Children with life-threatening conditions, such as cancer, are often candidates for clinical trials. What are they? Which factors should parents weigh in determining whether enrolling in one is a good option for their child? Dr. Steven DuBois, director of the Advancing Childhood Cancer Therapies Clinic at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, answers questions about clinical trials.
What are clinical trials? Why are they important?
Clinical trials are systematic, scientific investigations of new drugs or therapies for a specific disease. Through clinical trials, we have taken many fatal pediatric cancers and turned them into diseases that now have cure rates of over 90 percent. Although we still want to improve those cure rates, research is now increasingly focused on making treatments more tolerable and reducing late effects of therapy.
In other pediatric cancers, we are not doing as well, so our goal is to improve cure rates for patients with a poor prognosis. After decades of focusing on various chemotherapy agents and combinations to improve outcomes, much of today’s focus is on precision medicine, immunotherapies and other novel approaches that we hope will deliver less toxic and more effective treatment than chemotherapy.
What is a Phase 1 trial? Phase 2? Phase 3?
When we hear about a new drug or combination that has not yet been tested in children but shows promise in laboratory research or adult trials, we must first determ…
B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Genomic alterations in B-ALL are essential for disease diagnosis, prognosis, and treatment. We performed integrated genomic analysis on 136 pediatric B-ALL patients using the CHOP Comprehensive Hematological Cancer NGS Panel along with conventional cytogenetic studies. The panel interrogates 118 cancer genes for sequence and copy number variants (CNV) and 110 genes for known and novel fusions. Clinically significant genomic changes were identified in 89.7% of patients.
In conclusion, our study demonstrated that a clinically relevant regimen of systemic and intrathecal methotrexate induces persistent deficits in spatial pattern memory, visual recognition memory and executive function, lasting at least 8 weeks after the last injection. The mechanisms behind methotrexate-induced deficits are likely multifactorial and may relate to suppression of neurogenesis, alterations in neuroinflammation and microglial activation, and structural changes in the corpus callosum.
PMID: 29990472 [PubMed – as supplied by publisher]
Publication date: August 2018Source: Cancer Genetics, Volumes 224–225Author(s): Μ. Αmpatzidou, S.I. Papadhimitriou, G. Paterakis, D. Pavlidis, Κ. Tsitsikas, I.V. Kostopoulos, V. Papadakis, G. Vassilopoulos, S. PolychronopoulouThe prognostic significance of the ETV6/RUNX1-fusion and of the accompanying aberrations is disputable; whether co-existing sub-clones are responsible for delayed MRD-clearance and thus, moderate outcome, remains to be clarified. We studied, in a paediatric cohort of 119 B-ALLs, the relation between the ETV6/RUNX1 aberration and the co-existing subclones with (a) presenting clinic…
Publication date: 14 May 2018Source: Cancer Cell, Volume 33, Issue 5Author(s): Junne Kamihara, Akiko ShimamuraIKZF1 plays an essential role in lymphopoiesis, and somatic IKZF1 variants in acute lymphoblastic leukemia (ALL) are associated with poor prognosis. In this issue of Cancer Cell, Churchman et al. add to the list of leukemia predisposition genes with the identification and characterization of germline IKZF1 variants in childhood ALL.
Publication date: 14 May 2018Source: Cancer Cell, Volume 33, Issue 5Author(s): Michelle L. Churchman, Maoxiang Qian, Geertruy te Kronnie, Ranran Zhang, Wenjian Yang, Hui Zhang, Tobia Lana, Paige Tedrick, Rebekah Baskin, Katherine Verbist, Jennifer L. Peters, Meenakshi Devidas, Eric Larsen, Ian M. Moore, Zhaohui Gu, Chunxu Qu, Hiroki Yoshihara, Shaina N. Porter, Shondra M. Pruett-Miller, Gang WuSummarySomatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations res…
Induction chemotherapy results in high remission rate in high risk (HR) and very high risk (VHR) childhood acute lymphoblastic leukemia (ALL), but is associated with significant morbidity [1,2]. HR B-ALL is defined as: white blood cell count (WBC) ≥50,000/µL or age ≥10 years (National Cancer Institute (NCI) criteria) at presentation, or/and central nervous system (CNS) positive leukemia, or testicular leukemia [3–5]. Patients who are>13 years or experience induction failures; and/or if the leukemia blasts harbor mixed-lineage leukemia gene (MLL) rearrangements or intrachromosomal amplification of chrom…
Publication date: October 2018 Source:Cancer Genetics, Volumes 226–227 Author(s): LB Baughn, MM Meredith, L Oseth, TA Smolarek, B Hirsch Acute lymphoblastic leukemia (ALL) represents the most common childhood malignancy. Although survival for pediatric B-ALL has approached 90%, variability in outcome among and within cytogenetically defined subgroups persists. While G-banding and fluorescence in situ hybridization (FISH) have been used to characterize leukemic clones, there is added value of chromosomal microarray and next generation sequencing in screening genome-wide for copy number aberrations, copy neutral loss …
Conclusions: We found that telomere attrition may be
related to the pathogenesis of childhood ALL, irrespective to TERT variants.
PMID: 29936725 [PubMed – in process]
International Journal of Cancer,Volume 0, Issue ja, -Not available-.
Acute lymphoblastic leukemia (ALL) represents the most common childhood malignancy. Although survival for pediatric B-ALL has approached 90%, variability in outcome among and within cytogenetically-defined subgroups persists. While G-banding and fluorescence in situ hybridization (FISH) have been used to characterize leukemic clones, there is added value of chromosomal microarray and next generation sequencing in screening genome-wide for copy number aberrations, copy neutral loss of heterozygosity and nucleotide variations.