Multiple Myeloma
Conditions
Brief summary
This randomized phase II trial compares how well adding XMO2 Filgrastim (Granix) to melphalan before a stem cell transplant works in treating patients with multiple myeloma. Chemotherapy drugs, such as melphalan, are given to prepare the bone marrow for the stem cell transplant. Giving colony-stimulating factors, such as XMO2 Filgrastim (Granix), may help multiple myeloma cells move from the patient's bone marrow to the blood where they may be more sensitive to treatment with melphalan. It is not yet known whether adding XMO2 Filgrastim (Granix) to melphalan before a stem cell transplant will work better than melphalan alone in treating multiple myeloma
Interventions
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Symptomatic multiple myeloma requiring treatment * Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy * At least 18 years of age * Adequate autologous stem cell collection, defined as an unmanipulated, cryopreserved, peripheral blood stem cell collection containing at least 2 × 10\^6 CD34+ cells/kg based on patient body weight. * Adequate organ function as measured by: * Cardiac function: Left ventricular ejection fraction at rest ≥40% * Hepatic function: Bilirubin ≤2 × ULN and aspartate amino transferase/alanine amino transferase (AST/ALT) ≤3 × ULN * Renal function: Creatinine clearance ≥40 mL/minute (measured or calculated/estimated) * Pulmonary function: Carbon monoxide diffusing capacity (DLCO; corrected for hemoglobin \[Hgb\]), forced expiratory volume in 1 second (FEV1), forced expiratory vital capacity (FVC) ≥50% of predicted value * Oxygen saturation ≥92% on room air * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. * Able to understand and willing to sign an IRB-approved written informed consent document
Exclusion criteria
* Evidence of multiple myeloma disease progression (as defined by IMWG) any time prior to ASCT * Prior stem cell transplant (autologous or allogeneic) * Smoldering MM not requiring therapy * Plasma cell leukemia * Systemic amyloid light chain amyloidosis * Active bacterial, viral, or fungal infection * Seropositive for human immunodeficiency virus (HIV) * Known, active hepatitis A, B, or C Infection * Pregnant or breastfeeding. * Receiving other concurrent anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy, but excluding corticosteroids) within 7 days prior to the ASCT or planning to receive any of these treatments prior to the last study visit on Day +100. * Hypersensitive or intolerant to any component of the study drug(s) formulation * Receiving growth factors (filgrastim, XM02-filgrastim, peg-filgrastim, plerixafor, etc) or undergoing apheresis \< 14 days prior to the start of treatment on protocol (Day -7).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response or Stringent Complete Response | Day +100 | Complete response (CR) requires all of the following: * Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine * \<5% plasma cells in the bone marrow * Disappearance of soft tissue plasmacytomas Stringent complete response (sCR) requires all of the following: * CR as defined above * Normal free light chain ratio * Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response | Up to 2 years | Overall response rate=CR+sCR+VGPR+PR Complete response (CR), disappearance of monoclonal protein from the blood & urine and \<5% plasma cells in bone marrow &disappearance of soft tissue plasmacytomas Stringent complete response (sCR), CR & normal free light chain ratio & absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence Very good partial response (VGPR), serum and urine monoclonal protein detectable by immunofixation but not on electrophoresis OR \> 90% reduction in serum monoclonal protein with urine monoclonal protein \< 100 mg per 24 hours and if present, \> 50% reduction in the size of soft tissue plasmacytomas Partial response (PR), \> 50% reduction in the level of the serum monoclonal protein & reduction in urine monoclonal protein & \> 50% reduction in the size of soft tissue plasmacytomas & if serum and urine monoclonal protein are unmeasurable and serum free light chain is unmeasurable, a \> 50% reduction in plasma cells is required |
| Overall Survival as Measured by Number of Participants Alive at Last Follow-up | Up to 2 years | OS is defined as the duration from the time of transplant Day 0 to death or last follow-up. |
| Number of Participants With Adverse Events | Up through Day 30 | -Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |
| Number of Participants With Neutrophil Engraftment | Up to Day 30 | Neutrophil engraftment is defined as ANC ≥ 0.5 × 10\^9/L × 3 consecutive daily assessments. The first of 3 consecutive days for which ANC ≥ 0.5 × 109/L will be recorded as the date of neutrophil engraftment. Time to neutrophil engraftment will be calculated as the time from the date of the ASCT to the date of neutrophil engraftment. |
| Number of Participants With Platelet Engraftment | Up to Day 100 | Platelet engraftment is defined as an untransfused platelet measurement \>20,000/mm3 × 3 consecutive daily assessments. The first of 3 consecutive days for which the untransfused platelet measurement is \>20,000/mm3 will be recorded as the date of platelet engraftment. Time to platelet engraftment will be calculated as the time from receiving the date of ASCT to the date of platelet engraftment. Untransfused is defined as no transfusions within 7 days. |
| Progression-free Survival as Measured by Number of Participants Without Disease Progression at Last Follow-up | Up to 2 years | PFS is defined as the duration from time of transplant Day 0 to time of first progression/clinical relapse, death, or the date the patient was last known to be in remission |
Countries
United States
Participant flow
Recruitment details
The study opened to participant enrollment on 01/20/2015 and closed to participant enrollment on 07/03/2018.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) Granix on Day -7 through Day -2.
HDM intravenously (IV) on Day -2.
Autologous stem cell transplantation on Day 0 | 45 |
| Control: High Dose Melphalan (HDM) HDM intravenously (IV) on Day -2. | 45 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Experimental: Granix and High Dose Melphalan (HDM) | Total | Control: High Dose Melphalan (HDM) |
|---|---|---|---|
| Age, Continuous | 57 years | 59.5 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 89 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 11 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 79 Participants | 38 Participants |
| Region of Enrollment United States | 45 Participants | 90 Participants | 45 Participants |
| Sex: Female, Male Female | 18 Participants | 43 Participants | 25 Participants |
| Sex: Female, Male Male | 27 Participants | 47 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 45 | 43 / 45 |
| other Total, other adverse events | 45 / 45 | 45 / 45 |
| serious Total, serious adverse events | 10 / 45 | 4 / 45 |
Outcome results
Primary
Number of Participants With Complete Response or Stringent Complete Response
Complete response (CR) requires all of the following: * Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine * \<5% plasma cells in the bone marrow * Disappearance of soft tissue plasmacytomas Stringent complete response (sCR) requires all of the following: * CR as defined above * Normal free light chain ratio * Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence
Time frame: Day +100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Complete Response or Stringent Complete Response | 17 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Complete Response or Stringent Complete Response | 17 Participants |
Secondary
Number of Participants With Adverse Events
-Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: Up through Day 30
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Nausea | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypocalcemia | 25 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Syncope | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypokalemia | 16 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Oral pain | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hyponatremia | 4 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Left ventricular systolic function | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypophosphatemia | 40 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Upper gastrointestinal hemorrhage | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bone pain | 4 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Supraventricular tachycardia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Muscle cramps-back/legs | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Edema limbs | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Right thigh/leg pain | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Sinus tachycardia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Acitinic Keratosis (right shoulder) | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Fever | 5 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Headache | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary tract pain | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Infusion related reaction | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Tremor | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Excessive cerumen | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Anxiety | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Malaise | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypertension | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Upper respiratory infection | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pain | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary tract infection | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Impacted cerumen | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Vaginal infection | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Fall | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bleeding from CVC insertion site | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Delirium | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Allergic reaction | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Insomnia | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Adrenal insufficiency | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hematuria | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia-Coagulase negative staphyococcus | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Proteinuria | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dry eye | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Cough | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Enterobacter Clocae | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dyspnea | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pneumonitis | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypoxia | 8 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Fusobacterium | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pleural effusion | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Abdominal pain | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pulmonary edema | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - MSSA | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Wheezing | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Myocardial infarction | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Erythematous nodules | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Pseudomonas Aeruginosa | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pruritus | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Colitis | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rash acneiform | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Streptococcus mitis | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rash maculo-papular | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Productive cough | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Skin lesion | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Candida (groin) | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Flushing | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Colonic perforation | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypotension | 5 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Clostridium difficile | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Phlebitis | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | SIADH | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Thromboembolic event | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Lung infection | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Atrial flutter | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Constipation | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hemorrhoidal hemorrhage | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Mucosal infection (oral thrush) | 10 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Odynophagia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rash forehead/back | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Chills | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Peri-rectal yeast infection | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Multi-organ failure | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Diarrhea | 5 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Non-cardiac chest pain | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Sepsis | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Gram Positive | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hematoma | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia-Serratia liquefaciens/pantoea species | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Skin infection | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Catheter related infection | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Enterocolitis | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | CMV viremia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Splenic infection | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Esophageal infection | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Skin ulceration | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Otitis media | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Activated partial thromboplastin time prolonged | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rhinitis infective | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Epigastric pain | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Alanine aminotransferase increased | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Aspartate aminotransferase increased | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Alkaline phosphatase increased | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dyspepsia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | INR increased | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Blood bilirubin increased | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hyperglycemia | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Reversible posterior leukoencephalopathy syndrome | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Uncontrolled Diabetes Mellitus | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Esophagitis | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Generalized muscle weakness | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Creatinine increased | 4 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Jaw pain | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Palpitations | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Joint effusion | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Electrocardiogram QT corrected interval prolonged | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Encephalopathy | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hemorrhoids | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Peripheral sensory neuropathy | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Weight loss | 6 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Presyncope | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Febrile neutropenia | 30 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Acute kidney injury | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Anorexia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary frequency | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Ileus | 0 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary retention | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Scrotal pain | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dehydration | 6 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Atelectasis | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dysphagia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Epistaxis | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypernatremia | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hiccups | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Mucositis oral | 16 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Respiratory failure | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hyperuricemia | 2 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Sore throat | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Atrial fibrillation | 3 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Facial rash/dermatitis | 1 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypoalbuminemia | 18 Participants |
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Follicular rash-back/posterior neck | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hyperglycemia | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Reversible posterior leukoencephalopathy syndrome | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Flushing | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hematoma | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Myocardial infarction | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Palpitations | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Supraventricular tachycardia | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Adrenal insufficiency | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | SIADH | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dyspepsia | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dysphagia | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary retention | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary tract pain | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hiccups | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pneumonitis | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Follicular rash-back/posterior neck | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rash forehead/back | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Skin ulceration | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bleeding from CVC insertion site | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Febrile neutropenia | 27 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Atrial fibrillation | 2 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Left ventricular systolic function | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Sinus tachycardia | 3 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Excessive cerumen | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Impacted cerumen | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dry eye | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Abdominal pain | 2 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Colitis | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Colonic perforation | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Constipation | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Diarrhea | 11 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Enterocolitis | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Epigastric pain | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Esophagitis | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hemorrhoids | 2 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Ileus | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Mucositis oral | 14 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Nausea | 5 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Oral pain | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Upper gastrointestinal hemorrhage | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Edema limbs | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Fever | 4 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Infusion related reaction | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Malaise | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pain | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Allergic reaction | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia-Coagulase negative staphyococcus | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Enterobacter Clocae | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Fusobacterium | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - MSSA | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Pseudomonas Aeruginosa | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Streptococcus mitis | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Candida (groin) | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Clostridium difficile | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Lung infection | 3 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Mucosal infection (oral thrush) | 11 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Peri-rectal yeast infection | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Sepsis | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Skin infection | 3 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Fall | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Activated partial thromboplastin time prolonged | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Aspartate aminotransferase increased | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Blood bilirubin increased | 2 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Creatinine increased | 3 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Electrocardiogram QT corrected interval prolonged | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Weight loss | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Anorexia | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dehydration | 3 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypernatremia | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hyperuricemia | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypoalbuminemia | 20 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypocalcemia | 22 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypokalemia | 16 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hyponatremia | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypophosphatemia | 35 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bone pain | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Muscle cramps-back/legs | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Right thigh/leg pain | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Acitinic Keratosis (right shoulder) | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Headache | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Syncope | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Tremor | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Anxiety | 2 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Splenic infection | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Upper respiratory infection | 4 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary tract infection | 4 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Vaginal infection | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Delirium | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Insomnia | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hematuria | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Proteinuria | 2 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Cough | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Dyspnea | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypoxia | 5 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pleural effusion | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pulmonary edema | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Wheezing | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Erythematous nodules | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Pruritus | 2 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rash acneiform | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rash maculo-papular | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Skin lesion | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypertension | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hypotension | 12 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Phlebitis | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Thromboembolic event | 1 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Atrial flutter | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Hemorrhoidal hemorrhage | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Odynophagia | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Chills | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Multi-organ failure | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Non-cardiac chest pain | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia - Gram Positive | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Bacteremia-Serratia liquefaciens/pantoea species | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Catheter related infection | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | CMV viremia | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Esophageal infection | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Otitis media | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Rhinitis infective | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Alanine aminotransferase increased | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Alkaline phosphatase increased | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | INR increased | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Uncontrolled Diabetes Mellitus | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Generalized muscle weakness | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Jaw pain | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Joint effusion | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Encephalopathy | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Peripheral sensory neuropathy | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Presyncope | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Acute kidney injury | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Urinary frequency | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Scrotal pain | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Atelectasis | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Epistaxis | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Productive cough | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Respiratory failure | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Sore throat | 0 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Adverse Events | Facial rash/dermatitis | 0 Participants |
Secondary
Number of Participants With Neutrophil Engraftment
Neutrophil engraftment is defined as ANC ≥ 0.5 × 10\^9/L × 3 consecutive daily assessments. The first of 3 consecutive days for which ANC ≥ 0.5 × 109/L will be recorded as the date of neutrophil engraftment. Time to neutrophil engraftment will be calculated as the time from the date of the ASCT to the date of neutrophil engraftment.
Time frame: Up to Day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Neutrophil Engraftment | 44 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Neutrophil Engraftment | 45 Participants |
Secondary
Number of Participants With Overall Response
Overall response rate=CR+sCR+VGPR+PR Complete response (CR), disappearance of monoclonal protein from the blood & urine and \<5% plasma cells in bone marrow &disappearance of soft tissue plasmacytomas Stringent complete response (sCR), CR & normal free light chain ratio & absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence Very good partial response (VGPR), serum and urine monoclonal protein detectable by immunofixation but not on electrophoresis OR \> 90% reduction in serum monoclonal protein with urine monoclonal protein \< 100 mg per 24 hours and if present, \> 50% reduction in the size of soft tissue plasmacytomas Partial response (PR), \> 50% reduction in the level of the serum monoclonal protein & reduction in urine monoclonal protein & \> 50% reduction in the size of soft tissue plasmacytomas & if serum and urine monoclonal protein are unmeasurable and serum free light chain is unmeasurable, a \> 50% reduction in plasma cells is required
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Overall Response | 41 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Overall Response | 42 Participants |
Secondary
Number of Participants With Platelet Engraftment
Platelet engraftment is defined as an untransfused platelet measurement \>20,000/mm3 × 3 consecutive daily assessments. The first of 3 consecutive days for which the untransfused platelet measurement is \>20,000/mm3 will be recorded as the date of platelet engraftment. Time to platelet engraftment will be calculated as the time from receiving the date of ASCT to the date of platelet engraftment. Untransfused is defined as no transfusions within 7 days.
Time frame: Up to Day 100
Population: 1 participant in control arm did not have a decrease in platelets and is not evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) | Number of Participants With Platelet Engraftment | 44 Participants |
| Control: High Dose Melphalan (HDM) | Number of Participants With Platelet Engraftment | 44 Participants |
Secondary
Overall Survival as Measured by Number of Participants Alive at Last Follow-up
OS is defined as the duration from the time of transplant Day 0 to death or last follow-up.
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) | Overall Survival as Measured by Number of Participants Alive at Last Follow-up | 40 Participants |
| Control: High Dose Melphalan (HDM) | Overall Survival as Measured by Number of Participants Alive at Last Follow-up | 43 Participants |
p-value: 0.43Log Rank
Secondary
Progression-free Survival as Measured by Number of Participants Without Disease Progression at Last Follow-up
PFS is defined as the duration from time of transplant Day 0 to time of first progression/clinical relapse, death, or the date the patient was last known to be in remission
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Granix and High Dose Melphalan (HDM) | Progression-free Survival as Measured by Number of Participants Without Disease Progression at Last Follow-up | 37 Participants |
| Control: High Dose Melphalan (HDM) | Progression-free Survival as Measured by Number of Participants Without Disease Progression at Last Follow-up | 36 Participants |
p-value: 0.6Log Rank