Literature Scan
Overly Restrictive Clinical Trial Exclusion Criteria May Block Patients From Receiving Effective Therapy
Many clinical trials exclude patients with comorbidities , active or recent malignancies , organ dysfunction , or poor performance status , meaning that clinical trials typically enroll the “ Olympic athletes of patients ,” according to clinical trial researchers who spoke with ASH Clinical News about clinical trials ’ eligibility criteria in a recent feature article (“ Who ’ s In and Who ’ s Out ?”, December 2016 ). Such stringent criteria might limit “ unfit ” patients ’ access to potentially beneficial investigational therapies , according to a study published in Leukemia .
“ Only 3 to 5 percent of patients with cancer treated in the United States enroll in clinical trials ,” authors , led by Guillermo Montalban Bravo , MD , from the Department of Leukemia at the University of Texas MD Anderson Cancer Center , wrote , with strict clinical trial eligibility criteria likely playing a role in these low participation rates . [ The authors wanted ] to determine whether patients who were excluded from new therapeutic intervention studies [ could be enrolled ] within a monitored clinical trial safely , and whether they would derive benefit .
To test this concept , Dr . Montalban Bravo and investigators designed a clinical trial for patients with acute myeloid leukemia ( AML ) and myelodysplastic syndromes ( MDS ) who would be considered unfit for traditional clinical trials . Patients were treated with the hypomethylating agent azacitidine or the histone deacetylase inhibitor vorinostat – both of which have demonstrated an acceptable toxicity profile in previous clinical trials .
Patients (> 17 years old ) were included if they had at least one of the following :
• serum creatinine ≥2 mg / dL
• Survival : if 60-day survival was unlikely (< 5 %) to be ≥20 % compared with the historical group
• Response : if complete response ( CR ) was unlikely (< 10 %) compared with the historical group
• Toxicity : if the rate of grade ≥3 adverse events ( AEs ) were > 20 % at any time
The initial exploratory study included 30 patients with previously untreated AML ( n = 14 ; 47 %) and MDS ( n = 16 ; 53 %) who were consecutively enrolled at the University of Texas MD Anderson Cancer Center between
AML is swarming with challenges
• total bilirubin ≥2 mg / dL
• an Eastern Cooperative Oncology Group Performance Status of 3-4
• ineligibility to participate in a protocol of higher priority
Patients were excluded if they :
• had favorable cytogenetic abnormalities , such as inv ( 16 ), t ( 16 ; 16 ), t ( 8 ; 21 ), or t ( 15 ; 17 )
• received prior anti-leukemic therapies
The researchers also closely monitored patients for potential toxicity and response , and the study protocol included the following stopping rules :
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Impact of disease
• Acute myeloid leukemia ( AML ) is the most common type of leukemia in adults , accounting for approximately 25 % of leukemia diagnoses , with an estimated 19,950 new cases in the United States this year 1 , 2
• The 5-year survival rate in patients with AML is about 26 % 1
• An estimated 10,430 patients will die from AML this year 1
AML evolves rapidly because of its polyclonal and heterogeneous features , contributing to the clinical challenges of this disease 3
• As indicators of prognosis , cytogenetic and molecular mutation testing are recommended by the National Comprehensive Cancer Network ® ( NCCN ® ) at diagnosis 4
• Evaluation of molecular mutations may be important for risk assessment and prognosis to help guide treatment decisions 4