scholarly journals Postoperative opioid sparing with injectable hydroxypropyl-β-cyclodextrin-diclofenac: pooled analysis of data from two Phase III clinical trials

2016 ◽  
Vol Volume 10 ◽  
pp. 15-29 ◽  
Author(s):  
Tong Gan ◽  
Neil Singla ◽  
Stephen E Daniels ◽  
Douglas Hamilton ◽  
Peter Lacouture ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Clinical Trials ◽  
Beta Cyclodextrin ◽  
Opioid Sparing ◽  
Hydroxypropyl Beta Cyclodextrin

scholarly journals Efficacy of Daratumumab Based Regimens Compared to Standard of Care for Transplant Eligible Multiple Myeloma in Phase III Clinical Trials: A Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-36
Author(s):  
Zahoor Ahmed ◽  
Karun Neupane ◽  
Rabia Ashraf ◽  
Amna Khan ◽  
Abdul Rafae ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Standard Care ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Control Group ◽  
Newly Diagnosed ◽  
Two Phase ◽  
Randomized Controlled ◽  
Phase Iii Clinical Trials

Introduction: Daratumumab (Dara) is a human anti-CD38 monoclonal antibody approved for multiple myeloma (MM) treatment. Dara has shown promising efficacy and a favorable safety profile in newly diagnosed (ND) and relapsed refractory MM patients. This study is focused on the efficacy and safety of Dara when added to the standard care regimen in transplant eligible newly diagnosed MM (NDMM) in phase III clinical trials. Methods: We performed a comprehensive literature search on four databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov). Our search strategy included MeSH (Medical Subject Headings) terms and keywords for multiple myeloma and Dara including trade names and generic names from date of inception to May 2020. Initial search revealed 588 articles. After a detailed screening, two phase III randomized clinical trials were included, which reported overall response rate (ORR) and negative minimal residual disease (MRD) in transplant eligible MM patients with Dara addition to standard care regimen. Odds ratios (OR) of ORR and MRD were computed along with 95% confidence intervals (CI) for pooled analysis using a fixed-effect model in RevMan v.5.4. Results: A total of 1292 transplant eligible NDMM patients were enrolled and evaluated in two phase III randomized controlled trials. Six hundred and forty-seven patients were in the Dara group and 645 patients were in the control group. Moreau et al. (2019) studied the efficacy of Dara + bortezomib (V) + thalidomide (T) + dexamethasone (d) vs VTd in NDMM pts (n=1085) in CASSIOPEIA phase III trial. Vorhees et al. reported efficacy of Dara addition to lenalidomide (R), and Vd vs RVd in GRIFFIN study in transplant eligible NDMM patients (n= 207). Dara dose was 16 mg/kg in both studies and the median follow-up was 18.8 months and 22.1 months in CASSIOPEIA and GRIFFIN trial, respectively. A pooled analysis of these trials showed ORR (OR: 1.73, 95% CI 1.16-2.59; p < 0.008, I2 = 80%). Achievement of MRD negative status was significant in Dara based regimen as compared to control group (OR: 2.47, 95% CI 1.97-3.10; p < 0.00001, I2 = 66%). Dara addition to standard care regimen (Rd and VMP) also decreased the risk of progressive disease (OR: 0.74, 95% CI 0.43-1.28; p < 0.28, I2 = 0%). However, Dara based regimens increased the risk of neutropenia (OR: 3.41, 95% CI 2.68-4.33; p < 0.00001, I2 = 91%), and lymphopenia (OR: 3.43, 95% CI 2.71-4.34; p < 0.0001, I2 = 94%), and pyrexia (OR: 1.42 95% CI 1.11-1.82: p < 0.005, I2=50%) (Figure 1). Conclusion: Addition of Dara to the standard care regimen (VRd, VTd) for transplant eligible NDMM achieved the surrogate endpoints with improved efficacy and MRD negative status with manageable toxicity. However, data from more randomized controlled trials are needed. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Impact of elagolix on work loss due to endometriosis-associated pain: estimates based on the results of two phase III clinical trials

2019 ◽  
Vol 112 (3) ◽  
pp. 545-551 ◽  
Author(s):  
Robin M. Pokrzywinski ◽  
Ahmed M. Soliman ◽  
Jun Chen ◽  
Michael Snabes ◽  
Michael P. Diamond ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Iii ◽  
Work Loss ◽  
Two Phase ◽  
Phase Iii Clinical Trials

Efficacy of Daratumumab Based Regimens Compared to Standard of Care for Transplant Ineligible Newly Diagnosed Multiple Myeloma in Phase III Clinical Trials: A Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-33
Author(s):  
Zahoor Ahmed ◽  
Karun Neupane ◽  
Rabia Ashraf ◽  
Amna Khan ◽  
Moazzam Shahzad ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Standard Care ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Control Group ◽  
Two Phase ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Phase Iii Clinical Trials

Introduction: Daratumumab (Dara) is a human anti-CD38 monoclonal antibody approved for multiple myeloma (MM) treatment. Dara has a promising efficacy and a favorable safety profile in newly diagnosed MM (NDMM) patients. This study is focused on the efficacy and safety of Dara when added to the standard care regimen in transplant ineligible NDMM in phase III clinical trials. Methods: We performed a comprehensive database search on four major databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov). Our search strategy included MeSH (Medical Subject Headings) terms and key words for multiple myeloma and Dara including trade names and generic names from date of inception to May 2020. Initial search revealed 587 articles. After excluding review articles, duplicates, and non-relevant articles, two phase III clinical trials were included which reported overall response rate (ORR), and progression free survival (PFS) of transplant ineligible NDMM patients with Dara addition to standard care regimen. Odds ratios (OR) of ORR were computed and hazard ratios (HR) of PFS (along with 95% confidence intervals; CI) were extracted to compute a pooled HR using a fixed effect model in RevMan v.5.4. Results: A total of 1453 transplant ineligible NDMM patients were enrolled and evaluated in two phase III randomized clinical trials. Seven hundred and eighteen patients were in Dara group and 735 patients were in control group. Bahlis et al. (2019) studied Dara + lenolidamide (R) and dexamethasone (d) vs Rd in NDMM pts (n=737) in MAIA phase III trial. Similarly, Mateos et al. (2018) reported the role of Dara + bortezomib (V) + melphalan (M), and prednisone (P) vs VMP in NDMM pts (n=706) in a phase III trial (Alcyone). A pooled analysis of these phase III trials showed ORR (OR: 3.26, 95% CI 2.36-4.49; p < 0.00001, I2 = 0%), and progression free survival (PFS) (HR: 0.53, 95% CI 0.43-0.65; p < 0.00001, I2 = 0%). Achievement of minimal residual disease (MRD) negative status was significant in Dara based regimen as compared to control group (OR: 4.49, 95% CI 3.31-6.37; p < 0.00001, I2 = 0%). Dara addition to standard care regimen (Rd and VMP) decreased the risk of progression/death to 42% (HR: 0.58, 95% CI 0.48-0.70; p < 0.00001, I2 = 0%). The addition of Dara increased the risk of neutropenia (OR: 1.41, 95% CI 1.07-1.85; p < 0.02, I2 = 44%), and pneumonia (OR: 2.25, 95% CI 1.54-3.29; p < 0.0001, I2 = 37%) vs control group. However, decreased risk of anemia (OR: 0.64, 95% CI 0.49-0.85: p < 0.002, I2=30%) was observed in Dara group vs control group (Figure 1). Conclusion: Addition of Dara to the standard care regimen for transplant ineligible NDMM achieved the surrogate end points with improved efficacy and MRD negative status with manageable toxicity. However, data from more randomized controlled trials is needed. Table Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

SNP Associations with Event Free Survival in Myeloma from Two Phase III Clinical Trials Using the Bank On A Cure Chip.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 131-131
Author(s):  
Brian G. Van Ness ◽  
John C. Crowley ◽  
Christine Ramos ◽  
Suzanne M. Grindle ◽  
Antje Hoering ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Genetic Variations ◽  
Gene Set Enrichment Analysis ◽  
Phase Iii ◽  
Survival Outcomes ◽  
Cellular Functions ◽  
Two Phase ◽  
Data Set ◽  
Phase Iii Clinical Trials ◽  
Statistical Approaches

Abstract While there are certain common clinical features in myeloma, the disease shows significant heterogeneity with regard to disease progression, and responses to therapy, affecting both survival and toxicities. Heritable variations in a wide variety of genes and pathways affecting cellular functions and drug responses likely impact patient outcomes. In the Bank On A Cure (BOAC) program we have developed a custom chip that assesses 3,404 SNPs representing variations in cellular functions and pathways that may be involved in myeloma progression and response. The chip has gone through rigorous quality controls checks for high call rates, accuracy, and reproducibility that will be presented. Using the BOAC chip, we have conducted studies to look for SNPs that may identify biologic variations that are associated with good or poor response across a variety of treatments. In this study we looked for SNPs that may distinguish short term and long term survivors in two phase III clinical trials: ECOG E9486 and intergroup trial S9321. E9487 patients were treated with VBMCP followed by randomization to no further treatment, IFN-alpha, or cylcophosphamide; and, although there was variation in survival, no significant differences in survival were noted among the 3 arms of the trial. Patients included in this SNP study from S9321 received VAD induction followed by randomization to VBMCP or high dose melphalan + TBI. SNP profiles were obtained for patients with less than 1 year EFS (n=20 in E9487; n=50 in S9321) and patients showing greater than 3 years EFS (n=32 in E9486; n=41 in S9321). Statistical approaches were performed to identify single and groups of SNPs that best discriminated the survival groups. Previous studies have suggested genetic variations in drug metabolism genes, p-glycoprotein transport, and DNA repair genes may influence survival outcomes. Our results show significant survival associations of genetic variations in genes within these functional categories (eg. GST, XRCC, ABCB, and CYP genes). Although genetic variations were found that were uniquely associated with each clinical trial, several of these genetic variations show survival associations that increase in significance when the two trials were examined as a conglomerate data set. Grouping genetic variations through common pathway approaches using gene set enrichment analysis, as well as clustering or partitioning algorithms, further improve the value of the SNPs as potential prognostic markers of survival outcomes. These results and statistical approaches will be presented, and represent steps toward identifying patient variations in biologic mechanisms important in predicting therapeutic outcomes.

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