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This study is designed to test the safety and efficacy of lenalidomide in older patients (age > 60 years) with untreated acute myeloid leukemia without chromosomal abnormalities involving 5q.
The incidence of AML increases with age, and current treatment options for the older patient population with newly diagnosed AML (AML >= 60) is limited, all with poor outcomes. AML >= 60 patients are more likely to have poor-risk cytogenetics abnormalities, and many have a preceding myelodysplastic syndrome (MDS). Traditional induction chemotherapy approaches in AML with cytarabine and anthracyclines yield remissions in 45-60% of AML >= 60, however the vast majority of these patients relapse with a median survival of about 9 months. These patients are rarely candidates for potentially curative allogeneic stem cell transplantation. Many untreated AML >= 60 patients are not candidates for aggressive therapy, and those who do receive therapy have a significant induction mortality of 10-20%, and significant hematologic toxicity occurs in over 30%, with no change in overall survival compared with supportive care. AML >= 60 patients with favorable risk cytogenetics have a modest improvement in prognosis, for example with a 5 year overall survival of ~20%, compared with 0% in other cytogenetic categories. Thus, all eligible patients with AML >= 60 should be recommended a clinical trial, regardless of whether they would be offered generally ineffective traditional induction chemotherapy. More effective and less toxic therapies are needed for the treatment of AML in this older patient population, indeed the preferred first line therapy in the national cancer center network (NCCN) guidelines for AML is a clinical trial.
In trials of lenalidomide in patients with MDS the dose of lenalidomide has been reduced for myelotoxicity and/or thrombocytopenia. However, current paradigms for the therapy of acute myeloid leukemia are based on using high doses of myelosuppressive chemotherapy and supporting the patient through a 4-5 weeks period of neutropenia/thrombocytopenia in an attempt to eliminate the malignant clone. Based on its efficacy in the related myeloid disorder MDS, and the close relationship between MDS and AML in patients > 60, this trial employs the same paradigm of myelosuppressive therapy using high dose lenalidomide instead of chemotherapy. Importantly, within the MDS trials using low doses of lenalidomide, responses were observed in 3/9 (33%) of patients with excess blasts (RAEB/RAEB-t), which are now classified as evolving into AML or AML. This suggests that the therapeutic effect of lenalidomide occurs in the setting of a large percentage of blasts, such as AML, although the dose and schedule of lenalidomide administration is different. The response of AML >= 60 patients to the proposed high dose lenalidomide regimen is unknown. Following high dose lenalidomide, in those patients that have a response, we propose using a lower dose maintenance strategy similar to the FDA approved dosing for MDS. The maintenance phase will include standard dose reductions for unacceptable toxicities.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles. |
|
| Cohort 2 | Experimental | Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lenalidomide | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Complete Remission Rate (CRm + CRi + CRc) | CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability (Removal From Study Due to Adverse Events) | Toxicity will be scored using CTCAE Version 3.0 for toxicity and adverse event reporting | 4 weeks after last dose of study drug [median duration of therapy was 65 days (range, 3-413 days)] |
| Response Rate (RR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ravi Vij, M.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15703420 | Background | List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10;352(6):549-57. doi: 10.1056/NEJMoa041668. | |
| Background | List, AF, G Dewald, J Bennett, et al. 2005. Hematologic and Cytogenetic (CTG) Response to Lenalidomide (CC-5013) in Patients with Transfusion-Dependent (TD) Myelodysplastic Syndrome (MDS) and Chromosome 5q31.1 Deletion: Results of the Multicenter MDS-003 Study. In ASCO, Orlando, FL. | ||
| 29567774 |
| Label | URL |
|---|---|
| Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine | View source |
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The study opened to participant enrollment on 02/02/2007 and closed to participant enrollment on 03/04/2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles. |
| FG001 | Cohort 2 | Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles. |
| BG001 | Cohort 2 |
| 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 | Complete Remission Rate (CRm + CRi + CRc) | CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). | 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2. | Number | participants | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
|
Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
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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 | Cohort 1 | Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ravi Vij, M.D. | Washington University School of Medicine | 314-454-8304 | rvij@dom.wustl.edu |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077269 | Lenalidomide |
| ID | Term |
|---|---|
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
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RR = as patients obtaining any response (CRm + CRc +CRi + PR). CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. CRc = Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. Partial remission (PR): Requires |
| After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
| Morphologic Leukemia Free State | Morphologic leukemia-free state: Defined as < 5% blasts on the BM aspirate with spicules and a count of > 200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease. | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
| Morphologic Complete Remission Rate (CRm) | CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
| Cytogenetics CR Rate (CRc) | Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
| CR With Complete Blood Counts (CRi) Rate | CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
| Partial Remission Rate (PR) | Partial remission (PR): Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission. | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
| Overall Survival (OS) | Overall survival: Defined as the date of first dose of study drug to the date of death from any cause. | 2 years |
| Event Free Survival (EFS) | Event free survival: Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause. | 2 years |
| Progression-free Survival | Progression-free survival (PFS) denotes the chances of staying free of disease progression for a group of individuals suffering from a cancer after a particular treatment. It is the percentage of individuals in the group whose disease is likely to remain stable (and not show signs of progression) after a specified duration of time. Progression-free survival rates are an indication of how effective a particular treatment is. | 2 years |
| Relapse Free Survival (RFS) for Complete Responders | This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause. | 2 years |
| Duration of CR for Complete Responders | Duration of remission: Defined as the interval from the date complete remission is documented to the date of recurrence | 2 years |
| Changes in NK Cell Number and Function | Peripheral blood mononuclear cells (PBMC) will be viably cryopreserved from patients at baseline (pre-therapy, newly diagnosed AML), during lenalidomide therapy, and posttherapy. Following sample collection, PBMC will be thawed, and flow cytometry will be performed to assess NK cell number (CD56+CD3-), subsets, and phenotype utilizing the Siteman Cancer Center Flow Cytometry / Cell Sorting Core. In addition, NK cell function will be assessed in flow based killing assays using PBMC (containing NK cells) as effectors and NK sensitive cell lines (K562) and/or autologous leukemic blasts as target cells. Thus, analyzing these parameters in patients before, during, and after therapy will provide a comprehensive evaluation of the ability of lenalidomide to modulate NK cells in patients in vivo. | Baseline, during therapy, and posttherapy |
| Gene Expression Profiles of Bone Marrow and Peripheral Blood | RNA will be made from total bone marrow cells for labeling and evaluations by RNA profiling. Cellular RNA and corresponding biotinylated cRNA targets will be prepared and hybridized with Affymetrix GeneChip® microarrays within the Multiplexed Gene Analysis SCC Core (Dr. Mark Watson, Director). Microarray data (and eventually corresponding gene sequence data) will be integrated an analyzed with state-of-the-art software packages. The pre- and post-treatment RNA profiling studies will be used as a discovery tool. Patterns of gene expression before and after lenalidomide therapy will be compared within each patient's sample to identify genes with altered expression after lenalidomide therapy. In addition, supervised algorithms will be sued to identify genes that can potentially predict clinical outcome and response to lenalidomide therapy. | Pre and post treatment |
| Plasma Proteins Via Proteomics | Proteomic analysis will be performed within the Siteman Cancer Center proteomics core on pre- and post-treatment plasma samples. This pilot proteomic study will identify candidate proteins of interest with altered expression after treatment with lenalidomide. This approach will provide an unbiased method to assess global changes in serum proteins following lenalidomide therapy. | Pre and post treatment |
| Derived |
| Bansal D, Vij K, Chang GS, Miller CA, DiPersio JF, Vij R, Heath SE, Westervelt P, Welch JS, Fehniger TA. Lenalidomide results in a durable complete remission in acute myeloid leukemia accompanied by persistence of somatic mutations and a T-cell infiltrate in the bone marrow. Haematologica. 2018 Jun;103(6):e270-e273. doi: 10.3324/haematol.2017.184168. Epub 2018 Mar 22. No abstract available. |
| 21051557 | Derived | Fehniger TA, Uy GL, Trinkaus K, Nelson AD, Demland J, Abboud CN, Cashen AF, Stockerl-Goldstein KE, Westervelt P, DiPersio JF, Vij R. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood. 2011 Feb 10;117(6):1828-33. doi: 10.1182/blood-2010-07-297143. Epub 2010 Nov 4. |
| 18824593 | Derived | Fehniger TA, Byrd JC, Marcucci G, Abboud CN, Kefauver C, Payton JE, Vij R, Blum W. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood. 2009 Jan 29;113(5):1002-5. doi: 10.1182/blood-2008-04-152678. Epub 2008 Sep 29. |
Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status |
| Number | participants |
|
| Cytogenetic Risk Category | Number | participants |
|
| Description |
|---|
| OG000 | Cohort 1 | Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles. |
| OG001 | Cohort 2 | Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy. |
|
|
| Secondary | Safety and Tolerability (Removal From Study Due to Adverse Events) | Toxicity will be scored using CTCAE Version 3.0 for toxicity and adverse event reporting | Number | participants | 4 weeks after last dose of study drug [median duration of therapy was 65 days (range, 3-413 days)] |
|
|
|
| Secondary | Response Rate (RR) | RR = as patients obtaining any response (CRm + CRc +CRi + PR). CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. CRc = Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. Partial remission (PR): Requires | 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2. | Number | participants | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
|
|
|
| Secondary | Morphologic Leukemia Free State | Morphologic leukemia-free state: Defined as < 5% blasts on the BM aspirate with spicules and a count of > 200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease. | 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2. | Number | participants | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
|
|
|
| Secondary | Morphologic Complete Remission Rate (CRm) | CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. | 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2. | Number | participants | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
|
|
|
| Secondary | Cytogenetics CR Rate (CRc) | Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). | 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2. | Number | participants | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
|
|
|
| Secondary | CR With Complete Blood Counts (CRi) Rate | CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. | 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2. | Number | participants | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
|
|
|
| Secondary | Partial Remission Rate (PR) | Partial remission (PR): Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission. | 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2. | Number | participants | After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2) |
|
|
|
| Secondary | Overall Survival (OS) | Overall survival: Defined as the date of first dose of study drug to the date of death from any cause. | Participants in Cohort 1 were not analyzed for overall survival because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease. | Median | 95% Confidence Interval | months | 2 years |
|
|
|
| Secondary | Event Free Survival (EFS) | Event free survival: Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause. | Event free survival was not analyzed. Progression free survival was analyzed instead. | 2 years |
|
|
| Secondary | Progression-free Survival | Progression-free survival (PFS) denotes the chances of staying free of disease progression for a group of individuals suffering from a cancer after a particular treatment. It is the percentage of individuals in the group whose disease is likely to remain stable (and not show signs of progression) after a specified duration of time. Progression-free survival rates are an indication of how effective a particular treatment is. | Participants in Cohort 1 were not analyzed for progression-free survival because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease. | Median | 95% Confidence Interval | months | 2 years |
|
|
|
| Secondary | Relapse Free Survival (RFS) for Complete Responders | This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause. | Participants in Cohort 1 were not analyzed for relapse free survival because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease. | Median | 95% Confidence Interval | months | 2 years |
|
|
|
| Secondary | Duration of CR for Complete Responders | Duration of remission: Defined as the interval from the date complete remission is documented to the date of recurrence | Participants in Cohort 1 were not analyzed for duration of remission because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease. | Median | Full Range | months | 2 years |
|
|
|
| Secondary | Changes in NK Cell Number and Function | Peripheral blood mononuclear cells (PBMC) will be viably cryopreserved from patients at baseline (pre-therapy, newly diagnosed AML), during lenalidomide therapy, and posttherapy. Following sample collection, PBMC will be thawed, and flow cytometry will be performed to assess NK cell number (CD56+CD3-), subsets, and phenotype utilizing the Siteman Cancer Center Flow Cytometry / Cell Sorting Core. In addition, NK cell function will be assessed in flow based killing assays using PBMC (containing NK cells) as effectors and NK sensitive cell lines (K562) and/or autologous leukemic blasts as target cells. Thus, analyzing these parameters in patients before, during, and after therapy will provide a comprehensive evaluation of the ability of lenalidomide to modulate NK cells in patients in vivo. | This outcome was not analyzed for either Cohort due to number of samples collected. | Baseline, during therapy, and posttherapy |
|
|
| Secondary | Gene Expression Profiles of Bone Marrow and Peripheral Blood | RNA will be made from total bone marrow cells for labeling and evaluations by RNA profiling. Cellular RNA and corresponding biotinylated cRNA targets will be prepared and hybridized with Affymetrix GeneChip® microarrays within the Multiplexed Gene Analysis SCC Core (Dr. Mark Watson, Director). Microarray data (and eventually corresponding gene sequence data) will be integrated an analyzed with state-of-the-art software packages. The pre- and post-treatment RNA profiling studies will be used as a discovery tool. Patterns of gene expression before and after lenalidomide therapy will be compared within each patient's sample to identify genes with altered expression after lenalidomide therapy. In addition, supervised algorithms will be sued to identify genes that can potentially predict clinical outcome and response to lenalidomide therapy. | This outcome measure was not analyzed for either Cohort due to sample collection. | Pre and post treatment |
|
|
| Secondary | Plasma Proteins Via Proteomics | Proteomic analysis will be performed within the Siteman Cancer Center proteomics core on pre- and post-treatment plasma samples. This pilot proteomic study will identify candidate proteins of interest with altered expression after treatment with lenalidomide. This approach will provide an unbiased method to assess global changes in serum proteins following lenalidomide therapy. | This outcome was not analyzed for either Cohort due to sample collection. | Pre and post treatment |
|
|
| 10 |
| 15 |
| 15 |
| 15 |
| EG001 | Cohort 2 | Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy. | 25 | 33 | 33 | 33 |
| Pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gouty arthritis | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Death due to progressive disease | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Staph hominis bacteremia infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Catheter line infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Opportunistic fungal infection - death | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Lower extremity weakness | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Syncope | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Petichae | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Death due to CNS hemorrhage | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gram-cocci infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypernatremia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypokalemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophils | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Splenic infarction | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Streptococcus bacteremia infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Death due to acute renal failure | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chest pain | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Subdural hematoma | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| E. Coli infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Coryn bacterium miutissimum sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Staphylcoccus epidermidis sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mental status | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gram positive sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Liver dysfunction | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tonsil fistula | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Coagulase negative staphylococcus sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Cardiac ischemia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| C. difficile colitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Upper GI hemorrhage | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lower GI hemorrhage | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Left ventricular diastolic dysfunction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Actinic keratosis | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alkaline phosphatase | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Alkylosis | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Allergic reaction/hypersensitivity | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Back spasms | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bilirubin | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Biopsy site pain | Surgical and medical procedures | CTCAE (3.0) | Systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| CNS hemorrhage | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cardiac ischemia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cardiopulmonary arrest | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chest pain | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chest wall pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Creatinine | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Cystitis | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Decubitus | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dental abscess | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dental pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diverticulosis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Esophagitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Eye hemorrhage | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Feet pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever (no infection) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Floaters | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Generalized pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hand pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hard palate ulcer | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hematoma | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhagic lesion | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhoid pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperglycemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hyperkalemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypermagnesemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypernatremia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperuricemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypoalbuminemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypocalcemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypokalemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hyponatremia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypophosphatemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| INR | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Incontinence - anal | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - cellulitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - clostridium difficile | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - enterococcus faecium | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - escheria coli | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - oral candidiasis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - parainfluenza | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - polymicrobial sepsis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - stapphylococcus | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - unspecified | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - upper respiratory | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - urinary tract | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/neutropenia - vaginal | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/o neutropenia - bronchitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/o neutropenia - catheter fungemia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/o neutropenia - coagulase negative staphylococcus bacteremia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/o neutropenia - middle ear | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/o neutropenia - oral candidiasis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/o neutropenia - pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection w/o neutropenia - upper respiratory | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Inguinal hernia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Knee pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Left ventricular systolic dysfunction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Leukocytes (WBC) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Liver dysfunction | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lower GI NOS hemorrhage | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lower back pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lymphocele | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lymphopenia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration - agitation | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration - anxiety | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration - depression | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness - generalized | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness - lower extremity | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neck nodule | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophils (ANC) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Nose bleed | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Peridontal - mandible swelling | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Periodontal - poor dentition | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Petechiae | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Progressive disease | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pruritis | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Psychosis - hallucinations | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rectal hemorrhage | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rib pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| SGOT (AST) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| SGPT (ALT) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Sensory neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Shoulder pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinus drainage | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Skin sore | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Spinal stenosis | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Splenic infarction | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Supraventricular arrhythmia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sweating | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Syncope | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Taste alteration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Throat pain | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombosis | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tingling in extremities | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tonsil fistula | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tremors | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Upper extremity pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vasculitis | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ventricular tachycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (3.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009930 |
| Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| CRi |
|
| PR |
|