Multiple Myeloma, Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
Brief summary
RATIONALE: Drugs used in chemotherapy such as dexamethasone use different ways to stop cancer cells from dividing so they stop growing or die. Lenalidomide may stop the growth of multiple myeloma by stopping blood flow to the tumor. It is not yet known whether dexamethasone is more effective with or without lenalidomide in treating multiple myeloma. PURPOSE: This randomized phase III trial is studying dexamethasone and lenalidomide to see how well they work compared to dexamethasone alone in treating patients with previously untreated stage I, stage II, or stage III multiple myeloma.
Detailed description
OBJECTIVES: * Compare the progression-free survival of patients with previously untreated stage I, II, or III multiple myeloma treated with dexamethasone with or without lenalidomide. * Compare the overall response rate in patients treated with these regimens. * Compare the major response rate (indicated by greater than 75% decrease in M-protein) in patients treated with these regimens. * Compare the overall survival and time to best response in patients treated with these regimens. * Compare the toxicity profile of these regimens, including thrombotic complications, in these patients. * Compare the effect of these regimens on gene expression and proteomic analysis in these patients. OUTLINE: This is a randomized, double-blind, crossover, multicenter study. Patients are stratified according to disease stage by the International Staging System (I vs II vs III) and Zubrod performance status (0-1 vs 2-3). Patients are randomized to 1 of 2 treatment arms. Arm I * Induction therapy: Patients receive oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. * Maintenance therapy: Patients receive oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II * Induction therapy: Patients receive DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Patients with responding or stable disease proceed to maintenance therapy. Patients with disease progression during induction therapy cross over and receive unblinded treatment with DM and lenalidomide as in arm I induction. Patients with responding or stable disease after unblinded induction therapy receive unblinded maintenance therapy with DM and lenalidomide as in arm I maintenance. * Maintenance therapy: Patients receive oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance. Patients with disease progression during maintenance therapy cross over and receive unblinded treatment with DM and lenalidomide as in arm I induction. Patients with responding or stable disease after unblinded induction therapy proceed to unblinded maintenance therapy with DM and lenalidomide as in arm I maintenance. Patients are followed periodically for up to 5 years. PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this study within 4 years.
Interventions
DRUGdexamethasone
Given orally
DRUGlenalidomide
Given orally
OTHERplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Previously untreated multiple myeloma * Stage I, II, or III disease by the International Staging System * Measurable M-protein as defined by 1 of the following: * Serum M-protein at least 1.0 g/dL by serum protein electrophoresis or immunoelectrophoresis * Urinary M-protein excretion at least 200 mg/24 hours * No nonsecretory multiple myeloma * Not planning to undergo future autologous stem cell transplantation PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-3\* NOTE: \*Zubrod 3 allowed only if multiple myeloma is the central cause of disability Life expectancy * Not specified Hematopoietic * Platelet count at least 80,000/mm\^3\* * Absolute neutrophil count at least 1,000/mm\^3\* * Hemoglobin at least 9 g/dL\* (epoetin alfa or transfusion allowed) NOTE: \*Unless due to greater than 50% marrow involvement by myeloma on biopsy Hepatic * AST/ALT no greater than 3 times upper limit of normal\* NOTE: \*Values outside of this range are allowed at the investigator's discretion Renal * Creatinine no greater than 2.5 mg/dL\* NOTE: \*Values outside of this range are allowed at the investigator's discretion Cardiovascular * No New York Heart Association class III or IV heart failure * No myocardial infarction within the past 6 months * No poorly controlled hypertension Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment * Female patients must use 2 reliable forms of contraception simultaneously * Male patients must use effective barrier contraception * No uncontrolled active infection requiring IV antibiotics * No poorly controlled diabetes mellitus that would preclude ability to take oral glucocorticoids * No other serious medical condition that would preclude study participation * No psychiatric illness that would preclude study participation * No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * Must be able to take aspirin by mouth at a dose of 325 mg per day or enoxaparin subcutaneously at a dose of 40 mg per day as a form of thrombotic prophylaxis, except if already on therapeutic anticoagulant medication PRIOR CONCURRENT THERAPY: Biologic therapy * No prior interferon or thalidomide Chemotherapy * No prior chemotherapy Endocrine therapy * Prior high-dose dexamethasone allowed provided duration of administration was no more than 4 days Radiotherapy * Prior localized radiotherapy allowed provided it was not to the sole site of evaluable disease Surgery * Not specified Other * No prior treatment for clinically significant ventricular cardiac arrhythmias * Concurrent bisphosphonates allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years | Progression is defined as a \> 25% increase from baseline in myeloma protein production or other signs of disease progression such as hypercalcemia, etc. In patients with a confirmed Partial Remission, Remission, or Complete Remission, relapse is defined as the first occurrence of any of the following: 1) a myeloma protein increase by than 100% from the lowest level recorded on study, provided the absolute magnitude of this increase is at least 1g/dL for a serum monoclonal protein or at least 500 mg/24 hrs of urine M-protein; 2) a myeloma protein increase above the response criteria for Partial Remission, with the same requirements for the absolute magnitude of the protein increase; 3)reappearance of any myeloma peak that had disappeared while on protocol treatment, provided it meets the same requirements listed above; 4) increase in the size and number of lytic bone lesions recognized on radiographs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | From time of initiating study treatment until discontinuation of study treatment or of open-label REVLIMID + LOW DOSE DEX, whichever comes last, up to 5 years | Compare the toxicity profile of these regimens, including thrombotic complications, in these patients, based on CTCAE v. 3.0. |
Countries
United States
Participant flow
Recruitment details
Between October 15, 2004 and April 2, 2007, 198 patients were enrolled at 41 cooperative medical institutions.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide+Dexamethasone Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 97 |
| Dexamethasone Patients receive induction therapy comprising DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Some patients may then receive maintenance therapy comprising oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance. | 95 |
| Total | 192 |
Baseline characteristics
| Characteristic | Lenalidomide+Dexamethasone | Dexamethasone | Total |
|---|---|---|---|
| Age, Continuous Overall | 64.9 years | 63.1 years | 64.6 years |
| Sex: Female, Male Female | 44 Participants | 40 Participants | 84 Participants |
| Sex: Female, Male Male | 53 Participants | 55 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 91 / 96 | 90 / 94 | 39 / 40 |
| serious Total, serious adverse events | 41 / 96 | 21 / 94 | 14 / 40 |
Outcome results
Primary
Progression-Free Survival
Progression is defined as a \> 25% increase from baseline in myeloma protein production or other signs of disease progression such as hypercalcemia, etc. In patients with a confirmed Partial Remission, Remission, or Complete Remission, relapse is defined as the first occurrence of any of the following: 1) a myeloma protein increase by than 100% from the lowest level recorded on study, provided the absolute magnitude of this increase is at least 1g/dL for a serum monoclonal protein or at least 500 mg/24 hrs of urine M-protein; 2) a myeloma protein increase above the response criteria for Partial Remission, with the same requirements for the absolute magnitude of the protein increase; 3)reappearance of any myeloma peak that had disappeared while on protocol treatment, provided it meets the same requirements listed above; 4) increase in the size and number of lytic bone lesions recognized on radiographs.
Time frame: From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenalidomide and Dexamethasone | Progression-Free Survival | 78 percentage of participants |
| Dexamethasone | Progression-Free Survival | 52 percentage of participants |
Secondary
Toxicity
Compare the toxicity profile of these regimens, including thrombotic complications, in these patients, based on CTCAE v. 3.0.
Time frame: From time of initiating study treatment until discontinuation of study treatment or of open-label REVLIMID + LOW DOSE DEX, whichever comes last, up to 5 years
Population: All participants receiving at least one dose of induction therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide and Dexamethasone | Toxicity | Rash: acne/acneiform | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Gastrointestinal-Other (Specify) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Joint | 3 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Dizziness | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Glomerular filtration rate | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pneumonitis/pulmonary infiltrates | 3 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Arthritis (non-septic) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Glucose, serum-high (hyperglycemia) | 5 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Ophthalmoplegia/diplopia (double vision) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Weight loss | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Glucose, serum-low (hypoglycemia) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Dehydration | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Heartburn/dyspepsia | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Potassium, serum-low (hypokalemia) | 6 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Aspiration | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Hemoglobin | 6 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Muscle | 3 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Hemorrhage, CNS | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Prolonged QTc interval | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Ocular/Visual-Other (Specify) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Hemorrhage, GI - Colon | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Dyspnea (shortness of breath) | 4 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Ataxia (incoordination) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Hypertension | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Proteinuria | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Bladder | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Hypotension | 3 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Pain NOS | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Gastritis (including bile reflux gastritis) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Hypoxia | 4 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 21 Participants |
| Lenalidomide and Dexamethasone | Toxicity | INR (of prothrombin time) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | PTT (Partial thromboplastin time) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Encephalopathy | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Rash/desquamation | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Wound | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Stomach | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | 5 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Anorexia | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | CNS cerebrovascular ischemia | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Up aerodigest | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Rash: erythema multiforme | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | AST, SGOT | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Fatigue (asthenia, lethargy, malaise) | 19 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Mood alteration - anxiety | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bladder | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Renal failure | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Calcium, serum-high (hypercalcemia) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Dermatology/Skin-Other (Specify) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain-Other (Specify) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Colon | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Bone | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | SVT and nodal arrhythmia - Atrial fibrillation | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Constipation | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Up airway | 3 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pancreatic endocrine: glucose intolerance | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Calcium, serum-low (hypocalcemia) | 7 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Sodium, serum-high (hypernatremia) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Cystitis | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-cran | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Febrile neutropenia | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Sodium, serum-low (hyponatremia) | 3 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Infection with unknown ANC - Lung (pneumonia) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Extremity-limb | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Cardiopulmonary arrest, cause unknown (non-fatal) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Infection with unknown ANC - Upper airway NOS | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Mood alteration - depression | 11 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Somnolence/depressed level of consciousness | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Infection-Other (Specify) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Perforation, GI - Colon | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Syncope (fainting) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Insomnia | 4 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Abdomen NOS | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Cataract | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Joint-function | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Speech impairment (e.g., dysphasia or aphasia) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Albumin, serum-low (hypoalbuminemia) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Left ventricular diastolic dysfunction | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Fever in absence of neutropenia, ANC lt1.0x10e9/L | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Thrombosis/embolism (vascular access-related) | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Left ventricular systolic dysfunction | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Perforation, GI - Small bowel NOS | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Cognitive disturbance | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Leukocytes (total WBC) | 14 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Head/headache | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Edema: limb | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Lymphopenia | 10 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Thrombosis/thrombus/embolism | 19 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Diarrhea | 5 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Mood alteration - agitation | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Phosphate, serum-low (hypophosphatemia) | 5 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Thrombotic microangiopathy | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Mucositis/stomatitis (clinical exam) - Oral cavity | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Opportunistic inf associated w/gt=Gr 2 lymphopenia | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Colitis | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Muscle weakness, not d/t neuropathy - Extrem-lower | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Fracture | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Tinnitus | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Muscle weakness, not d/t neuropathy - body/general | 9 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Creatinine | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Thyroid function, low (hypothyroidism) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Musculoskeletal/Soft Tissue-Other (Specify) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Pain - Back | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Colitis, infectious (e.g., Clostridium difficile) | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Nausea | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Vision-blurred vision | 2 Participants |
| Lenalidomide and Dexamethasone | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Neuropathy: motor | 0 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Platelets | 7 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Confusion | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Neuropathy: sensory | 3 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Apnea | 1 Participants |
| Lenalidomide and Dexamethasone | Toxicity | Vomiting | 2 Participants |
| Dexamethasone | Toxicity | Apnea | 0 Participants |
| Dexamethasone | Toxicity | Ocular/Visual-Other (Specify) | 0 Participants |
| Dexamethasone | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Dexamethasone | Toxicity | Ophthalmoplegia/diplopia (double vision) | 1 Participants |
| Dexamethasone | Toxicity | Opportunistic inf associated w/gt=Gr 2 lymphopenia | 0 Participants |
| Dexamethasone | Toxicity | Constipation | 2 Participants |
| Dexamethasone | Toxicity | PTT (Partial thromboplastin time) | 1 Participants |
| Dexamethasone | Toxicity | Pain - Abdomen NOS | 2 Participants |
| Dexamethasone | Toxicity | Pain - Back | 2 Participants |
| Dexamethasone | Toxicity | Creatinine | 0 Participants |
| Dexamethasone | Toxicity | Pain - Bladder | 0 Participants |
| Dexamethasone | Toxicity | Pain - Bone | 3 Participants |
| Dexamethasone | Toxicity | Pain - Extremity-limb | 0 Participants |
| Dexamethasone | Toxicity | Cystitis | 1 Participants |
| Dexamethasone | Toxicity | Rash: acne/acneiform | 1 Participants |
| Dexamethasone | Toxicity | Pain - Head/headache | 1 Participants |
| Dexamethasone | Toxicity | AST, SGOT | 0 Participants |
| Dexamethasone | Toxicity | Pain - Joint | 1 Participants |
| Dexamethasone | Toxicity | Pain - Muscle | 1 Participants |
| Dexamethasone | Toxicity | Dehydration | 0 Participants |
| Dexamethasone | Toxicity | Pain - Pain NOS | 0 Participants |
| Dexamethasone | Toxicity | Pain - Stomach | 1 Participants |
| Dexamethasone | Toxicity | Pain-Other (Specify) | 1 Participants |
| Dexamethasone | Toxicity | Edema: limb | 1 Participants |
| Dexamethasone | Toxicity | Vomiting | 1 Participants |
| Dexamethasone | Toxicity | Pancreatic endocrine: glucose intolerance | 1 Participants |
| Dexamethasone | Toxicity | Dermatology/Skin-Other (Specify) | 1 Participants |
| Dexamethasone | Toxicity | Perforation, GI - Colon | 0 Participants |
| Dexamethasone | Toxicity | Perforation, GI - Small bowel NOS | 1 Participants |
| Dexamethasone | Toxicity | Phosphate, serum-low (hypophosphatemia) | 4 Participants |
| Dexamethasone | Toxicity | Diarrhea | 1 Participants |
| Dexamethasone | Toxicity | Albumin, serum-low (hypoalbuminemia) | 0 Participants |
| Dexamethasone | Toxicity | Platelets | 4 Participants |
| Dexamethasone | Toxicity | Pneumonitis/pulmonary infiltrates | 2 Participants |
| Dexamethasone | Toxicity | Dizziness | 1 Participants |
| Dexamethasone | Toxicity | Potassium, serum-low (hypokalemia) | 2 Participants |
| Dexamethasone | Toxicity | Prolonged QTc interval | 0 Participants |
| Dexamethasone | Toxicity | Proteinuria | 0 Participants |
| Dexamethasone | Toxicity | Dyspnea (shortness of breath) | 2 Participants |
| Dexamethasone | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 0 Participants |
| Dexamethasone | Toxicity | Rash/desquamation | 1 Participants |
| Dexamethasone | Toxicity | Encephalopathy | 0 Participants |
| Dexamethasone | Toxicity | Rash: erythema multiforme | 0 Participants |
| Dexamethasone | Toxicity | Renal failure | 1 Participants |
| Dexamethasone | Toxicity | Weight loss | 0 Participants |
| Dexamethasone | Toxicity | Fatigue (asthenia, lethargy, malaise) | 12 Participants |
| Dexamethasone | Toxicity | SVT and nodal arrhythmia - Atrial fibrillation | 2 Participants |
| Dexamethasone | Toxicity | Anorexia | 1 Participants |
| Dexamethasone | Toxicity | Sodium, serum-high (hypernatremia) | 1 Participants |
| Dexamethasone | Toxicity | Sodium, serum-low (hyponatremia) | 2 Participants |
| Dexamethasone | Toxicity | Febrile neutropenia | 0 Participants |
| Dexamethasone | Toxicity | Somnolence/depressed level of consciousness | 0 Participants |
| Dexamethasone | Toxicity | Colitis, infectious (e.g., Clostridium difficile) | 0 Participants |
| Dexamethasone | Toxicity | Syncope (fainting) | 0 Participants |
| Dexamethasone | Toxicity | Thrombosis/embolism (vascular access-related) | 0 Participants |
| Dexamethasone | Toxicity | Fever in absence of neutropenia, ANC lt1.0x10e9/L | 1 Participants |
| Dexamethasone | Toxicity | Thrombosis/thrombus/embolism | 5 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 1 Participants |
| Dexamethasone | Toxicity | Thyroid function, low (hypothyroidism) | 0 Participants |
| Dexamethasone | Toxicity | Tinnitus | 0 Participants |
| Dexamethasone | Toxicity | Fracture | 1 Participants |
| Dexamethasone | Toxicity | Vision-blurred vision | 3 Participants |
| Dexamethasone | Toxicity | Gastrointestinal-Other (Specify) | 0 Participants |
| Dexamethasone | Toxicity | Mood alteration - agitation | 1 Participants |
| Dexamethasone | Toxicity | Glomerular filtration rate | 0 Participants |
| Dexamethasone | Toxicity | Glucose, serum-high (hyperglycemia) | 18 Participants |
| Dexamethasone | Toxicity | Arthritis (non-septic) | 0 Participants |
| Dexamethasone | Toxicity | Glucose, serum-low (hypoglycemia) | 0 Participants |
| Dexamethasone | Toxicity | Heartburn/dyspepsia | 1 Participants |
| Dexamethasone | Toxicity | Hemoglobin | 5 Participants |
| Dexamethasone | Toxicity | Aspiration | 0 Participants |
| Dexamethasone | Toxicity | Hemorrhage, CNS | 0 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 2 Participants |
| Dexamethasone | Toxicity | Hemorrhage, GI - Colon | 0 Participants |
| Dexamethasone | Toxicity | Hypertension | 3 Participants |
| Dexamethasone | Toxicity | Ataxia (incoordination) | 1 Participants |
| Dexamethasone | Toxicity | Hypotension | 0 Participants |
| Dexamethasone | Toxicity | Hypoxia | 1 Participants |
| Dexamethasone | Toxicity | INR (of prothrombin time) | 2 Participants |
| Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 0 Participants |
| Dexamethasone | Toxicity | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus | 0 Participants |
| Dexamethasone | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 6 Participants |
| Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | 0 Participants |
| Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Up aerodigest | 0 Participants |
| Dexamethasone | Toxicity | CNS cerebrovascular ischemia | 2 Participants |
| Dexamethasone | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway | 2 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bladder | 0 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus | 1 Participants |
| Dexamethasone | Toxicity | Calcium, serum-high (hypercalcemia) | 1 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Colon | 1 Participants |
| Dexamethasone | Toxicity | Speech impairment (e.g., dysphasia or aphasia) | 0 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 3 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Up airway | 1 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Wound | 0 Participants |
| Dexamethasone | Toxicity | Calcium, serum-low (hypocalcemia) | 2 Participants |
| Dexamethasone | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-cran | 0 Participants |
| Dexamethasone | Toxicity | Mood alteration - anxiety | 1 Participants |
| Dexamethasone | Toxicity | Infection with unknown ANC - Lung (pneumonia) | 0 Participants |
| Dexamethasone | Toxicity | Infection with unknown ANC - Upper airway NOS | 1 Participants |
| Dexamethasone | Toxicity | Cardiopulmonary arrest, cause unknown (non-fatal) | 0 Participants |
| Dexamethasone | Toxicity | Infection-Other (Specify) | 1 Participants |
| Dexamethasone | Toxicity | Insomnia | 6 Participants |
| Dexamethasone | Toxicity | Joint-function | 0 Participants |
| Dexamethasone | Toxicity | Cataract | 1 Participants |
| Dexamethasone | Toxicity | Left ventricular diastolic dysfunction | 0 Participants |
| Dexamethasone | Toxicity | Thrombotic microangiopathy | 0 Participants |
| Dexamethasone | Toxicity | Left ventricular systolic dysfunction | 0 Participants |
| Dexamethasone | Toxicity | Leukocytes (total WBC) | 5 Participants |
| Dexamethasone | Toxicity | Lymphopenia | 5 Participants |
| Dexamethasone | Toxicity | Cognitive disturbance | 1 Participants |
| Dexamethasone | Toxicity | Mood alteration - depression | 8 Participants |
| Dexamethasone | Toxicity | Gastritis (including bile reflux gastritis) | 0 Participants |
| Dexamethasone | Toxicity | Mucositis/stomatitis (clinical exam) - Oral cavity | 1 Participants |
| Dexamethasone | Toxicity | Muscle weakness, not d/t neuropathy - Extrem-lower | 3 Participants |
| Dexamethasone | Toxicity | Colitis | 0 Participants |
| Dexamethasone | Toxicity | Muscle weakness, not d/t neuropathy - body/general | 4 Participants |
| Dexamethasone | Toxicity | Musculoskeletal/Soft Tissue-Other (Specify) | 2 Participants |
| Dexamethasone | Toxicity | Nausea | 1 Participants |
| Dexamethasone | Toxicity | Neuropathy: motor | 1 Participants |
| Dexamethasone | Toxicity | Neuropathy: sensory | 4 Participants |
| Dexamethasone | Toxicity | Confusion | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Proteinuria | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Weight loss | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Mood alteration - agitation | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Mood alteration - anxiety | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Neutrophils/granulocytes (ANC/AGC) | 7 Participants |
| Crossover to Rev+Dex | Toxicity | Speech impairment (e.g., dysphasia or aphasia) | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Thrombotic microangiopathy | 0 Participants |
| Crossover to Rev+Dex | Toxicity | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | AST, SGOT | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Albumin, serum-low (hypoalbuminemia) | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Anorexia | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Apnea | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Arthritis (non-septic) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Aspiration | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Dyspnea (shortness of breath) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Ataxia (incoordination) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Bilirubin (hyperbilirubinemia) | 1 Participants |
| Crossover to Rev+Dex | Toxicity | CNS cerebrovascular ischemia | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Calcium, serum-high (hypercalcemia) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Calcium, serum-low (hypocalcemia) | 3 Participants |
| Crossover to Rev+Dex | Toxicity | Cardiopulmonary arrest, cause unknown (non-fatal) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Cataract | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Cognitive disturbance | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Colitis | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Colitis, infectious (e.g., Clostridium difficile) | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Confusion | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Constipation | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Creatinine | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Cystitis | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Dehydration | 3 Participants |
| Crossover to Rev+Dex | Toxicity | Dermatology/Skin-Other (Specify) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Diarrhea | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Dizziness | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Encephalopathy | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Fatigue (asthenia, lethargy, malaise) | 8 Participants |
| Crossover to Rev+Dex | Toxicity | Febrile neutropenia | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Fever in absence of neutropenia, ANC lt1.0x10e9/L | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Fracture | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Gastritis (including bile reflux gastritis) | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Gastrointestinal-Other (Specify) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Glomerular filtration rate | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Glucose, serum-high (hyperglycemia) | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Glucose, serum-low (hypoglycemia) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Heartburn/dyspepsia | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Hemoglobin | 6 Participants |
| Crossover to Rev+Dex | Toxicity | Hemorrhage, CNS | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Hemorrhage, GI - Colon | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Hypertension | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Hypotension | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Hypoxia | 1 Participants |
| Crossover to Rev+Dex | Toxicity | INR (of prothrombin time) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Up aerodigest | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bladder | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Colon | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Up airway | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils - Wound | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-cran | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Infection with unknown ANC - Lung (pneumonia) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Infection with unknown ANC - Upper airway NOS | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Infection-Other (Specify) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Insomnia | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Joint-function | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Left ventricular diastolic dysfunction | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Left ventricular systolic dysfunction | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Leukocytes (total WBC) | 4 Participants |
| Crossover to Rev+Dex | Toxicity | Lymphopenia | 8 Participants |
| Crossover to Rev+Dex | Toxicity | Mood alteration - depression | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Mucositis/stomatitis (clinical exam) - Oral cavity | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Muscle weakness, not d/t neuropathy - Extrem-lower | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Muscle weakness, not d/t neuropathy - body/general | 3 Participants |
| Crossover to Rev+Dex | Toxicity | Musculoskeletal/Soft Tissue-Other (Specify) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Nausea | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Neuropathy: motor | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Neuropathy: sensory | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Ocular/Visual-Other (Specify) | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Ophthalmoplegia/diplopia (double vision) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Opportunistic inf associated w/gt=Gr 2 lymphopenia | 1 Participants |
| Crossover to Rev+Dex | Toxicity | PTT (Partial thromboplastin time) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Abdomen NOS | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Back | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Bladder | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Bone | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Extremity-limb | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Head/headache | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Joint | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Muscle | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Pain NOS | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain - Stomach | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Pain-Other (Specify) | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Pancreatic endocrine: glucose intolerance | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Perforation, GI - Colon | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Perforation, GI - Small bowel NOS | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Vomiting | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Phosphate, serum-low (hypophosphatemia) | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Platelets | 3 Participants |
| Crossover to Rev+Dex | Toxicity | Pneumonitis/pulmonary infiltrates | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Potassium, serum-low (hypokalemia) | 3 Participants |
| Crossover to Rev+Dex | Toxicity | Prolonged QTc interval | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Edema: limb | 2 Participants |
| Crossover to Rev+Dex | Toxicity | Pulmonary/Upper Respiratory-Other (Specify) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Rash/desquamation | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Rash: acne/acneiform | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Rash: erythema multiforme | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Renal failure | 2 Participants |
| Crossover to Rev+Dex | Toxicity | SVT and nodal arrhythmia - Atrial fibrillation | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Sodium, serum-high (hypernatremia) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Sodium, serum-low (hyponatremia) | 3 Participants |
| Crossover to Rev+Dex | Toxicity | Somnolence/depressed level of consciousness | 1 Participants |
| Crossover to Rev+Dex | Toxicity | Syncope (fainting) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Thrombosis/embolism (vascular access-related) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Thrombosis/thrombus/embolism | 5 Participants |
| Crossover to Rev+Dex | Toxicity | Thyroid function, low (hypothyroidism) | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Tinnitus | 0 Participants |
| Crossover to Rev+Dex | Toxicity | Vision-blurred vision | 1 Participants |