|Protocol||Trial Name and Objective|
A Phase II, Randomized, Three-Arm Study of Abiraterone Acetate Alone, Abiraterone Acetate Plus Degarelix, a GnRH Antagonist, and Degarelix Alone for Patients with Prostate Cancer with a Rising PSA and Nodal Disease Following Definitive Radical Prostatectomy
The primary endpoint for each cohort is progression-free survival (PFS) at 18 months from the start of randomization (PSA0). PFS is defined as an undetectable (less than or equal to 0.05 ng/mL) PSA with a non-castrate level of testosterone (greater than 150 ng/dL). Pathological lymph nodes (whether target or non-target) must also have reduction in short axis to less than 10mm (Compelte Response per RECIST) in order to meet the criteria for PFS.
Secondary endpoints: (1) PSA response rate (Percentage of patients with an undetectable PSA at 8 months from PSA0). (2) Effects of each arm on overall quality of life, with particular attention to libido, potency, anxiety, depression, hot flashes and fatigue. (3) Frequency and intensity of non-hematologic adverse events. (4) Testosterone and leuteinizing hormone (LH) recovery rates.
Tertiary endpoint: Correlative tissue analysis with clinical outcomes while on study treatment.
A Pilot Study of Romidepsin for Therapy of Graft-versus-Host Disease
1.1 Primary Objective:
To determine if romidepsin should be developed as a therapy for patients with steroid-refractory GVHD.
1.2 Primary Hypothesis:
The hypothesis is that romidespin will reduce GVHD in some patients with steroid refractory disease. If greater than or equal to 2/10 patients with either aGVHD or cGVHD demonstrate a PR, a formal phase 2 study will be developed.
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.
Integrated Risk Stratification and Transplant Decision Making for Patients with Acute Myelogenous Leukemia
1.1 Primary Objective(s)
1. To determine the effect genomic mutations have on treatment recommendations and medical decision making with respect to allogeneic stem cell transplantation in CR1 in patients with intermediate risk AML.
2. To integrate novel mutation analysis, CD25 expression, minimal residual disease (MRD) analysis and clinical factors into an allogeneic transplantation medical-decision making model that refines risk assessment by using commercially available detailed genetic analysis.
1.2 Secondary Objective(s)
1. To determine the outcomes of these patients with intermediate risk disease and defining outcomes in these patients who do and do not undergo stem cell transplantation in CR1.
1.3 Additional Objective(s)
1. To obtain genomic data for data storage and future computational analysis and correlation with clinical data;
2. To perform a Health Economic Analysis of the impact of the genomic mutations on transplant decision making and estimates of patient outcomes;
3. To determine the relative sensitivity and cost of genomic mutations and standard FISH assays in detecting common AML-associated gene fusions.
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.
A Phase 1, Open-label, Adaptive Dose-escalation, Multicenter Study to Evaluate the
Tolerability, Safety, Pharmacokinetics, and Anti-tumor Activity of ADCT-402
in Patients with Relapsed or Refractory B-lineage Acute Lymphoblastic
* Evaluate the safety and tolerability and determine the maximum tolerated dose (MTD) of ADCT-402 in patients with relapsed or refractory B-ALL in Part 1.
* Determine the recommended dose of ADCT-402 for Part 2 (expansion).
* Evaluate the safety and tolerability of ADCT-402 in Part 2 (expansion) at the dose level recommended in Part 1.
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.
CC-122-ST-001: A Phase IA/IB, Multi-center,Open-Label, Dose Finding Study To Assess The Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Pleiotrophic Pathway modifier CC-122 administered orally to subjects with advanced solid tumors, NHL and Multiple Myeloma.
1. To determine the safety and tolerability of CC-122 given orally and to define the non-tolerable dose, MDT and the recommended phase 2 dose.
2. To determine the PK and extent of urinary excretion of CC-122.
1. Preliminary assessment of the anti-tumor activity of CC-122.
2. To determine the CNS penetration of CC-122.
3. To evaluate the PD effects of CC-122 on gene expression, cytoskeletal structure and cell surface organization in peripheral blood cell components.
4. To evaluate modulation of circulating cytokines in the plasma.
5. To evaluate modulation of immune effector cells and their subtypes in peripheral blood.
6. To evaluate the modulation of cytokine production in ex vivo LPS and anti-CD3 stimulated peripheral blood.
7. To determine the plasmacogenomic relationship between tumor gene sequence or copy number and response.
8. To explore the relationship between PK and PD effects of CC-122.
9. To explore the effect of CC-122 on biomarkers of angiogenesis in pre-and during treatment tumor biopsies when available.
10. To characterize the principle metabolites of CC-122 in plasma and urine.
11.To determine the PK of CC-122 anantiomers in urine and plasma.
12. To assess relationship between renal function and the PK of CC-122.
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 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
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
R1979-HM-1333: An Open-label, Multi-center Phase I Study to Investigate the Safety and Tolerability of REGN1979, an anti-CD20 x anti-CD3 bispecific monoclonal antibody, in Patients with CD20+ B-cell Malignancies previously treated with CD20 directed antibody therapy.
The primary objective of the study is to assess the safety, tolerability, and dose-limiting toxicities (DLTs) of REGN1979 administered intravenously (IV).
The secondary objectives of the study are:
* To characterize the pharmacokinetic (PK) profile of REGN1979
* To assess the immunogenicity of REGN1979
* To study the preliminary antitumor activity of REGN1979 administered to patients with CD20+ B-cell malignancies (non-Hodgkin's lymphoma [NHL] and chronic lymphocytic leukemia [CLL]) previously treated with anti-CD20 antibody therapy.
o Minimal residual disease (MRD) assessments in patients with CLL
The exploratory objectives of the study are:
* To evaluate biomarkers that may correlate with mechanism of action, observed toxicity, and potential anti-tumor activity including, but not limited, to:
o Cytokine profiling
o Peripheral blood B-cell and T-cell subsets and immune phenotyping
o Changes in gene expression in peripheral blood
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
ECOG 4512: A Phase III Double-Blind Trial for Surgically Resected Early Stage Non-Small Cell Lung Cancer: Crizotinib versus Placebo for Patients with Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein.
To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) over placebo for patients with stage IB ? 4cm, II and IIIA, ALK-positive NSCLC following surgical resection.
1. To evaluate and compare disease-free survival (DFS) associated with crizotinib and placebo
2. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting
3. To collect tumor tissue and blood specimens for future research.
An Open Label, Phase 2 Study to Evaluate Efficacy and Safety of Daratumumab in Relapsed or Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma
The study will evaluate daratumumab separately in three relapsed or refractory NHL subtypes that are CD38 positive: mantle cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL), and follicular lymphoma (FL). There are two main objectives:
h To assess overall response rate (ORR, including complete response (CR) and partial response (PR)),of daratumumab in subjects with CD38+ disease in each NHL subtype.
h To evaluate association between ORR and CD38 expression level in order to determine a threshold for CD38 expression level in each NHL subtype, above which daratumumab activity is enhanced.
For each subtype of NHL, the secondary objectives are:
h To assess the duration of response (DoR), progression-free survival (PFS), and overall survival (OS)
h To assess time to response
h To assess and correlate the CD38 expression level with DoR, PFS and OS
h To assess pharmacokinetics of daratumumab
h To assess immunogenicity of daratumumab
h To assess the safety profile of daratumumab
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)