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| ID | Type | Description | Link |
|---|---|---|---|
| NA_00084466 | Other Identifier | JHMIRB |
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| Name | Class |
|---|---|
| The Leukemia and Lymphoma Society | OTHER |
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This research is being done to find out if altering the immune system by giving activated marrow infiltrating lymphocytes (MILs) can improve outcomes for multiple myeloma patients who receive a standard autologous stem cell transplant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| aMIL Arm | Experimental | Patients receive activated Marrow Infiltrating Lymphocytes (aMIL) |
|
| No aMIL | Active Comparator | Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| aMIL | Biological | On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Feasibility is defined as the ability to harvest, expand, and infuse the MILs product within 120 days. After treating 60 patients with MILs, we will declare MILs not feasible if we can only harvest, expand, and deliver MILs to 40 or fewer patients. | 120 days |
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events | Total number of adverse events grade 3 or higher that occur from MILs harvest through 60 days after transplant. | 60 days from aMILs harvest until day 60 after transplant |
| Overall Survival (OS) |
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Inclusion Criteria:
Exclusion Criteria:
Diagnosis of any of the following cancers:
Diagnosis of amyloidosis;
Failed to achieve at least a partial response (PR) to latest therapy;
Previous hematopoietic stem cell transplantation;Patients can have had prior relapsed disease as long as they have never been previously transplanted;
Known history of HIV infection;
Use of corticosteroids (glucocorticoids) within 21 days of bone marrow collection;
Use of any myeloma-specific therapy within 21 days of bone marrow collection;
Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of registration;
Participation in any clinical trial within 28 days of registration on this trial, which involved an investigational drug or device;
History of malignancy other than multiple myeloma within five years of registration, except adequately treated basal or squamous cell skin cancer;
Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring active systemic treatment. Hypothyroidism without evidence of Grave's disease or Hashimoto's thyroiditis is permitted.
Human T-lymphotropic virus (HTLV) 1 or 2 positive;
Known hypersensitivity to Prevnar or any of its components;
Contraindication to phosphodiesterase-5 inhibitors (e.g. currently on nitrates).
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| Name | Affiliation | Role |
|---|---|---|
| Philip Imus, M.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231 | United States |
Of the 102 patients randomized, one was randomized to the control group who was lost to follow-up prior to start; did not have aMILs harvested, and was not transplanted. This patient is therefore not included in this report.
Participants were enrolled at four sites: Johns Hopkins University, Moffitt Cancer Center, Mayo Clinic (Jacksonville) and the Blood and Marrow Transplant Group of Georgia (Northside).
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| ID | Title | Description |
|---|---|---|
| FG000 | aMIL Arm | Patients receive activated Marrow Infiltrating Lymphocytes (aMIL) aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide. |
| FG001 | No aMIL | Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL) No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | aMIL Arm | Patients receive activated Marrow Infiltrating Lymphocytes (aMIL) aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide. |
| BG001 | No aMIL |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Feasibility is defined as the ability to harvest, expand, and infuse the MILs product within 120 days. After treating 60 patients with MILs, we will declare MILs not feasible if we can only harvest, expand, and deliver MILs to 40 or fewer patients. | 71 patients were evaluable in the feasibility set: 70 randomized to the aMILs Arm, plus one patient who was not randomized due to harvest failure. | Posted | Count of Participants | Participants | 120 days |
|
60 Days from aMILs harvest until Day 60 after transplant
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | aMIL Arm | Patients receive activated Marrow Infiltrating Lymphocytes (aMIL) aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher Adverse Events (AEs) from aMILs harvest to 60 days following autologous stem cell transplant (ASCT) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| manufacture failure | Product Issues | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Philip Imus, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | 410-955-8873 | pimus1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 15, 2020 | Jun 5, 2020 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| No aMIL | Drug | On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide. |
|
OS assessed by number of participants alive at the end of follow up period. |
| 3 years |
| Progression-free Survival (PFS) | Median PFS time equals the time of randomization (in months) until disease progression, death from any cause, or protocol deviation due to lenalidomide dosing (above 10mg), whichever occurs first. | 5 years |
| Disease progression |
|
| Product contamination |
|
| Failed expansion of cell product |
|
Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)
No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Disease Status | Count of Participants | Participants |
|
| Myeloma Prognostic Risk Signature (MYPRS) Risk Category | The Myeloma Prognostic Risk Signature (MyPRS®) (Signal Genetics™) is used to estimate the underlying activity of disease progression in patients diagnosed with active multiple myeloma. | Count of Participants | Participants |
|
| 70-gene expression Prognostic Risk Score (GEP-70) | The 70-gene Prognostic Risk Score (GEP-70) quantifies the expression of 70 genes commonly altered in multiple myeloma. Primarily prognostic, GEP-70 assesses risk of disease relapse and survival outcomes and is the randomization stratification of the MYPRS multiple myeloma specific gene expression profile risk categories. | Count of Participants | Participants |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status | ECOG Scoring System 0= Fully active, able to carry on all pre-disease performance without restriction
| Count of Participants | Participants |
|
| International Staging System (ISS) Multiple Myeloma Classification | Prognosticates the severity of multiple myeloma and patient survival based on routinely obtained lab values. Stage I= Serum β2 microglobulin < 3.5 mg/l; serum albumin ≥ 3.5 g/dl; standard-risk chromosomal abnormalities (CA) and normal lactate dehydrogenase (LDH) Stage II= not stage I or Stage III Stage III= Serum β2 microglobulin ≥ 5.5 mg/L and either high-risk CA by florescent in situ hybridization (FISH) or high LDH | Count of Participants | Participants |
|
| Salmon Stage multiple myeloma classification | demonstrates the correlation between the amount of myeloma and the damage it has caused based on number of bone lesions, anemia, serum calcium levels, and serum and urine light chain levels, and can be measured as myeloma cell mass (myeloma cells in billions/m2)* . Stage I= low cell mass (600 billion) Stage II= intermediate cell mass (600-1200 billion) Stage III= high cell mass (>1200 billion) Subcategory: A = normal renal function. B= abnormal renal function | Count of Participants | Participants |
|
| Number of Prior Multiple Myeloma Treatments | Median | Inter-Quartile Range | prior treatments |
|
| Time to Diagnosis | Median | Inter-Quartile Range | years |
|
| Time to stem cell transplant (SCT) | Median | Inter-Quartile Range | Days |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events | Total number of adverse events grade 3 or higher that occur from MILs harvest through 60 days after transplant. | Posted | Number | adverse events | 60 days from aMILs harvest until day 60 after transplant |
|
|
|
| Secondary | Overall Survival (OS) | OS assessed by number of participants alive at the end of follow up period. | This is an analysis by intention-to-treat and only considers transplanted patients randomized to the aMILs arm. | Posted | Count of Participants | Participants | 3 years |
|
|
|
| Secondary | Progression-free Survival (PFS) | Median PFS time equals the time of randomization (in months) until disease progression, death from any cause, or protocol deviation due to lenalidomide dosing (above 10mg), whichever occurs first. | This is an analysis by intention-to-treat and only considers transplanted patients randomized to the aMILs arm. | Posted | Median | Inter-Quartile Range | months | 5 years |
|
|
|
| 1 |
| 70 |
| 64 |
| 70 |
| 11 |
| 70 |
| EG001 | No aMIL | Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL) No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide. | 1 | 31 | 29 | 31 | 0 | 31 |
|
| Acute Kidney Injury | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| Atrial Fibrillation | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| Back Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Pancytopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Bone Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Colitis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Device related infection | Injury, poisoning and procedural complications | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Enterocolitis infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Esophagitis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| fever | General disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Gastric ulcer | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| hypotension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| bacteremia | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| Kidney infection | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| lung infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| lymphocyte count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| mucosal infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| neutrophil count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| platelet count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| renal calculi | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| Scrotal Infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| Stroke | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| syncope | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| thromboembolic event | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| upper respiratory infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| ventricular arrhythmia | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
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| vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 or higher AEs from aMILs harvest to 60 days following ASCT |
|
| white blood cell decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| product contamination | Product Issues | CTCAE (4.0) | Non-systematic Assessment |
|
| infusion related reaction | General disorders | CTCAE (4.0) | Non-systematic Assessment | 63 participants in the aMILs Arm had infusions, of those, 8 had record of infusion reaction. |
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| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |