptoms of cancer at 1 year.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Disease-free Survival | 70 percentage of participants |
Secondary
Disease-free Survival
Percentage of patients who survive without any signs or symptoms of cancer at 2 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Disease-free Survival | 64 percentage of participants |
Secondary
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
Time frame: Up to Day 100
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Efficacy as Measured by Response Rates | Complete response | 84 percentage of participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Efficacy as Measured by Response Rates | Partial response | 4 percentage of participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Efficacy as Measured by Response Rates | Stable disease | 0 percentage of participants |
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Efficacy as Measured by Response Rates | Progressive disease | 12 percentage of participants |
Secondary
Time to Engraftment (Neutrophil)
Time from the date of the transplant to the date of neutrophil engraftment.
Time frame: Assessed up to day 30
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Time to Engraftment (Neutrophil) | 10 days |
Secondary
Time to Engraftment (Platelet)
Time from the date of transplant to the date of platelet engraftment.
Time frame: Assessed up to day 100
Population: One patient did not have platelet engraftment by Day 100
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Time to Engraftment (Platelet) | 19 days |
Post Hoc
Overall Survival (OS) Rate
Time frame: Median follow-up 15.4 months (range 4.7-24.6)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Overall Survival (OS) Rate | 10 percentage of participants |
Post Hoc
Progression-free Survival (PFS) Rate
PFS - Time from start of treatment to the time of progression or death, whichever occurs first.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Progression-free Survival (PFS) Rate | 84 percentage of participants |
Post Hoc
Progression-free Survival Rate (PFS)
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Progression-free Survival Rate (PFS) | 70 percentage of participants |
Post Hoc
Relapse Free Survival
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | Relapse Free Survival | 0 percentage of participants |