Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Etoposide

Vinorelbine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Ifosfamide

Lenograstim

Etoposide phosphate

Bleomycin

Isophosphamide mustard

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.

Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.

bleomycin sulfate

doxorubicin hydrochloride

liposomal vincristine sulfate

vinorelbine tartrate

cyclophosphamide

etoposide phosphate

prednisone

filgrastim

ifosfamide

Kara Kelly, MD

This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.

SECONDARY OBJECTIVES:

I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.

II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC\* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.

III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.

IV. To describe the patterns of relapse after ABVE-PC\* and risk-adapted radiotherapy.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8, etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7, and filgrastim\* SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.

NOTE: \*Patients do not receive filgrastim on day 8.

Patients undergo clinical restaging and response assessment after 2 courses of induction therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to consolidation therapy. Patients with progressive disease go off study.

CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 consolidation therapy regimens based on response to induction therapy. Patients who develop progressive disease after induction are taken off protocol therapy.

REGIMEN I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

REGIMEN II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

Patients with a continued response after completion of consolidation therapy proceed to risk-adapted radiotherapy.

RISK-ADAPTED RADIOTHERAPY: Beginning at 3 weeks after completion of consolidation chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14 fractions) in the absence of unacceptable toxicity or disease progression. Patients classified as RER receive radiation therapy only to sites of bulky disease. Patients classified as SER receive radiation therapy to sites of bulky disease and areas that remain FDG-PET avid after induction therapy.

After completion of study therapy, patients are followed up periodically for 10 years.

Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma

A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma

Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.

The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.

Survival from enrollment to first event: relapse/progression, second malignancy, or death.

To investigate whether very early response assessment measured by Fluorodeoxyglucose-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.

A description, survival to relapse, of patterns of relapse after Doxorubicin, Bleomycin, Vincristine, Etoposide - Prednisone, Cyclophosphamide (ABVE-PC) and risk-adapted radiotherapy.

The number of patients that experience Common Terminology Criteria (CTC) Version 4 grade 3 or higher non-hematologic toxicity at any time during protocol therapy.

National Cancer Institute (NCI)

Children's Oncology Group

Group 1 includes all patients and the Adverse Event reports of all events across the treatment procedure. Patients who experienced induction only are also included in Group 1. After induction patients were assigned to Group 2 (RER) and Group 3 (SER). While Group 2 and Group 3 are mutually exclusive, they are subsets of Group 1. Hence the Adverse Events in Group 1 will have overlaps with Adverse Events in Group 2 and Group 3.

Group 1

Group 2

Group 3

INDUCTION THERAPY (ABVE-PC)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Australia

Puerto Rico

Region of Enrollment

Results Reporting Coordinator

This analysis excludes n=20 patients who had protocol early terminations or deviations (n=4 Regimen I, n=12 Regimen II, and n=4 Induction only).

Second-event-free Survival

The six patients who received induction and reported death. The analysis here examines whether their death is primarily attributable to treatment or not.

Safety Analysis and Monitoring of Toxic Death

164 Group 1 All Patients received induction therapy.

Event Free Survival

Group 4

Group 5

RER with positive PET-1, Event-Free Survival for RER PET-1 positive patients is compared to that of RER with negative PET-1: n=57 PET-1 positive RER patients, compared to 2 events among n=20 PET-1 negative RER patients. Two PET-1 equivocal RER patients (1 with relapse and 1 censored) are not included in this analysis.

Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative

Group 6

Group 7

161 patients began consolidation therapy: 126 patients received risk-adapted radiotherapy after consolidation therapy ABVE-PC and 35 did not.

Relapse-free Survival

161 patients began consolidation therapy: 81 Group 2 Regimen I and 80 Group 3 Regimen II.

Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy

164 Group 1 All Patients received induction therapy. 161 patients began consolidation therapy: 81 Group 2 Regimen I and 80 Group 3 Regimen II.

Overall Survival

Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

REGIMEN I (RER)

Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

REGIMEN II (SER)

Induction

Consolidation Maintenance

Eye Diseases

Diseases and Abnormalities at or Before Birth

Retinoblastoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Neuroepithelioma

Carboplatin

Includes patients who may or may not require chemotherapy. Patients who require chemotherapy receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity and patients who complete chemotherapy are followed after completion of therapy periodically for at least 5 years. Patients who do not require chemotherapy undergo observation periodically for at least 5 years.

Patients undergo observation periodically for at least 5 years.

carboplatin

etoposide

Murali Chintagumpala, MD

This phase III trial is studying vincristine, carboplatin, and etoposide to see how well they work compared to observation only in treating patients who have undergone surgery for newly diagnosed retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, no additional treatment is needed for the tumor until it progresses. In this case, observation may be sufficient.

OBJECTIVES:

I. Prospectively determine the prevalence of high-risk histopathologic features, such as choroidal involvement, optic nerve invasion, and scleral and anterior segment involvement, in patients with newly diagnosed unilateral retinoblastoma who have undergone enucleation.

II. Demonstrate that patients without certain high-risk features can be successfully treated with enucleation alone by estimating the event-free survival (EFS) (where an event is defined as the occurrence of extraocular or metastatic disease) and overall survival (OS).

III. Estimate the EFS and OS of patients with specific high-risk features who are uniformly treated with adjuvant chemotherapy comprising vincristine, carboplatin, and etoposide.

IV. Estimate the incidence of toxicities associated with the proposed adjuvant chemotherapy regimen.

OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are assigned to 1 of 2 groups according to presence of high-risk histopathologic features.

GROUP 1 (high-risk features): Patients receive vincristine IV and carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

GROUP 2 (no high-risk features): Patients undergo observation periodically for at least 5 years.

GROUP 3 (no consensus regarding high risk features can be reached): Patients undergo Group 1 chemotherapy or observation according to institutional high-risk feature assessment.

After completion of study treatment, patients in group 1 are followed periodically for at least 5 years.

Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma

A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy

EFS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.

OS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone.

Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity.

Proportion of patients who had posterior uveal invasion at enrollment.

Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent.

Proportion of patients that had scleral invasion at enrollment.

Proportion of patients who had anterior chamber seeding at enrollment.

Proportion of patients who had iris infiltration at enrollment.

Proportion of patients who had ciliary body infiltration at enrollment.

Adverse experiences as coded using CTC AE version 4 were collected only for patients who received chemotherapy according to protocol guidelines. Of the 105 eligible patients with high risk features, ninety-three (93) were given protocol chemotherapy based on the assessment of the central pathology review, as described in section 4 of the ARET0332 protocol.

Group 1 (Identified by Central Review as High Risk)

Group 2 (Identified by Central Review as Not High Risk)

Patients receive liposomal vincristine sulfate IV aged based dosage (Pts \< 36 mos: 0.05 mg/kg, Pts \> 36 mos: 1.5 mg/m2, max dose 2 MG) given IV or infusion on day 1, carboplatin aged based dosage (Pts \< 36 mos: 18.6 mg/kg Pts \> 36 mos: 560 mg/m2) IV on day 1, and Etoposide aged based dosage (Pts \< 36 mos: 5 mg/kg, Pts \> 36 mos: 150 mg/m2) IV on days 1 and 2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

liposomal vincristine sulfate: Given IV

carboplatin: Given IV

etoposide: Given IV

Group 1 (High Risk)

Group 2 (Not High Risk)

Total

New Zealand

India

Mexico

Bangladesh

The COG SDC reviewed the NLM notification related to ct.gov AE/SAE reporting. The information in 'Additional Description' is accurate with respect to data supplied to ct.gov.COG plans to submit data AE/SAE data consistent with the text in this field.

Only eligible patients are considered in the characterization of EFS at 2 years.

Event-free Survival (EFS)

Only eligible patients are considered for this outcome measure. This is calculated as the total number of patients enrolled in each group with the number ineligible in each group subtracted as reported on the participant flow template.

Overall Survival (OS)

Adverse experiences as coded using CTC AE version 4 were collected only for patients who received chemotherapy according to protocol guidelines. Of the 105 eligible patients with high risk features, ninety-three (93) were given protocol chemotherapy based on the assessment of the central pathology review, as described in section 4 of the ARET0332.

Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

This outcome measure is calculated by combining all groups as defined in the trials record.

All Patients

Central review of the biological materials for this aim was available on only 313 patients. This outcome measure is calculated by combing all groups as characterized in the Patient Flow.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma	NCT01026220	Childhood Nodul... Stage III Child... Stage IV Childh...	bleomycin sulfa... doxorubicin hyd... liposomal vincr... vinorelbine tar... cyclophosphamid... etoposide phosp... prednisone filgrastim ifosfamide	- 21 Years	Children's Oncology Group
Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma	NCT00335738	Intraocular Ret...	liposomal vincr... carboplatin etoposide	- 6 Years	Children's Oncology Group
Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma	NCT01026220	Childhood Nodul... Stage III Child... Stage IV Childh...	bleomycin sulfa... doxorubicin hyd... liposomal vincr... vinorelbine tar... cyclophosphamid... etoposide phosp... prednisone filgrastim ifosfamide	- 21 Years	Children's Oncology Group
Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma	NCT00335738	Intraocular Ret...	liposomal vincr... carboplatin etoposide	- 6 Years	Children's Oncology Group
Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma	NCT00335738	Intraocular Ret...	liposomal vincr... carboplatin etoposide	- 6 Years	Children's Oncology Group

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