A Study of Granix to Disrupt the Bone Marrow Microenvironment in Patients With Multiple Myeloma Undergoing Autologous Transplantation

Study Overview
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Brief Summary
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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

Official Title
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A Study of Granix to Disrupt the Bone Marrow Microenvironment in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Granix
* Drug: High dose melphalan (HDR)
* Procedure: Autologous Stem Cell Transplant (ASCT)


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Granix and high dose melphalan (HDM)<br>Granix on Day -7 through Day -2. HDM intravenously (IV) on Day -2. Autologous stem cell transplantation on Day 0 | Drug: Granix<br> <br> * Other names: XM02 filgrastim;Drug: High dose melphalan (HDR)<br> <br> * Other names: Phenylalanine mustard;Procedure: Autologous Stem Cell Transplant (ASCT)<br> <br> |
| Active Comparator: Control: High dose melphalan (HDM)<br>HDM intravenously (IV) on Day -2. Autologous stem cell transplantation on Day 0. | Drug: High dose melphalan (HDR)<br> <br> * Other names: Phenylalanine mustard;Procedure: Autologous Stem Cell Transplant (ASCT)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Day +100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | -Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | Up through Day 30 | 
| 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 | Up to 2 years | 
| 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. | Up to 2 years | 
| 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 | Up to 2 years | 
| 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. | Up to Day 30 | 
| 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. | Up to Day 100 |