Our Clinical Trials Continually updated listing of our clinical trials for pediatric cancers 
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Our pediatrics team is at the forefront of developing new treatments for a variety of pediatric cancers, including leukemias, lymphomas, brain tumors, neuroblastoma, bone cancer, and retinoblastoma, among others. We are at the leading edge of both basic science and clinical research in investigating the causes of and new treatments for pediatric cancers.
Our research team includes specialists who focus solely on pediatric cancers, including medical and radiation oncologists and radiologists. We have pioneered many developments in the treatment of pediatric cancers over the past several decades, including bone marrow transplants, limb-sparing surgery for bone cancer, and immunotherapies. In addition, we have conducted extensive research on the long-term side effects of treatments for pediatric cancer, following patients for decades after they have been cured.
Our extensive involvement in the Children's Oncology Group and our leadership of the recently established Pediatric Oncology Experimental Therapeutic Consortium (POETIC) ensures the bidirectional flow of information between the Pediatrics Disease Management Team (DMT) and national cooperative efforts.
Among our recent research accomplishments:
Detection, Diagnosis, and Prognosis
From our repository of carefully annotated tumor samples for each childhood malignancy, our Pediatrics DMT has conducted comprehensive analyses of genes expressed in some of the major solid tumors affecting children. These studies have identified distinctive gene expression signatures for osteogenic sarcoma, Ewing's sarcoma, and neuroblastoma, and delineated, within each tumor type, clusters of genes differentially expressed by disease subsets differing in histologic grade, potential for metastasis, and responsiveness to current therapies.
- In high-risk neuroblastoma, these studies have defined genes associated with overexpression of N-myc and polymorphisms affecting responses to antibody-targeted therapies -- for example, polymorphisms of the FcG receptor alpha that limit the antitumor activity of the GD2-specific MAb 3F8. We are engineering the antibody to permit binding to each polymorphism of the FcR. J Clin Oncol. 2006;24:2885-2890. [PubMed Abstract]
- In patients with osteogenic sarcoma, we found that expression of the WNT family member LRP5 correlates with the presence of metastases and shorter time to progression, while the absence of detectable telomere maintenance mechanisms favorably influences the course. This latter observation was followed up by mechanistic studies providing evidence for a possible role of Wnt signaling in the pathobiology and progression of osteogenic sarcoma.
Novel Therapeutic Approaches
The Pediatrics Disease Management Team recently developed several promising new agents and chemoradiotherapy regimens for the treatment of childhood malignancies and several adult cancers. Examples include:
- The N7 regimen, which has combined intensive alkylator-based chemotherapy with GD2-specific MAb-based immunotherapy to significantly improve prognosis for patients with stage 4 neuroblastoma.
- The use of the anti-GD2 MAb 3F8 for the treatment of neuroblastoma and a proportion of osteogenic sarcomas.
- The introduction of a new gp96-specific MAb 8H9 for the detection and treatment of central nervous system gliomas and sarcomas of bone and muscle, respectively.
- Initial demonstration of the effectiveness of intrathecal immunotherapy with radioconjugated 3F8 and/or 8H9 for the treatment of leptomeningeal metastases of Ag (+) tumors.
- Demonstration in a multicenter collaborative study of the therapeutic activity of clofarabine in the treatment of refractory acute lymphoblastic leukemia. [PubMed Abstract]
- Irinotecan as a primary treatment for refractory rhabdomyosarcoma. J Clin Oncol. 2006;24:1917-1923.
- In addition, preclinical trials of beta-glucan as an adjunct to potentiate the antitumor activity of the monoclonal antibodies rituximab and 3F8 in the treatment of CD20+ lymphomas and GD2+ neuroblastomas and lung tumors, respectively, have been completed, as well as studies of the adoptive transfer of WT1 peptide-specific T cells for the treatment of refractory childhood leukemias, Wilms' tumor, and desmoplastic small round cell tumors. These approaches are now being introduced into clinical trials. Leuk Res. 2005;29:679-683. [PubMed Abstract]
- Our investigators are leading national efforts evaluating new treatments for bone sarcomas. We have also developed an algorithm to manage local recurrence based on time to recurrence and the presence of metastases. We are leading a new clinical trial to assess the bisphosphonate pamidronate as both an antineoplastic and bone-protective agent; the rationale comes from preclinical and clinical studies of bisphosphonates in other cancers and from our identification of genes of the osteoclastic pathways as being highly upregulated. A large cooperative study in osteogenic sarcoma showed an interaction between the biologic agent muramyl tripeptide and ifosfamide treatment; the two agents appeared most effective in combination, but the interaction will need further study to untangle an unexpected interaction between them. The intensive P6 protocol resulted in a high event-free survival rate (82 percent at four years) for those with locoregional disease and large primary tumors at diagnosis, but three of the patients developed secondary malignancies. Cancer. 2006;107:1607-1616. [PubMed Abstract]; J Clin Oncol. 2005;23:2004-2011. [PubMed Abstract]
- Our current institutional approach to Ewing sarcoma evaluates the addition of rapamycin (sirolimus) both as adjuvant maintenance therapy following P6 chemotherapy for patients with localized disease, and also as part of our allogeneic bone marrow transplantation regimen for patients at high risk of recurrence. The rationale for an allogeneic transplant approach to this disease is twofold: (a) in our experience, autologous stem-cell collections are commonly contaminated with the specific fusion transcript sequences of known tumor translocations, and (b) studies have suggested that sarcoma translocation products may be a target for T cell-mediated immune responses. In the transplant setting, we are seeking to recruit a graft-versus-host reaction to exploit its potential antitumor effect. The rationale for the inclusion of rapamycin includes data indicating the centrality of mTOR in the translocation EWS/FLi-1 and EWS/WT transcripts, and rapamycin's capacity to inhibit the translation of these fusion genes in vitro and inhibit growth of ES xenografts in vivo.
- To ground our therapeutics development program on as solid a biological basis as possible, the Pediatrics DMT received funding for an interactive multidisciplinary program of research into the genetics, molecular pharmacology, immunology and experimental therapy of malignancies of the developing nerve, bone, and muscle in children. We are seeking the identification, functional analysis, and targeted therapeutic modification of genes and gene products uniquely or differentially expressed by developmental malignancies of childhood. Individual projects focus on (a) identifying distinctive signatures of gene expression that define therapeutically relevant subclasses of these developmental tumors, and identifying genes and pathways that provide potential targets for drug and immune-based therapy by virtue of their differential expression or altered function; (b) evaluating the function of the unique fusion genes that characterize Ewing sarcoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor, identifying their targets, and characterizing the alterations in gene expression and tumor cell function associated with their inhibition; and (c) immune-mediated strategies for tumor targeting of toxic ligands or sensitized T cells.
Survivorship Initiatives
- We are studying the long-term, health-related outcomes of survivors of childhood cancer. We have been especially interested in the effects of chemotherapy and radiation therapy on physical growth, endocrine function, and reproductive outcomes in this population. The goals of these studies of late effects have been to characterize the prevalence and natural history of delayed toxicities, to develop the most efficacious and safe intervention strategies to ameliorate or prevent late complications, to extend our understanding of their pathogenesis, and ultimately to provide critical data to inform the development of new front-line cancer therapies that will result in the highest cure rates but with minimum toxicity.
- We recently completed a National Cancer Institute (NCI)-funded study looking at premature ovarian failure among female survivors who are participants in the Childhood Cancer Survivor Study. Our investigators are also conducting an NCI-funded study of risk factors for cardiovascular disease and the effectiveness of lifestyle interventions on cardiorespiratory fitness. We are also conducting an NCI-funded study via the Childhood Cancer Survivor Study, a 26-institution cohort study of 14,000 long-term survivors, to examine the use of screening mammography by female survivors.
- Other NCI-funded survivorship studies in children are being conducted to examine the psychosocial and behavioral aspects of cancer survivorship in adolescents. Memorial Sloan-Kettering is participating in a multi-institutional NCI-funded study of a Web-based smoking cessation intervention for childhood cancer survivors.
- Using data from the Childhood Cancer Survival Study, our researchers demonstrated that nearly half of adult survivors of childhood cancer have at least one moderate to severely diminished aspect of health status. In a follow-up study of this finding, they showed that 30 years after cancer diagnosis, 73 percent of survivors had at least one chronic health condition. N Engl J Med. 2006;355:1572-1582. [PubMed Abstract]
