Survival After Failure of Initial Therapy for Newly-Diagnosed or Relapsed/Refractory AML At An Academic Center: Subsequent Clinical Trial Vs. Not

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1497-1497
Author(s):  
Ravinder K Sandhu ◽  
Jack M. Lionberger ◽  
Megan Othus ◽  
John M. Pagel ◽  
Kathleen ShannonDorcy ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Salvage Therapy ◽  
Survival Benefit ◽  
Trial Participation ◽  
Therapeutic Trial ◽  
Trial Group ◽  
Newly Diagnosed ◽  
Data Set ◽  
Cell Counts ◽  
The Impact

Abstract Abstract 1497 Background: Many adult patients do not enter complete remission (CR) after therapy for acute myeloid leukemia (AML) and the physician must often give advice regarding continued anti-AML therapy in a clinical trial. Even with novel therapeutics and approaches, numerous publications suggest a probability of CR <20% in these patients. Considering the time investment, the possibility of toxicity, and the impact on quality of life, the “non trial” (i.e. supportive or palliative care) approach becomes a potentially attractive alternative for some patients. These factors are especially critical when the patient lives a considerable distance from the treating center. To better inform this decision-making process, we compared survival in two groups of patients who had each received therapy at the Seattle Cancer Care Alliance (outpatient) or University of Washington (inpatient) (SCCA/UW) without obtaining a CR. One group included those who subsequently elected to enroll in a clinical trial and did not achieve a remission (Trial group), and the other group included patients who subsequently decided to receive no further specific anti-leukemic therapy at the SCCA/UW (the Non-trial group). Methods: Patients were identified by database query, and when necessary confirmed by direct review of paper and electronic medical records. Our data set included patients arriving to the SCCA/UW between January 2008 and March of 2011. Patients selected for this study were those whose most recent therapy was given at SCCA/UW and was unsuccessful (no CR). The date this outcome was determined is called the “resistance date” (RD). We dated survival from RD in the Non-trial group and from the date on which the salvage treatment was started in the patients receiving therapy. As best we can tell, none of the Non-Trial patients received subsequent salvage outside the SCCA/UW (i.e., after returning home). Multivariate analysis was used to assess the effect on survival time of (a) Trial participation (yes or no), (b) age, (c) performance status (PS 0–1 vs. 2–4) at resistance date, (d) cytogenetics (unfavorable vs. favorable/intermediate), and (e) status at initial SCCA/UW visit (newly-diagnosed vs. secondary vs. relapsed vs. refractory). Results: 134 patients had their initial SCCA/UW therapy without obtaining CR. Sixty-four of these subsequently received unsuccessful salvage therapy at the SCCA/UW (the Trial group) and 70 did not (Non-trial group). Distribution of age (median 59), cytogenetic risk (60% unfavorable), and PS of 2 or higher (35%) was similar in both groups. Independent predictors of shorter survival were: PS 2–4 (HR 1.70, p=0.02), “unfavorable” cytogenetics (HR 1.77, p = 0.01), relapsed at initial SCCA visit compared to newly-diagnosed (HR 1.93, p = 0.03), and presence in the non-trial group (HR 3.20, p <.001). The unadjusted survival comparison is shown below and indicates an approximate 10 month median survival benefit for patients receiving salvage at SCCA (HR 2.68, p<.001). Conclusions: There is a survival benefit associated with receiving salvage therapy (Trial group) for adult AML at the SCCA/UW (and presumably similar centers) despite failure to achieve CR with this salvage therapy. This degree of benefit in a new therapeutic trial would likely lead to FDA approval. The seeming advantage may reflect a non-quantifiable bias leading to selection of “better” patients for trials, a closer follow-up of patients placed on trials, or a true survival benefit despite lack of CR. The latter might reflect a regimen's ability to lower malignant proliferation and/or improve functional cell counts. Despite the confounding, and recognizing that a randomized trial to address this issue is unlikely, it seems reasonable for a patient to attempt to participate in clinical trials of new AML salvage therapies, recognizing however, that factors other than survival may affect a given patient's decision. Disclosures: No relevant conflicts of interest to declare.

Impact of organ function based standard exclusion criteria in diffuse large b-cell lymphoma (DLBCL) patients: Who gets left behind?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14100-e14100
Author(s):  
Arushi Khurana ◽  
Raphael Mwangi ◽  
Grzegorz S. Nowakowski ◽  
Thomas Matthew Habermann ◽  
Stephen M. Ansell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Trial Participation ◽  
Newly Diagnosed ◽  
Organ Function ◽  
Exclusion Criteria ◽  
The Us ◽  
The Impact

e14100 Background: Only 3-5% of adult cancer patients in the US enroll in clinical trials. Patients with organ dysfunction are often excluded from clinical trials, regardless of specific drug metabolism or relative function of the organ. The ASCO and the US FDA recommend modernizing criteria related to baseline organ function and comorbidities. In hematological malignancies, often the disease itself is the reason for organ function derangement. In order to better inform clinical trial eligibility and improve participation in the future, we evaluated the impact of baseline organ function on the potential eligibility for clinical trial enrollment for real world patients with newly diagnosed DLBCL. Methods: Consecutive, newly diagnosed lymphoma patients were offered enrollment from 2002-2015 into the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence. This analysis is based on 1270 DLBCL patients receiving immunochemotherapy. Baseline organ function parameters were identified from the exclusion criteria for hemoglobin, absolute neutrophil count (ANC), platelet count, creatinine, and bilirubin reported in recent frontline trials in DLBCL (Table). Abstracted clinical labs from the MER were used to determine the percent of patients that would be excluded based on the criteria. Results: We determined that 11-23% of MER DLBCL patients receiving standard of care frontline therapy would have been excluded in the various trials utilizing baseline organ function alone (Table). Hemoglobin and renal function had the greatest impact on exclusion. Conclusions: Current national and international (phase II and III) trials are excluding up to 23% of patients from clinical trial participation based on organ function alone in DLBCL. These data will be useful in future clinical trial development to meet ASCO recommendations to increase trial accrual, while balancing the drug toxicities and patient safety. An online tool was developed based on these results to aid future trial development. [Table: see text]

scholarly journals Patient Income Level and Cancer Clinical Trial Participation

2013 ◽  
Vol 31 (5) ◽  
pp. 536-542 ◽  
Author(s):  
Joseph M. Unger ◽  
Dawn L. Hershman ◽  
Kathy S. Albain ◽  
Carol M. Moinpour ◽  
Judith A. Petersen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Universal Access ◽  
Participation Rate ◽  
Treatment Decision ◽  
Trial Participation ◽  
Lower Income ◽  
Clinical Trial Participation ◽  
Clinical Trial Results ◽  
The Impact

Purpose Studies have shown an association between socioeconomic status (SES) and quality of oncology care, but less is known about the impact of patient SES on clinical trial participation. Patients and Methods We assessed clinical trial participation patterns according to important SES (income, education) and demographic factors in a large sample of patients surveyed via an Internet-based treatment decision tool. Logistic regression, conditioning on type of cancer, was used. Attitudes toward clinical trials were assessed using prespecified items about treatment, treatment tolerability, convenience, and cost. Results From 2007 to 2011, 5,499 patients were successfully surveyed. Forty percent discussed clinical trials with their physician, 45% of discussions led to physician offers of clinical trial participation, and 51% of offers led to clinical trial participation. The overall clinical trial participation rate was 9%. In univariate models, older patients (P = .002) and patients with lower income (P = .001) and education (P = .02) were less likely to participate in clinical trials. In a multivariable model, income remained a statistically significant predictor of clinical trial participation (odds ratio, 0.73; 95% CI, 0.57 to 0.94; P = .01). Even in patients age ≥ 65 years, who have universal access to Medicare, lower income predicted lower trial participation. Cost concerns were much more evident among lower-income patients (P < .001). Conclusion Lower-income patients were less likely to participate in clinical trials, even when considering age group. A better understanding of why income is a barrier may help identify ways to make clinical trials better available to all patients and would increase the generalizability of clinical trial results across all income levels.

ONC201 in previously irradiated pediatric H3 K27M-mutant glioma or newly diagnosed DIPG.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3619-3619
Author(s):  
Sharon L. Gardner ◽  
Carl Johannes Koschmann ◽  
Rohinton Tarapore ◽  
Jeffrey C. Allen ◽  
Wafik Tharwat Zaky ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Single Agent ◽  
High Grade Glioma ◽  
Biologically Active ◽  
High Grade ◽  
Newly Diagnosed ◽  
Preclinical Models ◽  
Open Label ◽  
The Impact

3619 Background: ONC201 is a first-in-class DRD2 antagonist and ClpP agonist that has demonstrated promising activity in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 in recurrent H3 K27M-mutant glioma patients . The recommended phase 2 dose (RP2D) of 625mg ONC201 orally once a week has been established in adult patients as well tolerated and biologically active. ONC201 efficacy has been shown in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 have been reported in adult recurrent H3 K27M-mutant glioma patients. We report results from the first Phase I pediatric clinical trial of ONC201. Methods: This open-label, multi-center trial for pediatric H3 K27M-mutant glioma or non-biopsied DIPG employed a 3+3 dose-escalation and dose-expansion design with 6 arms. Arms A and E, which have completed accrual, determined the RP2D of ONC201 using oral capsule and liquid formulations in post-radiation pediatric H3 K27M-mutant glioma patients ONC201, respectively. Arm B aims to determine the RP2D for ONC201 in combination with radiotherapy in patients with newly diagnosed DIPG. Arms C and D aim to measure intratumoral ONC201 concentrations in midline glioma patients and the impact of ONC201 on H3 K27M DNA levels in CSF, respectively. Arm F was recently opened to study ONC201 as a single agent in patients with progressive H3 K27M-mutant tumors (excluding DIPG and spinal cord tumors) following radiotherapy. After determining the RP2D, a dose-expansion cohort will evaluate the safety, radiographic response, and activity of ONC201. Results: An RP2D of weekly 625mg ONC201 scaled by body weight as a capsule or in liquid formulation was established in the primary endpoints of arms A, B and E alone or in combination with radiation, without incidence of dose-limiting toxicity (DLT). Pharmacokinetic profiles were similar to those observed in adults (T1/2: 8.4h; Tmax: 2.1h; Cmax: 2.3ug/mL; AUC0-tlast: 16.4ug/mL), with similar exposure across body weights. Conclusions: ONC201 was well tolerated without DLTs at the same adult RP2D scaled by body weight as monotherapy or in combination with radiotherapy in pediatric H3 K27M-mutant glioma patients. Further investigation of ONC201 to treat H3 K27M-mutant glioma and DIPG is warranted. Clinical trial information: NCT03416530 .

scholarly journals Optimizing eligibility criteria and clinical trial conduct to enhance clinical trial participation for primary brain tumor patients

2020 ◽  
Author(s):  
Eudocia Q Lee ◽  
Michael Weller ◽  
Joohee Sul ◽  
Stephen J Bagley ◽  
Solmaz Sahebjam ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Response Assessment ◽  
Primary Brain Tumor ◽  
Trial Participation ◽  
Cooperative Groups ◽  
Clinical Trial Participation ◽  
Eligibility Criteria ◽  
Trial Conduct ◽  
The Impact ◽  
Clinical Trial Conduct

Abstract Building on an initiative to enhance clinical trial participation involving the Society for Neuro-Oncology, the Response Assessment in Neuro-Oncology Working Group, patient advocacy groups, clinical trial cooperative groups, and other partners, we evaluate the impact of eligibility criteria and trial conduct on neuro-oncology clinical trial participation. Clinical trials often carry forward eligibility criteria from prior studies that may be overly restrictive and unnecessary and needlessly limit patient accrual. Inclusion and exclusion criteria should be evaluated based on the goals and design of the study and whether they impact patient safety and/or treatment efficacy. In addition, we evaluate clinical trial conduct as a barrier to accrual and discuss strategies to minimize such barriers for neuro-oncology trials.

Stepwise examination of prostate clinical trials participation to reduce accrual barriers.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 157-157
Author(s):  
Dare Olatoye ◽  
Michael Anthony Carducci ◽  
Norma Kanarek
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Medical Oncology ◽  
Local Therapy ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Trial Participation ◽  
Therapeutic Trial ◽  
Clinical Trial Participation

157 Background: Adequate and representative enrollment in therapeutic clinical trials is important to an NCI cancer center. Clinical trial participation is a string of 6 sequential patient and physician decisions beginning with an available therapeutic trial to enrollment in the trial. Opportunities for participation may be lost at any one of these steps. The objective of this study was to calculate transitional probabilities that measure patient, especially minority patient, accrual to clinical trials at the Sidney Kimmel Comprehensive Cancer Center and to describe the barriers for those dropping out at each step. Methods: Records for “first visit” medical oncology patients seen by three SKCCC physicians from January to April 2010 were abstracted. Prostate cancer case reports from the hospital cancer registry and a medical record review provided age, race, Hispanic ethnicity, place of residence, tumor characteristics, and prior treatment history. At each transition step, we calculated the proportion of patients who remained enrollable. Results: Overall, prostate cancer clinical trial participation was 17% (16/94). Minority accrual was similar to Caucasian accrual at 19% and 17% , respectively. Retention at each step of trial participation was highest for “discussed” (98%), “enrolled” (94%), “eligibility” for available trials (79%), and “consented” (71%). Two bottlenecks were qualitatively identified: “trial availability” (65%) and “patient interest” (51%). Forty-two percent of those for whom there was no trial available were older than 70 years and 33% were patients with rising PSA after local therapy and hormone-naïve. The “patient interest” step was shaped primarily by disinterest due to distance to SKCCC (83%). Conclusions: For prostate cancer patients, recruitment to medical oncology clinical trials is robust. Minority patients however are only 17% of all patients seen and half drop out when no trial is available and half of those remaining judged distance to be a problem (hence, no interest). This study approach has clarified which factors are likely to be barriers to participation and is likely useful to making adjustments that can reduce identified barriers by adding to trial portfolio as an example.

Increasing participation in breast cancer research: (INSPIRE-BrC).

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 53-53
Author(s):  
Brandi Robinson ◽  
Sandra M. Swain
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Primary Outcome Measure ◽  
Test Method ◽  
Trial Participation ◽  
Lower Survival Rate ◽  
Black Patients ◽  
Clinical Trial Enrollment ◽  
The Impact

53 Background: Increasing black patients’ participation in cancer clinical trials is particularly important because of the population’s lower survival rate. Accrual to clinical trials remains low among the general population (1 to 3%), with recruitment of blacks the lowest of all groups at 0.5 to 1.5%. Clinical trials are key to developing new methods to prevent, detect, and treat cancer. INSPIRE-BrC aims to increase trial participation rates among black patients with breast cancer and examine the relationship between the intervention and attitudes/beliefs on the decision to participate. Methods: A sample size of 123 black patients with breast cancer at five MedStar sites will view a 15 minute, culturally tailored video about clinical trials, which targets six cultural and attitudinal barriers to participation. A pre-test/post-test method is used to determine the impact of the video on three variables — likely participation in therapeutic clinical trials; attitudes toward therapeutic clinical trials (assessed based on the 6 barriers); and actual trial enrollment. Expected Findings: We hypothesize that the intervention will increase clinical trial enrollment compared to our 2012 clinical trial enrollment baseline rate of 6% (22/384) for black patients with breast cancer in five MedStar hospitals. The primary outcome measure is the proportion of black patients with breast cancer who agree to participate in a therapeutic clinical trial among those who sign consent to INSPIRE-BrC. Study findings have the potential to increase patient recruitment as a promising tool for rapid dissemination of a theory-driven, evidence-based model to enhance clinical trial accrual among black patients with cancer. [Table: see text]

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