bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severity, implications, and understanding of cancer related fatigue in cancer survivors of South Asian ethnicity.
Authors: Nayyar Harleen Kaur , Hussain Shaik Maheboob , Thakur Ruchika , Sonthwal Neha , Chaturvedi Harit Kumar , Gupta Alok 
Published: March 2020

e23177 Background: Cancer Related Fatigue (CRF) is a common debilitating symptom among cancer survivors that interferes with their Quality of Life (QOL). We evaluated incidence, severity, perception and implications of CRF on QOL among cancer survivors of South Asian ethnicity. Methods: Between July & December 2018, cancer survivors who visited cancer follow up clinic were asked to participate in this study by filling CRF questionnaire which focused on evaluating an individual’s assessment of severity, perception of causes and implications of CRF on their QOL as well as the measures taken to overcome CRF. Results: 160 cancer survivors, median age 52 years, 125 female & 34 male with most common diagnosis of breast cancer(60%) participated in the study. All survivors had received ≥2 treatment modalities. Overall, 133(84%) underwent surgery, 144(91%) received chemotherapy, 103(65%) received radiation therapy, 60(38%) received hormonal therapy & 34(21%) received targeted therapy. 36(23%) experienced weight loss and 26(16%) required blood transfusion. 148(93%) survivors reported CRF of any grade. 82(52%) reported moderate intensity CRF(affecting work but not activities of daily living) while 33(21%) reported severe intensity CRF (affecting activities of daily living). CRF was perceived as generalized weakness by 137(86.2%), emotional labiality by 42(26%), diminished concentration/attention span by 36(23%) and decreased motivation/interest in usual activities by 29(18%) survivors. CRF was attributed to treatment of cancer by 137(86%), psychological and social factors by 50(31%), cancer itself by 34(21%) and environmental /genetic factors by 16(10%) survivors. CRF adversely affected various aspects of QOL including activities of daily living in 79(50%), mood in 74(47%), professional work in 46(29%) and interpersonal relationships in 36(23%) survivors. To overcome CRF, 70(44%) survivors increased physical activity, 61(38%) resorted to mind-body interventions, 29 (18%) took pharmacological intervention and 25 (16%) resorted to psychosocial interventions. CRF resolved within 3 months after completion of therapy in 29(18%), 3-6 months in 23(15%), 6-12 months in 23(15%) and > 12 months in 1 survivor. CRF persisted in 78(49%) survivors. Conclusions: Incidence & severity of CRF is high in cancer survivors of South Asian ethnicity. Persistence of CRF beyond treatment completion significantly affects QOL and remains a poorly understood & incompletely addressed health issue among cancer survivors. More research is warranted in this field.
Phase I/II clinical trial of NY-ESO-1-specific TCR-engineered T-cell transfer combined with a novel T-cell stimulator CHP:NE1 for patients with refractory soft tissue sarcoma.
Authors: Ishihara Mikiya , Hattori Hiroyoshi , Arai Eisuke , Nishida Yoshihiro , Takada Kohichi , Emori Makoto , Kawai Akira , Ueda Takafumi , Endo Makoto , Matsumoto Yoshihiro , Sasada Tetsuro , Sato Eiichi , Yamada Tomomi , Matsumine Akihiko , Nagata Yasuhiro , Harada Naozumi , Shiku Hiroshi , Kageyama Shinichi 
Published: March 2020

TPS11074 Background: Combination therapy to enhance the efficacy of T cell receptor (TCR)-engineered T cells (TCR-T) has received increasing attention. We found that a combination therapy of TCR-T and a long peptide vaccine with CpG adjuvant without lymphodepletion regimen caused regression of immune checkpoint inhibitor-resistant sarcoma in a preclinical mouse model. Based on this finding, we initiated a clinical trial of TBI-1301 combined with CHP:NE1 without lymphodepletion for the patients with NY-ESO-1-expressing advanced soft tissue sarcoma. TBI-1301 is an NY-ESO-1157–165/HLA-A*02:01- or -A*02:06-specific TCR-T engineered to reduce endogenous TCR mRNA expression. CHP:NE1 is a novel T cell stimulator consisting of NY-ESO-1 long peptide antigen, cholesteryl pullulan (CHP) nanogel, and CpG oligoDNA. CHP nanogel is used for efficient delivery of long peptide antigen into the lymph nodes. CpG oligoDNA is a TLR9 agonist and used as an adjuvant. CHP:NE1 is expected to reinforce TBI-1301 T cells in the lymph nodes. Methods: This is an investigator-initiated multi-institutional first-in-human phase I/II clinical trial. TBI-1301 is infused at 5×109 cells one day after subcutaneous injection of CHP:NE1. CHP:NE1 is injected again 7 days after TBI-1301 infusion. This cycle is repeated once more. Lymphodepletion using cyclophosphamide and/or fludarabine is not performed. Key inclusion criteria include: refractory soft tissue sarcoma with NY-ESO-1 antigen expression, HLA-A*02:01- or HLA-A*02:06- positive, ECOG Performance Status 0 or 1, and adequate organ function. The primary objective is to assess the safety and efficacy in the phase 1 and 2 parts, respectively. The secondary objective is to assess the efficacy and immune response (blood concentration, immunophenotype and activity of TBI-1301) in the phase 1 part and the safety and immune response in the phase 2 part. Enrollment in this study is currently ongoing. Clinical trial information: JMA-IIA00346.
A phase I trial of palbociclib in combination with dexamethasone in relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).
Authors: Kasner Margaret T. , Wilde Lindsay , Keiffer Gina , Palmisiano Neil David , Calabretta Bruno 
Published: March 2020

TPS7065 Background: c-Myb is a DNA-binding transcription factor that is highly expressed in immature hematopoietic cells. c-Myb and its products are essential in regulating normal hematopoiesis and influencing leukemogenesis. Knockdown of c-Myb causes cell cycle arrest and apoptosis in pre-B-ALL cells. The effects of c-Myb depend on transcriptional regulation of CDK6 and Bcl-2. c-Myb-silenced Ph+ ALL cells exhibit Rb-dependent cell cycle arrest and apoptosis, both of which are rescued by ectopic expression of cyclin D3, CDK6, and Bcl-2 expression. Preclinical studies suggest that the cytotoxic activity of dexamethasone in ALL cells may be due to decreased c-Myb expression and reduced Bcl-2 levels. Thus, the novel combination of palbociclib, a small molecule CDK4/6 inhibitor, and dexamethasone is a logical approach for the treatment of B-cell ALL. Methods: This is a single arm, phase I, dose escalation study with a traditional 3+3 design. Adult patients with relapsed or refractory B-cell ALL are eligible. Patients with Ph+ ALL must be refractory to or intolerant of standard tyrosine kinase inhibitor therapy. Patients receive a 1-week lead-in of palbociclib alone followed by induction with 4 weeks of palbociclib and dexamethasone. If an adequate response is seen, patients move to maintenance therapy, which consists of 1 week of palbociclib plus dexamethasone followed by 3 weeks of palbociclib alone. Treatment continues until disease progression, dose limiting toxicity, or availability of an alternative therapy. The primary endpoints are dose limiting toxicity and maximum tolerated dose of palbociclib and dexamethasone. Correlative studies, which are performed on pretreatment, day +1 and day +8 samples, include RB phosphorylation and FOXM1 expression as measures of palbociclib activity; CD19+ cell gene expression profiling of (1) p21 expression as an indicator of cell cycle activity, (2) S-Phase, Annexin V/Caspase 3 activation as indicators of proliferation and apoptosis and (3) Myb and Bcl-2 expression as indicators of dexamethasone sensitivity. Cohort 1 is currently enrolling. Once a maximum tolerated dose is established, an expansion cohort is planned. Clinical trial information: NCT03472573.
Phase 2, open-label study of pembrolizumab in children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) with slow early response (SER) to frontline chemotherapy: KEYNOTE-667.
Authors: Mauz-Körholz Christine , Kelly Kara M. , Keller Frank G. , Ramchandren Rod , Nahar Akash , Giulino-Roth Lisa 
Published: March 2020

TPS7567 Background: High risk for relapse is observed in cHL patients (pts) with SER to initial chemotherapy and organ toxicities may be higher following dose intensification. Methods: The phase 2 KEYNOTE-667 study will enroll 440 pts aged 3 to 17 (children) or 18 to 25 years (young adults) with newly diagnosed, confirmed stage IA, IB, or IIA cHL without bulky disease (Group 1 [low-risk]) or stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL (Group 2 [high-risk]); measurable disease; and performance status per Lansky Play-Performance Scale ≥50 (age ≤16 years) or Karnofsky score ≥50 (age >16 years). Pts will receive induction with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD; Group 1) or vincristine, etoposide/etoposide phosphate, prednisone/prednisolone, doxorubicin (OEPA; Group 2) for 2 cycles, then early response assessment by PET/CT/MRI. Pts with rapid early response (Deauville score 1-3) will receive standard therapy. Pts with SER (Deauville score 4-5) will receive consolidation with pembro 2 mg/kg Q3W up to 200 mg (children) or 200 mg Q3W (young adults) plus 2 cycles AVD (Group 1) or 4 cycles cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28; Group 2). PET/CT for late response assessment (LRA) will be performed after consolidation. After LRA, Group 1 pts with SER and Group 2 pts with Deauville score 4-5 will receive radiotherapy (RT). All pts will receive maintenance with pembro Q3W concomitantly with RT. Pembro will continue up to 17 administrations, with an option to stop after 24 weeks due to CR, or until progression, unacceptable toxicity, or withdrawal. The primary endpoint is ORR per Cheson 2007 IWG criteria by group in SER pts. Secondary endpoints are SERs with PET negativity after consolidation, 2-yr event-free survival (EFS), OS, and RT frequency and details by group, RERs with PET negativity after ABVD induction, 3-yr EFS by investigator, and OS by risk group, and serum TARC levels at screening in SERs by risk group. ORR with 95% CI will be estimated by Clopper-Pearson method. EFS and OS will be estimated by Kaplan-Meier method. Safety will be assessed in all treated pts. Clinical trial information: NCT03407144.
Phase I/II, open-label, 2-arm study to evaluate safety, tolerability, and clinical activity of GSK2857916 in combination with 2 standard-of-care (SoC) regimens in relapsed/refractory multiple myeloma: (DREAMM 6).
Authors: Costa Luciano J. , Quach Hang , Stockerl-Goldstein Keith , Augustson Bradley , Ferron-Brady Geraldine , Chopra Bikramjit , Moore Allie , Hudson Sophia , Zhou Jiangxiu , Bragulat Veronique , Talekar Mala Kiran , Opalinska Joanna 
Published: March 2020

TPS8053 Background: B-cell maturation antigen (BCMA) is a validated therapeutic target in Multiple Myeloma (MM). GSK2857916 is a humanized (IgG1) anti-BCMA monoclonal antibody conjugated to monomethyl auristatin-F via protease resistant maleimidocaproyl linker and produced in afucosylated form to enhance antibody-dependent cellular cytotoxicity. In FTIH study BMA117159, GSK2857916 was well tolerated and showed unprecedented clinical activity [ORR=60%; mPFS 7.9 months (95% CI, 3.1–not estimable)] as monotherapy in heavily pretreated MM patients. GSK2857916 in combination with SoC regimens, could potentially further improve outcomes for patients with relapsed/refractory (RR) MM. Methods: DREAMM 6 is a 2-part study: Part 1 (dose escalation) is evaluating safety and tolerability of 2 doses (2.5 mg/kg and 3.4 mg/kg) of GSK2857916, in combination with SoC regimens in two independent arms: Arm A with Lenalidomide/Dexamethasone, and Arm B with Bortezomib/Dexamethasone. Modified Toxicity Probability Interval design will guide dose escalation and RP2D of GSK2857916 in each arm for Part 2 (cohort expansion). Part 2 will confirm safety, evaluate clinical activity of GSK2857916 RP2D with either combination and collect pharmacokinetic information on GSK2857916, Lenalidomide and bortezomib. Up to 90 subjects previously treated with at least 1 prior line of therapy who have undergone autologous stem cell transplant or are transplant-ineligible will be enrolled; up to 24 in Part 1 and up to 66 in Part 2. Subjects in Arm A will continue combination treatment until progression, intolerance, consent withdrawal or death. Subjects in Arm B will receive up to 8 cycles of GSK2857916 in combination with Bor/Dex and then continue GSK2857916 monotherapy until progression, intolerance, consent withdrawal, or death. Enrolment on study started in October 2018 and is ongoing. Study funded by GlaxoSmithKline; drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. ClinicalTrials.gov Identifier: NCT03544281.
Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): A multicenter, randomized, phase III study (PERSEUS).
Authors: Sonneveld Pieter , Broijl Annemiek , Gay Francesca , Boccadoro Mario , Einsele Hermann , Blade Joan , Dimopoulos Meletios A. , Delforge Michel , Spencer Andrew , Hajek Roman , Schjesvold Fredrik , Lonergan Sarah , Smith Elena , Carson Robin L. , Crist Wendy , Garvin Wendy S. , Vermeulen Jessica , Moreau Philippe 
Published: March 2020

TPS8055 Background: DARA, a human, CD38-targeting, IgGκ monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory MM (RRMM), and in combination with standard-of-care regimens in RRMM and transplant-ineligible NDMM. Given the initial safety and efficacy observed with DARA plus VRd (D-VRd) in the safety run-in cohort of the ongoing phase 2 GRIFFIN study in TE NDMM pts, the phase 3 PERSEUS study will evaluate the efficacy and safety of D-VRd versus VRd alone in TE NDMM. Methods: This is an ongoing multicenter, open-label, randomized phase 3 study of D-VRd versus VRd alone in TE NDMM pts. Approximately 690 pts across Europe will be stratified by ISS stage and cytogenetic risk (high risk defined as presence of del17p, t[4;14], or t[14;16]) and randomized in a 1:1 ratio. All pts will receive VRd (V: 1.3 mg/m2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-21; d: 40 mg PO Days 1-4, 9-12) for 4 pre-transplant induction and 2 post-transplant consolidation cycles (all 28-d cycles), followed by R (10 mg PO Days 1-28) maintenance until progressive disease (PD). Pts in the DARA group will also receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W in maintenance Cycles 7+ until PD. After induction, pts will undergo melphalan 200 mg/m2 conditioning and autologous stem cell transplantation (ASCT). Pts in the DARA group who achieve sustained minimal residual disease (MRD) negativity (10–5 threshold; assessed by NGS) for 12 months after ≥24 months of maintenance will stop DARA but continue R maintenance until PD; upon loss of CR or MRD-negative status, pts will restart DARA treatment. All pts will receive preinfusion medications. The primary endpoint is progression-free survival (PFS). Secondary endpoints include MRD-negative rate, overall response rate, PFS on next line of therapy, overall survival, time to and duration of response, health-related quality of life, pharmacokinetics, immunogenicity, stem cell yield after mobilization, time to engraftment post-ASCT, and safety. Clinical trial information: NCT03710603.
The myeloma-developing regimens using genomics (MyDRUG) master protocol.
Authors: Auclair Daniel , Anderson Kenneth Carl , Avigan David , Bianchi Giada , Biran Noa , Chaudhry Maria , Cho Hearn J. , Furlong Maggie , Hofmeister Craig C. , Kansagra Ankit J. , Krishnan Amrita Y. , Larsen Jeremy Todd , Orloff Gregory Joshua , Vij Ravi , Voorhees Peter Michael , Yee Andrew Jenho , Ye Jing Christine , Zonder Jeffrey A. , Lonial Sagar , Kumar Shaji 
Published: March 2020

TPS8057 Background: Multiple myeloma (MM) is the second most prevalent blood cancer, representing approximately 1% of all cancers. Although overall survival has improved in recent years due to new approved agents, the vast majority of MM patients (pts) ultimately stop responding to treatment. Moreover, about a quarter of MM pts characterized as “high risk” experience limited benefit from existing treatments. Seminal genomic sequencing research efforts, such as the MMRF CoMMpass study, have highlighted that a large number of MM cases harbor potentially actionable oncogenic molecular alterations and published reports on small numbers of cases suggest that Precision Medicine (PM) interventions clinically targeting such actionable drivers may benefit MM pts. These results suggest that PM approaches in MM are possible and should be further studied clinically. To that end, we have launched MyDRUG, a master protocol aimed at developing new myeloma regimens based on individual pt’s genomics. Methods: This study is a Phase I-II, multicenter master protocol in functional high risk MM patients (i.e patients having progressed from baseline treatment within 18 months without maintenance or 3 years on maintenance) with 1-3 prior lines of therapy. Patients are screened for actionable genomic alterations on the CLIA-grade MI-ONCOSEQ platform. Patients with actionable alterations are assigned to the appropriate targeted agent used in combination with a backbone regimen ixazomib, pomalidomide and dexamethasone (IPd), whereas patients without such alterations go on an immune arm (see Table). Inclusion criteria include measurable disease (as measured by M-protein and FLC) and acceptable hematologic and metabolic functions. A maximum of 12 evaluable pts will be accrued onto the phase I portion of each arm and an additional 21 evaluable phase II pts will be accrued onto each arm for a total of 27 evaluable pts at the MTD combination dose. The primary objective of the study is to evaluate ORR per IMWG consensus criteria. Secondary objectives are to assess adverse events (AEs), progression-free survival, and overall survival (OS). Experimental correlative aims include assessing molecular or clonal response, molecular and immune signatures of resistance/response, MRD. Clinical trial information: NCT03732703. [Table: see text]
CANOPY-A: A phase III study of canakinumab as adjuvant therapy in patients with surgically resected non-small cell lung cancer (NSCLC).
Authors: Garon Edward B. , Ardizzoni Andrea , Barlesi Fabrice , Cho Byoung Chul , De Marchi Pedro , Goto Yasushi , Lu Shun , Paz-Ares Luis G. , Spigel David R. , Thomas Michael , Mookerjee Bijoyesh , Cazorla Arratia Pilar , Baum Jason , Lau Yi-Yang Yvonne , Zhu Zewen , Yang James Chih-Hsin 
Published: March 2020

TPS8570 Background: Overexpression of interleukin (IL)-1β has been described in solid tumors, including lung. IL-1β can promote angiogenesis, tumor invasiveness, and induce tumor-associated immunosuppression through myeloid-derived suppressor cell (MDSC) accumulation in tumors. Pre-clinical data has shown that IL-1β inhibition stably reduces tumor growth, by limiting inflammation and inducing the maturation of MDSCs into M1 macrophages. Canakinumab is a human monoclonal antibody with high affinity and specificity for IL-1β. Recently, it was found that canakinumab was associated with a significant and dose-dependent reduction in incidence and mortality from lung cancer based on CANTOS study. Methods: CANOPY-A is a phase III, randomized, double-blind, placebo-controlled study designed to evaluate efficacy and safety of adjuvant canakinumab versus placebo in patients with surgically resected NSCLC. This trial will enroll adult patients, with completely resected (R0) AJCC/UICC v.8 stages II−IIIA and IIIB (T >5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or neoadjuvant radiotherapy is not permitted. Approximately 1500 patients will be randomized 1:1 to receive canakinumab (200 mg Q3W, s.c) or placebo (Q3W, s.c.) for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, death, or loss to follow-up. Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region. The primary objective is disease-free survival, per investigator assessment. Secondary objectives include overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and patient-reported outcomes. Enrollment is ongoing. Clinical trial information: NCT03447769.
The selective personalized radioimmunotherapy for locally advanced NSCLC trial (SPRINT).
Authors: Ohri Nitin , Cheng Haiying , Jolly Shruti , Gadgeel Shirish M. , Cooper Benjamin Thomas , Shum Elaine , Halmos Balazs 
Published: March 2020

TPS8571 Background: Concurrent chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC) can cause significant toxicities, and disease recurrence after treatment is common. We previously demonstrated that a dose-painted radiotherapy approach provides excellent local disease control and has a favorable toxicity profile. Consolidation immunotherapy was recently shown to improve outcomes after chemoradiotherapy for LA-NSCLC, and pembrolizumab monotherapy is now a standard of care for patients with advanced high PD-L1-positive NSCLC. We hypothesize that dose-painted thoracic radiotherapy and immunotherapy without chemotherapy will be safe and effective for the treatment of biomarker-selected patients with LA-NSCLC. Methods: Patients with a new diagnosis of unresectable stage II or stage III NSCLC and performance status 0-1 will be enrolled on this phase II trial at one of three participating institutions. Twenty-five subjects with PD-L1 Tumor Proportion Score (TPS) of at least 50% will receive three cycles of induction pembrolizumab (200 mg every 3 weeks). Subjects then receive 20 fractions of dose-painted radiotherapy, where lesions with metabolic tumor volume exceeding 20 cc on FDG-PET receive a dose of 55 Gy, while smaller lesions receive a dose of 48 Gy. Subjects then receive 12 additional cycles of pembrolizumab. The primary endpoint is progression-free survival one year following study enrollment, which we hypothesize will be achieved for at least 65% of study subjects. Other endpoints include overall survival, distant metastasis-free survival, freedom from intrathoracic disease progression, adverse events, patient-reported outcomes, and physical activity metrics captured using wearable devices. In addition, we will explore markers of immune activation as prognostic factors. Approximately 38 patients with PD-L1 TPS below 50% will receive standard chemoradiotherapy and adjuvant therapy to serve as a contemporary comparison cohort. SPRINT is an innovative biomarker-driven study that explores a paradigm shift in the local and systemic therapy used to treat LA-NSCLC. This trial opened in August of 2018, and 5 subjects have been enrolled to date. Clinical trial information: NCT03523702.