|Protocol||Trial Name and Objective|
Reduced Burden of Oncologic Therapy in Advanced B-cell Lymphoma (REBOOT ABLY) in Children, Adolescents and Young Adults with CD20+ Mature B-Cell Lymphoma
To safely reduce the burden of therapy in children, adolescents and young adults with mature B-NHL by reducing the number of intrathecal (IT) injections by the introduction of IT Liposomal Cytarabine (L-ARA-C, [Depocyt®]) and reducing the dose of anthracyline (doxorubicin) in good risk patients with the addition of rituximab to the FAB chemotherapy backbone (Immunochemotherapy).
1.1 To determine if the addition of intrathecal ([IT] [Depocyt®]) and reduction of standard IT dosing and the reduction of anthracycline exposure (doxorubicin) (60%) within the ANHL01P1 FAB/LMB B4 + Rituximab chemoimmunotherapy backbone in children, adolescents and young adults with good risk CD20+ mature B-NHL (Stage I and II unresected and Stage III/IV with LDH < 2 UNL) will result in similar outcomes compared to historical controls (Subgroup I).
1.2 To determine the safety and efficacy of reduction of IT therapy and substitution with L-ARA-C (Depocyte®) within ANHL01P1 FAB/LMB Group C1 plus rituximab chemotherapy backbone in children, adolescents and young adults with advanced risk de-novo mature B-NHL (Group C BMCNS) (Subgroup II).
1.3 To measure the change in cardiac biomarkers, cardiac troponin T (cTnT) and N-terminial pro-brain natriuretic peptide (NT-proBNP) and echocardiograms after doxorubicin treatment in children, adolescents and young adults with CD20+ mature B-NHL.
1.4 To measure the change in CSF minimal residual disease (MRD) pre and post administration of L-ARA- C in children, adolescents and young adults with CD20+ CNS mature B-NHL.
1.5 To measure CSF rituximab levels after systemic rituximab administration in children, adolescents and young adults with CD20+ mature B-NHL.
1.6 To further define the molecular, genetic, cytogenetics and proteomic characteristics of children, adolescent and young adults with CD20+ mature B-NHL.
Sun Protection and Skin Surveillance: Beliefs and Behaviors of Childhood Cancer Survivors
To establish the prevalence and correlates of skin cancer prevention and surveillance behaviors among CCS using depth interviews and survey research.
Targeted Genomic Analysis of Human Cancers
The purpose of this study is to identify potentially "actionable" genomic alterations in cancers using next-generation sequencing technology, with a focus on rare cancers and cancers for which there is limited standard therapy. The overall hypothesis of this protocol is that actionable mutations are present in a significant subset of patients with cancers for which there is no effective curative therapy. To test this hypothesis, the aims of this study are as follows:
1.1. To obtain blood and tumor tissue for next-generation sequencing and determine the frequency of finding genomic alterations for which there are clinically available (commercially or research based) targeted therapies. Treating clinicians will be provided with relevant validated mutation data for treatment or referral of the patient to pertinent studies.
1.2. To collect clinical outcomes of patients for which sequencing has been performed.
1.3. To obtain whole tumor genome data for data storage and future computational analysis and correlation with clinical data.
1.4. To obtain tumor tissue for development of future in vitro and in vivo cancer models.
COG-ACNS0332: Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients
1. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/PNET patients.
2. To determine whether Isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients.
3. To compare residual disease response to radiation alone versus radiation plus carboplatin.
4. To identify molecular prognostic indicators suitable for patient stratification in future trials.
5. To evaluate the HRQOL during phases of active treatment specific to treatment modalities.
6. To describe the neuropsychological functioning of the study population and to evaluate the relationship
between neuropsychological status and health related quality of life.
COG ACNS0831: Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients with Newly Diagnosed Ependymoma Ages 1 to 21 years
1. To determine the event free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with post-operative conformal radiation therapy (cRT) and then randomized to receive or not receive four cycles of post radiation maintenance chemotherapy with vincristine, cisplatin, etoposide and cyclophosphamide (VCEC).
2. To estimate the EFS and OS of children with incompletely resected ependymoma who are unable to achieve a complete response (CR) by a) post-operative induction chemotherapy or by b) second surgery who will then be non-randomly assigned to cRT followed by four cycles of maintenance chemotherapy (VCEC)
3. To further evaluate the EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second resection or children who achieve a CR to short course induction chemotherapy following first surgery.
COG AHEP0731: Treatment of Children with All Stages of Hepatoblastoma
Stage I hepatoblastoma (non-pure fetal histology [PFH]), non-small cell undifferentiated [SCU]) and Stage II (non-SCU) is a highly curable disease with 2 cycles of adjuvant cisplatin, 5-fluorouracil, and vincristine (C5V).
The addition of doxorubicin to the chemotherapy regimen of C5V for children with intermediate-risk hepatoblastoma will be feasible and associated with acceptable levels of toxicity.
The use of vincristine and irinotecan in an upfront window for children with high-risk, metastatic hepatoblastoma will improve the response rate in this group of children.
Referral for orthotopic liver transplant (OTL) is feasible in a cooperative group setting in children with hepatoblastoma designated as potentially unresectable following central surgical review and staging according to the PRE TEXT (Pretreatment Extent of Disease) grouping system.
1.2 Primary Aims
To estimate the EFS in children with Stage I (non-PFH, non-SCU) and Stage II (non SCU) hepatoblastoma treated with surgical resection followed by 2 cycles of C5V.
To determine the feasibility and toxicity of adding doxorubicin to the chemotherapy regimen of C5V for children with intermediate-risk hepatoblastoma.
To estimate the response rate to vincristine and irinotecan in previously untreated children with high-risk, metastatic hepatoblastoma.
To determine whether timely (between diagnosis and end of second cycle of chemotherapy) consultation with a treatment center with surgical expertise in major pediatric liver resection and transplant can be achieved in 70% of patients with potentially unresectable hepatoblastoma.
To foster the collection of tumor tissue and biologic samples to facilitate translational research and to provide data that may aid in risk-adapted approaches for subsequent clinical trials.
COG ACNS1022: A Phase II Randomized Trial of Lenalidomide (NSC # 703813, IND # 70116) in Pediatric Patients with Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas
1. To determine the objective response rate of children with recurrent, refractory or progressive juvenile astrocytomas and optic pathway gliomas who are treated with low-dose (20 mg/m2/dose) or high dose (115 mg/m2/dose) lenalidomide.
2. To estimate the event free survival of these patients when treated with lenalidomide
3. To correlate pharmacokinetics with objective response
4. To evaluate toxicities of long term lenalinomide use
COG ACCL0934:A Randomized Trial of Levofloxacin to Prevent Bacteremia in Children Being Treated for Acute Leukemia (AL) or Undergoing Hematopoietic Stem Cell Transplantation (HSCT)
1. To determine if levofloxacin given prophylactically during periods of neutropenia to patients being treated for AL or undergoing SCT will decrease the incidence of bacteremia
2. To determine the effect of prophylaxis on the incidence of F+N, severe infection and death from bacterial infection
3. Assess safety, with specific focus on musculoskeletal disorders
4. Assess impact on bacterial resistance
COG ACNS1123: Phase 2 Trial of Response-Based Radiation Therapy for Patients with Localized Central Nervous System Germ Cell Tumors (CNS GCT)
1. To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole ventricular field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young adults (ages 3 to Ü 21 years) with localized non-
germinomatous germ cell tumor (NGGCT) who have a magnetic resonance imaging (MRI) and tumor marker criteria (CSF and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with negative tumor markers who undergo a second-look surgery and are found to have only mature teratoma, residual scar or fibrosis and fit the definition of CR/PR after second-look surgery.
2. To determine, as measured by the 3-year PFS rate and patterns of failure, whether simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating children and young adults (ages 3 to Ü 21 years) with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCG Â) Ü50 mIU/ml
3. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (Germinoma) using the ALTE07C1 protocol. This objective will be assessed independently for the two strata.
4. To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated with 30.6Gy WVI and involved field focal (IFR) boost to 54Gy.
5.To estimate the PFS and OS distributions of
localized germinoma patients who present with
a) serum and/or CSF hCGÂ Ü50mIU/ml and b) serum and/or CSF hCG
Â> 50mIU/ml and Ü100mIU/ml.
COG ANHL12P1 A Randomized Phase II study of Brentuximab Vedotin (NSC# 749710) and Crizotinib (NSC# 749005) in Patients with Newly Diagnosed Anaplastic Large Cell Lymphoma (ALCL) IND #117117
1. To determine the
tolerability of brentuximab vedotin given in combination with
standard chemotherapy (ALCL99) and to determine the tolerability of crizotinib
given in combination with chemotherapy (ALCL99).
To estimate the Event Free Survival of Arm Brentuximab and standard chemotheray and Crizotinib and standard chemotherapy and contrast these to historical control data.
3. To determine the prognostic significance of minimal disseminated
disease (MDD) at diagnosis and minimal residual disease (MRD)
as measured by RT - polymerase chain reaction (PCR)in peripheral blood
COG ACNS1221: A Phase II Study for the Treatment of Non-Metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age
1. Estimate of the PFS distribution for patients 0-<4 years of age with M0 desmoplastic medulloblastoma (nodular desmoplastic or medulloblastoma with extensive nodularity) treated with the modified HIT SKK regimen (excluding the use of intraventricular methotrexate).
2.Evaluate the feasibility of a rapid central pathology screening review for treatment allocation according to histology and assess agreement between institutional and central pathology review diagnoses as well as among central pathology review diagnoses.
3.Prospectively evaluate the molecular profile of ND/MBEN medulloblastoma in young children.
4. Monitor and describe the neurocognitive and adaptive functioning of young children with ND/MBEN medulloblastoma treated on this protocol using the ALTE07C1 protocol.
Childrens Oncology Group ARST1321:Pazopanib Neoadjuvant Trial In Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib (NSC# 737754, IND# 118613)
1.1.1 To identify the dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric and adult patients newly diagnosed with unresected intermediate- and high-risk NRSTS.
1.1.2 To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative chemoradiation versus preoperative
chemoradiation alone for potentially resectable > 5 cm, Grade 3 intermediate to high risk chemotherapy-sensitive NRSTS in the Phase II portion of the study for this cohort. 1.1.3 To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for potentially resectable intermediate to high risk adult and pediatric NRSTS in the Phase II portion of the study for this cohort (using a Phase II decision rule to go onto the Phase III portion of the study).
1.1.4 To compare the rates of event-free survival (EFS) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for localized intermediate to high risk adult and pediatric NRSTS in the Phase III portion of the study for this cohort if the Phase II decision rule is passed.
1.2 Secondary Objectives
1.2.1 To estimate the rates of local failure, regional failure, distant metastasis free survival, disease-free survival, and overall survival with the addition of pazopanib to preoperative chemoradiation or preoperative radiation in intermediate to high
risk adult and pediatric NRSTS.
1.2.2 To compare the pattern of recurrence (local, regional and distant) between preoperative chemoradiation or radiation with the addition of pazopanib for adult and pediatric NRSTS. 1.2.3 To define the toxicities of ifosfamide and doxorubicin chemotherapy and radiation
when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.
1.2.4 To define the toxicities of preoperative radiotherapy when used in combination with pazopanib in intermediate to high risk adult and pediatric NRSTS.
Childrens Oncology Group-ANBL1232
Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients with Non-High-Risk Neuroblastoma
1.To eliminate therapy as the initial approach for infants < 12 months of age with small INRG Stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%.
2.To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favorable biology (histologic and
genomic features) while maintaining an OS of 99%.
3.To achieve a 3-year OS of > 81% for infants < 18 months of age with INRG Stage
Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm.
4.To describe the time to intervention or tumor progression, type of intervention and site of progression for patients with localized neuroblastoma who experience
progression after an initial period of observation.
5. To characterize the pharmacokinetic profile of the chemotherapeutic agents
carboplatin and etoposide in patients with Stage Ms disease.
6.To define the genomic profile of tumors from patients with non-high-risk
neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection.
7.To describe the histology of tumor specimens obtained at the time of subsequent biopsy or surgical resection.
8.To determine the salvage rate (OS) of patients with tumor relapse or disease progression.
9.To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the
degree of surgical resection.
10.To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumors following observation or chemotherapy
AALL1231: A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239; IND# 58443) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy)
1 To compare EFS in patients with newly diagnosed T-ALL and T-LLy who are randomized to a modified ABFM backbone versus bortezomib plus the modified ABFM backbone.
2.To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy based on the results of UKALL 2003, which includes a dexamethasone-based Induction, additional doses of pegaspargase (PEG-ASP) during Induction and Delayed Intensification (DI), and dexamethasone pulses during Maintenance therapy
3. To determine if prophylactic cranial radiation therapy (CRT) can be safely and effectively eliminated in the 85-90% of T-ALL patients classified asstandard or intermediate risk.
4.To determine the proportion of EOC MRD ? 0.1% T-ALL patients who become MRD negative (undetectable by flow cytometry) after intensification of chemotherapy, using three high risk (HR) BFM blocks, and to compare EFS between the patients who become MRD negative after the three HR BFM blocks and continue on chemotherapy with those who continue to have detectable MRD and are eligible for other treatment strategies, including hematopoietic stem cell transplant
Similarly, to compare the EFS between very high risk (Induction failure) T-LLy
patients treated with HR BFM intensification blocks who have partial or complete response (PR or CR) with those who do not respond (NR).
5. To investigate the prognostic significance of Day 29 BM MRD in T-LLy patients.
6. To determine if protein expression patterns can predict bortezomib response and drug resistance in T-ALL
7. To analyze and target relevant signaling pathways in T-ALL blasts, focusing on Early T cell Precursor ALL
COG AEWS1221: Randomized Phase II Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008, IND# 120449) to Multiagent Chemotherapy for Patients with Newly Diagnosed Metastatic Ewing Sarcoma
1. To compare the event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy with and without the addition of ganitumab (AMG 479).
2. To describe the toxicity of the addition of ganitumab to multimodality therapy for patients with newly diagnosed metastatic Ewing sarcoma.
3. To compare bone marrow response rates and overall survival in patients with newly diagnosed metastatic Ewing sarcoma treated with multiagent chemotherapy with and without the addition of ganitumab.
4. To describe the toxicity of 6 months of ganitumab monotherapy as Maintenance therapy following multimodality therapy in patients with newly diagnosed metastatic Ewing sarcoma.
5. To describe trough levels of ganitumab in a cohort of patients with Ewing sarcoma < 21 years of age treated with 18 mg/kg.
6. To describe the feasibility of and local failure rates following hypofractionated stereotactic body radiotherapy (SBRT) directed at bone metastases in patients with newly diagnosed metastatic Ewing sarcoma.
7. To determine if EFS, overall survival, bone marrow response rates, and toxicity differ based on serum markers of the IGF-1 pathway in patients with newly diagnosed metastatic Ewing sarcoma treated with interval compressed chemotherapy with and without the addition of ganitumab.
8.To determine if EFS, overall survival, and bone marrow response rates differ based on tumor IGF-1R, insulin receptor, and EGFR pathway components in patients with newly diagnosed metastatic Ewing sarcoma treated with interval compressed chemotherapy with and without the addition of ganitumab.
9. To evaluate bone marrow micrometastatic disease and tumor cell surface IGF-1R expression at diagnosis and after 3 and 6 cycles of study therapy in patients with newly diagnosed metastatic Ewing sarcoma.
10.To determine if the presence of germline polymorphisms in EGFR correlate with response to multiagent therapy with and without ganitumab.
11. To investigate the ability of FDG-PET to augment conventional response assessment of primary Ewing sarcoma tumors by MRI.
12.To explore FDG-PET response at the primary tumor as a prognostic marker and as a predictive biomarker of clinical activity of IGF-1R inhibition in patients with newly diagnosed metastatic Ewing sarcoma.
COG AALL1331: Risk-Stratified Randomized Phase III Testing of Blinatumomab (IND# 117467, NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)
1. To compare disease free survival (DFS) of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization).
2. To compare DFS of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization).
3. To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization).
4. To compare OS of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization).
5. To compare the rates of MRD ? 0.01% at the end of Block 2 and Block 3 for HR and IR relapse B-ALL patients in HR/IR randomization.
6. To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD < 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab.
7. To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD ? 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD)
Gemtuzumab Ozogamicin Expanded Access Protocol For Treatment Of Patients In The United States With Relapsed/Refractory Acute Myelogenous Leukemia Who May Benefit From Treatment And Have No Access To Other Comparable/Aletrnative Therapy.
This expanded access protocol is designed in accordance with FDA 21 CFR 312.315
to allow compassionate access to Mylotarg for treatment of our single patient with AML who is thought to have the potential to derive clinical benefit and has exhausted other appropriate and reasonable treatment options. The objective of the protocol is to provide patients compassionate access to Mylotarg.
Therefore, there is no formal primary endpoint. Instead, safety information from
patients receiving Mylotarg in this setting will be carefully monitored, collected and
CHILDREN'S ONCOLOGY GROUP AHOD1331: A Randomized Phase III Study of Brentuximab Vedotin (SGN-35, IND #117117) for Newly Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Adolescents.
1. To assess the event free survival (EFS) of a novel regimen incorporating brentuximab vedotin (Bv; AdcetrisTM) in the chemotherapy backbone of doxorubicin (Adriamycin), vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVEPC) in newly diagnosed high-risk cHL compared to those treated with ABVE-PC.
2. To determine whether children/adolescents with high-risk cHL treated with Bv-AVEPC have a higher rate of early response (determined by FDG-PET) and a reduction in response-directed radiation therapy (RT) compared to those treated with ABVE-PC.
3. To compare the rate of neuropathy (> Grade 3) among patients treated on the Bv-AVEPC (experimental arm) to patients treated on the ABVE-PC (standard arm).
4. To validate and compare the Childhood Hodgkin International Prognostic Score (CHIPS) to conventional Ann Arbor Stage (Stages II B with bulk, III B, IV A or B) in predicting outcome in high-risk childhood cHL.
5. To determine the incidence of preferentially expressed antigen in melanoma (PRAME) and testis-specific antigens in EBV- cHL tumors and the incidence of EBV antigens (EBNA1, LMP1, LMP2) in EBV+ cHL tumors, with the goal of developing strategies to integrate cellular therapy into treatment for newly diagnosed high-risk cHL.
6. To incorporate qualitative visual FDG-PET into response-directed treatment algorithms and explore quantitative FDG-PET and CT definitions of tumor burden and response for incorporation into next generation pediatric cHL risk-stratification schemes.
7. To evaluate the reduction in normal tissue irradiation associated with the current treatment approach compared to the volume of historic IFRT fields.
8. To evaluate EFS and patterns of relapse following protocol-specified RT utilization and treatment volumes.
Patient Reported Outcomes (PRO) of Peripheral Neuropathy and Health-Related Quality of Life
9. To characterize the extent of chemotherapy induced peripheral neuropathy (CIPN), as reported by patients and parent proxies, through serial administration of the FACT-GOG-NTX.
10.To describe the Health-Related Quality of Life (HRQL) consequences of peripheral neuropathy over time by correlating total neuropathy scale scores with the individual items with the CHRIs-Global scale (e.g., physical health, pain, emotional functioning).
11.To perform a cross validation of the FACT-GOG-NTX with the TNS-PV to determine the performance of both measures with the use of brentuximab vedotin in a limited institutional approach in children and adolescents with cHL
12.To assess the resource use and cost implications of Bv in combination with chemotherapy and radiotherapy (RT) for newly diagnosed high-risk cHL in children and adolescents
COG AAML1331: Phase III Study for Patients with Newly Diagnosed Acute Promyelocytic Leukemia (APL) using Arsenic Trioxide and All-Trans Retinoic Acid
1.To eliminate exposure to conventional chemotherapy (including anthracyclines), for patients with standard risk APL, through use of ATO and ATRA based therapy while achieving an event free survival (EFS) that is not inferior compared to historical controls.
2. To significantly reduce exposure to conventional chemotherapy, and in particular, anthracycline exposure, for patients with high risk APL, through use of ATO and ATRA based therapy while achieving an event free survival that is not inferior compared to historical controls.
3. To analyze the clinical impact of FLT3 mutations in pediatric APL.
4. To correlate clinical outcomes with the kinetics of reduction in PML/RARá
transcript level by quantitative RT-PCR (RQ-PCR) in bone marrow and peripheral blood samples from diagnosis to time points during therapy.
5.To monitor incidence of coagulopathy complications, utilizing standardized conventional supportive care, and correlate with a battery of coagulation testing.
6. To evaluate the neurocognitive outcomes of patients treated on this protocol usingpatient-completed, performance-based measures of neuropsychological functioning and parent questionnaire report.
Phase II Study of Denosumab (IND# 127430, NSC# 744010), a RANK Ligand Antibody, for Recurrent or Refractory Osteosarcoma
Goals & Objectives (Scientific Aims)
1. To determine whether denosumab therapy either increases the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to historical COG experience or denosumab therapy produces an objective response rate greater than 5% (Cohort1).
2. To determine whether denosumab therapy increases the disease control rate at 12 months in patients with recurrent resected osteosarcoma as compared to historical COG experience (Cohort2).
1. To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of denosumab in subjects with recurrent osteosarcoma.
2. To describe the tolerability of denosumab in subjects with recurrent osteosarcoma.
3. To report the disease control rate and objective response rate for patients with recurrent osteosarcoma limited to bone.
4. To investigate biological markers potentially associated with response to denosumab in patients with recurrent osteosarcoma.
COG ACCL0933: A Randomized Open Label Trial of Caspofungin versus Fluconazole to Prevent Invasive Fungal Infections in Children Undergoing Chemotherapy for Acute Myeloid Leukemia (AML)
To determine if prophylaxis with caspofungin administered during periods of neutropenia following chemotherapy for acute myeloid leukemia is associated with a lower incidence of proven or probable invasive fungal infections compared with fluconazole.
To determine sensistivity, specificity of biweekly galactomannan and beta-D glucan testing
To test association between single nucleotode polymorphisms in genes involved in innate immunity
Childrens Oncology Group: A Phase III Randomized, Open Label, Multi-center Study on the Safety and Efficacy of
Apixaban for Thromboembolism Prevention versus No Systemic Anticoagulant Prophylaxis
during Induction Chemotherapy in Children with Newly Diagnosed Acute Lymphoblastic
Leukemia (ALL) or Lymphoma (T or B cell) Treated with Pegylated (PEG) L-Asparaginase
1.To compare the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on the composite endpoint of adjudicated non-fatal deep vein thrombosis including symptomatic and asymptomatic deep venous thrombosis, pulmonary embolism (PE), and cerebral venous sinus thrombosis ; and venous thrombus-embolism related-death during 25 - 28 days of open-label treatment in pediatric subjects (1 to < 18 years) with newly
diagnosed ALL or lymphoma (T or B cell), a functioning central venous access device and receiving pegylated L-asparaginase during chemotherapy induction.
2. To assess the effect of prophylactic oral or enteric apixaban versus no administration of systemic prophylactic anticoagulant during induction chemotherapy, on adjudicated major
bleeding events during 25 - 28 days of open-label treatment in pediatric subjects
(1 to < 18 years) with newly diagnosed ALL or lymphoma (T or B cell), a functioning
central venous access device and receiving PEG L-asparaginase during chemotherapy induction.
3. To assess the pharmacokinetics of apixaban in pediatric subjects receiving induction
chemotherapy for ALL or lymphoma (T or B cell), using a population pharmacokinetic
4. To characterize the relationship between apixaban plasma concentration and anti-FXa
activity in pediatric subjects receiving induction chemotherapy for ALL or lymphoma
(T or B cell)
TLC FIT: A Novel Mobile Health Fitness Program for Adolescent and Young Adult (AYA) Childhood Cancer Survivors
The goal of this project is to develop and evaluate the feasibility of TLC FIT (Teens Living with Cancer Fitness Improvement Training), a technology-enhanced fitness program for adolescent and young adult (AYA) survivors of childhood cancers. Advances in treatment have fortunately led to a growth in the number of childhood cancer survivors in the US. Unfortunately, these survivors are at-risk for negative late effects from treatment, including cardiovascular disease and early death. Physical inactivity can exacerbate these risks. Adolescent survivors of childhood cancers in particular have reported significant declines in physical activity that persist following treatment. In preliminary work, we designed an eight-session group-based fitness program for AYA survivors using social cognitive theory. This program incorporated the FitBit, a novel commercially available electronic accelerometer, which allowed for self-monitoring of activity. The FitBit also provided an internet-based website for social networking among participants. The program was feasible and acceptable to participants, and they suggested lengthening the number of sessions to 12. Further, participants reported low levels of engagement with the FitBit website and a strong interest in on-the-go access to program materials outside of weekly group sessions. Therefore, the next step is to significantly enhance the technology by creating a cancer-specific smartphone application (app) that motivates participants to engage in and sustain behavior change. Phase 1 of this project involves the development of the mobile app. Following app development and validation, in Phase 2 we will conduct a randomized pilot trial (n = 88) of TLC FIT to evaluate feasibility and effectiveness.
Childrens Oncology Group APEC14B1: Project:EveryChild A Registry, Eligibility Screening, Biology and Outcome Study
1. To maintain a Childhood Cancer Registry1 for infants, children, adolescents, and young adults with cancer.
2. To utilize clinical and biological data to help determine eligibility or stratification, based on childhood cancer disease classification schemas, for potential enrollment of research subjects onto COG therapeutic clinical trials.
3.To develop a well annotated childhood cancer biorepository for current and future research through the collection of biospecimens (at diagnosis, time of progression, time of recurrence and/or post-mortem), including tumor, host and when feasible parental germline DNA; and key clinical data, including presentation, diagnostic, staging, summary treatment, and outcome information, from every child diagnosed with cancer at COG institutions.
4.To allow use of registry data for permission to be contacted in the future to consider participating in non-therapeutic and prevention research studies involving the child or their parents.