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Due to the inclusion of an IMid in combination with pembrolizumab, Study Sponsor terminated the study.
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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This is an open label trial of Anti PD1/MD-3475, Pomalidomide and dexamethasone. The study will use standard (FDA approved) doses for both pomalidomide and dexamethasone. The experimental drug Anti PD-1 (MK 3475) given on days 1 and 14.
This phase I/II study is focused on patients with relapsed or refractory multiple myeloma. MK-3475 will be given as an intravenous infusion at every 2 weeks. Treatment will be administered on an outpatient basis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pomalidomide, Dexamethasone & MK-3475 | Experimental | Pomalidomide is given at standard dose of 4 mg daily orally for 21 days and dexamethasone is given at 40 mg orally weekly. MK3475 will be given as an intravenous infusion at 200 mg every 2 weeks (days 1 and 14). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-3475 | Drug | Anti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Participants With Adverse Events | Establish the safety and tolerability of Pomalidomide and Dexamethasone in combination with MK-3475 | 24 month |
| Measure | Description | Time Frame |
|---|---|---|
| PD-LI Expression On Myeloma Cells | The identification of a biomarker for response by evaluating PD-1/PDL-1 expression in patients' bone marrow aspirate samples will be analyzed in order to help select patients for future anti-PD-1 therapy. The main exploratory biomarker analysis was to examine potential correlation between expression of PD-1 on T cells and PD-L1 on myeloma cells with clinical outcome using the following parameters: response rate focusing on responses ≥ very good partial response (VGPR) and PFS. SAS software (v.9.4; SAS Institute, Inc, Cary, NC) was used for statistical analyses. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ashraf Z Badros, M.B.,Ch.B | University of Maryland Greenebaum Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore | Maryland | 21201-1592 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28461396 | Derived | Badros A, Hyjek E, Ma N, Lesokhin A, Dogan A, Rapoport AP, Kocoglu M, Lederer E, Philip S, Milliron T, Dell C, Goloubeva O, Singh Z. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Sep 7;130(10):1189-1197. doi: 10.1182/blood-2017-03-775122. Epub 2017 May 1. |
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Participants were recruited from the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center between December 2014 and May 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pomalidomide, Dexamethasone & MK-3475 | Pomalidomide is given at standard dose of 4 mg daily orally for 21 days and dexamethasone is given at 40 mg orally weekly. MK3475 will be given as an intravenous infusion at 200 mg every 2 weeks (days 1 and 14). MK-3475: Anti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks. Pomalidomide: Pomalidomide is given at standard dose of 4 mg daily orally for 21 days Dexamethasone: Dexamethasone is given at 40 mg orally weekly |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pomalidomide, Dexamethasone & MK-3475 | Pomalidomide is given at standard dose of 4 mg daily orally for 21 days and dexamethasone is given at 40 mg orally weekly. MK3475 will be given as an intravenous infusion at 200 mg every 2 weeks (days 1 and 14). MK-3475: Anti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks. Pomalidomide: Pomalidomide is given at standard dose of 4 mg daily orally for 21 days Dexamethasone: Dexamethasone is given at 40 mg orally weekly |
| 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 | The Number of Participants With Adverse Events | Establish the safety and tolerability of Pomalidomide and Dexamethasone in combination with MK-3475 | Posted | Count of Participants | Participants | 24 month |
|
Reported Adverse Events (AEs) include events starting on or after Day 0 and up to 30 days of receiving the last dose of study medication.
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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 | Pomalidomide, Dexamethasone & MK-3475 | Pomalidomide is given at standard dose of 4 mg daily orally for 21 days and dexamethasone is given at 40 mg orally weekly. MK3475 will be given as an intravenous infusion at 200 mg every 2 weeks (days 1 and 14). MK-3475: Anti PD-1 (MD 3475) will be given as an intravenous infusion at 200 mg every 2 weeks. Pomalidomide: Pomalidomide is given at standard dose of 4 mg daily orally for 21 days Dexamethasone: Dexamethasone is given at 40 mg orally weekly |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute coronary syndrome | Cardiac disorders | CTCAE 4.03 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| anemia | Blood and lymphatic system disorders | CTCAE 4.03 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ashraf Badros M.B.Ch.B | University of Maryland Greenebaum Comprehensive Cancer Center | 410-328-1230 | Abadros@umm.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 | Jul 7, 2017 | Sep 15, 2017 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| C467566 | pomalidomide |
| D003907 | Dexamethasone |
| D002123 | Calcium Dobesilate |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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| Pomalidomide | Drug | Pomalidomide is given at standard dose of 4 mg daily orally for 21 days |
|
|
| Dexamethasone | Drug | Dexamethasone is given at 40 mg orally weekly |
|
|
| Tissue sample collection will take place before starting study therapy with MK-3475 at baseline and again at time of relapse as defined by the International Myeloma Working Group Response Criteria (Average of up to 24months) |
| Time to Progression Free Survival (PFS) | PFS will be measured in all participants. Survival and PFS functions were estimated using the Kaplan-Meier method. The Cox regression model was used to assess the following plausible risk factors for OS and PFS: age, isotype, number of cycles of therapy, and cytogenetic profile. | PFS assessments will take place after starting study therapy with MD-3475 and will continue until the start of a new anti-neoplastic therapy, disease progression, death, or the end of study up to an average of 24 months. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | PD-LI Expression On Myeloma Cells | The identification of a biomarker for response by evaluating PD-1/PDL-1 expression in patients' bone marrow aspirate samples will be analyzed in order to help select patients for future anti-PD-1 therapy. The main exploratory biomarker analysis was to examine potential correlation between expression of PD-1 on T cells and PD-L1 on myeloma cells with clinical outcome using the following parameters: response rate focusing on responses ≥ very good partial response (VGPR) and PFS. SAS software (v.9.4; SAS Institute, Inc, Cary, NC) was used for statistical analyses. | Data were analyzed for 29 samples. | Posted | Count of Participants | Participants | Tissue sample collection will take place before starting study therapy with MK-3475 at baseline and again at time of relapse as defined by the International Myeloma Working Group Response Criteria (Average of up to 24months) |
|
|
|
| Secondary | Time to Progression Free Survival (PFS) | PFS will be measured in all participants. Survival and PFS functions were estimated using the Kaplan-Meier method. The Cox regression model was used to assess the following plausible risk factors for OS and PFS: age, isotype, number of cycles of therapy, and cytogenetic profile. | Posted | Median | 95% Confidence Interval | Months | PFS assessments will take place after starting study therapy with MD-3475 and will continue until the start of a new anti-neoplastic therapy, disease progression, death, or the end of study up to an average of 24 months. |
|
|
|
| 2 |
| 48 |
| 27 |
| 48 |
| 48 |
| 48 |
| heart failure | Cardiac disorders | CTCAE 4.03 | Systematic Assessment |
|
| cardiac arrest | Cardiac disorders | CTCAE 4.03 | Systematic Assessment |
|
| adrenal insufficiency | Endocrine disorders | CTCAE 4.03 | Systematic Assessment |
|
| colitis | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| lower gastrointestinal hemorrhage | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| fever | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| fracture | Injury, poisoning and procedural complications | CTCAE 4.03 | Systematic Assessment |
|
| hip fracture | Injury, poisoning and procedural complications | CTCAE 4.03 | Systematic Assessment |
|
| other, bacteremia | Infections and infestations | CTCAE 4.03 | Systematic Assessment |
|
| skin infection | Infections and infestations | CTCAE 4.03 | Systematic Assessment |
|
| alanine aminotransferase increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| alkaline phosphatase increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| creatinine increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| hyponatremia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| other, meniscus tear | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| other, breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE 4.03 | Systematic Assessment |
|
| intracranial hemorrhage | Nervous system disorders | CTCAE 4.03 | Systematic Assessment |
|
| syncope | Nervous system disorders | CTCAE 4.03 | Systematic Assessment |
|
| urinary retention | Renal and urinary disorders | CTCAE 4.03 | Systematic Assessment |
|
| bronchitis | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| lung infection | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| upper respiratory infection | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypotension | Vascular disorders | CTCAE 4.03 | Systematic Assessment |
|
| lymphocyte count decreased | Blood and lymphatic system disorders | CTCAE 4.03 | Systematic Assessment |
|
| neutrophil count decreased | Blood and lymphatic system disorders | CTCAE 4.03 | Systematic Assessment |
|
| platelet count decreased | Blood and lymphatic system disorders | CTCAE 4.03 | Systematic Assessment |
|
| white blood cell decreased | Blood and lymphatic system disorders | CTCAE 4.03 | Systematic Assessment |
|
| atrial fibrillation | Cardiac disorders | CTCAE 4.03 | Systematic Assessment |
|
| palpitations | Cardiac disorders | CTCAE 4.03 | Systematic Assessment |
|
| sinus tachycardia | Cardiac disorders | CTCAE 4.03 | Systematic Assessment |
|
| ear pain | Ear and labyrinth disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypothyroidism | Endocrine disorders | CTCAE 4.03 | Systematic Assessment |
|
| blurred vision | Eye disorders | CTCAE 4.03 | Systematic Assessment |
|
| abdominal pain | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| bloating | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| constipation | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| stomach pain | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| vomiting | Gastrointestinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| chest pain- non cardiac | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| chest pain- unspecified | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| chills | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| edema limbs | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| fatigue | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| fever | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| other, common cold | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| pain | General disorders | CTCAE 4.03 | Systematic Assessment |
|
| bruising | Injury, poisoning and procedural complications | CTCAE 4.03 | Systematic Assessment |
|
| fall | Injury, poisoning and procedural complications | CTCAE 4.03 | Systematic Assessment |
|
| fracture | Injury, poisoning and procedural complications | CTCAE 4.03 | Systematic Assessment |
|
| spinal fracture | Injury, poisoning and procedural complications | CTCAE 4.03 | Systematic Assessment |
|
| skin infection | Infections and infestations | CTCAE 4.03 | Systematic Assessment |
|
| urinary tract infection | Infections and infestations | CTCAE 4.03 | Systematic Assessment |
|
| activated partial thromboplastin time prolonged | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| alanine aminotransferase increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| alkaline phosphatase increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| aspartate aminotransferase increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| blood bilirubin increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| creatinine increased | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| weight gain | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| weight loss | Investigations | CTCAE 4.03 | Systematic Assessment |
|
| hypercalcemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hyperglycemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hyperkalemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypernatremia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hyperuricemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypoalbuminemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypocalcemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypoglycemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypokalemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypomagenesemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hyponatremia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypohosphatemia | Metabolism and nutrition disorders | CTCAE 4.03 | Systematic Assessment |
|
| arthralgia | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| arthritis | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| back pain | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| bone pain | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| chest wall pain | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| flank pain | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| other, muscle cramp | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| dizziness | Nervous system disorders | CTCAE 4.03 | Systematic Assessment |
|
| headache | Nervous system disorders | CTCAE 4.03 | Systematic Assessment |
|
| other, peripheral neuropathy NOS | Nervous system disorders | CTCAE 4.03 | Systematic Assessment |
|
| tremor | Nervous system disorders | CTCAE 4.03 | Systematic Assessment |
|
| anxiety | Psychiatric disorders | CTCAE 4.03 | Systematic Assessment |
|
| confusion | Psychiatric disorders | CTCAE 4.03 | Systematic Assessment |
|
| insomnia | Psychiatric disorders | CTCAE 4.03 | Systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| epitaxis | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| hiccups | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| lung infection | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| upper respiratory infection | Respiratory, thoracic and mediastinal disorders | CTCAE 4.03 | Systematic Assessment |
|
| hyperhidrosis | Skin and subcutaneous tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| other, rash unspecified | Skin and subcutaneous tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| pruritis | Skin and subcutaneous tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| rash maculopapular | Skin and subcutaneous tissue disorders | CTCAE 4.03 | Systematic Assessment |
|
| hot flashes | Vascular disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypertension | Vascular disorders | CTCAE 4.03 | Systematic Assessment |
|
| hypotension | Vascular disorders | CTCAE 4.03 | Systematic Assessment |
|
Not provided
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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 |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| Title | Measurements |
|---|---|
|