Symptoms and General Pathology

All Conditions

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Eye Diseases

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Lymphoma

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Glioma

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Neoplasms by Histologic Type

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Lymphatic Diseases

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Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Retinal Neoplasms

Eye Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

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Germ Cells Tumors

Neuroepithelioma

Childhood Brain Stem Glioma

Supratentorial Primitive Neuroectodermal Tumor

Medulloblastoma, Childhood

Cerebellar Astrocytoma, Childhood

Cerebral Astrocytoma, Childhood

Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified

Patients with solid tumors are stratified according to tumor histology (neuroblastoma vs Ewing's sarcoma \[closed to accrual as of 5/19/03\]/peripheral primative neuroectodermal tumor \[PNET\] vs osteosarcoma \[closed to accrual as of 5/19/03\] vs rhabdomyosarcoma vs non-Hodgkin's lymphoma vs other solid tumors). Patients with CNS tumors are stratified according to tumor histology (medulloblastoma/PNET vs ependymoma vs brainstem glioma vs other CNS tumors).

Patients receive rebeccamycin analogue IV over 1 hour on day 1. Treatment continues every 21 days for a total of 16 courses in the absence of disease progression or unacceptable toxicity.

becatecarin

Anne-Marie Langevin, MD

Phase II trial to study the effectiveness of rebeccamycin analogue in treating children who have solid tumors or non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

OBJECTIVES:

I. Determine the response in children with solid tumors or non-Hodgkin's lymphoma treated with rebeccamycin analogue.

II. Determine and maintain a plasma concentration of at least 5 µg/mL of this drug in these patients.

III. Determine the toxicity of this drug in these patients. IV. Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients with solid tumors are stratified according to tumor histology (neuroblastoma vs Ewing's sarcoma \[closed to accrual as of 5/19/03\]/peripheral primative neuroectodermal tumor \[PNET\] vs osteosarcoma \[closed to accrual as of 5/19/03\] vs rhabdomyosarcoma vs non-Hodgkin's lymphoma vs other solid tumors). Patients with CNS tumors are stratified according to tumor histology (medulloblastoma/PNET vs ependymoma vs brainstem glioma vs other CNS tumors).

Patients receive rebeccamycin analogue IV over 1 hour on day 1. Treatment continues every 21 days for a total of 16 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 2 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Rebeccamycin Analogue in Treating Children With Solid Tumors or Non-Hodgkin's Lymphoma

A Phase II Trial of Rebeccamycin Analogue (NSC #655649) in Children With Solid Tumors

National Cancer Institute (NCI)

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Carboplatin

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Topotecan

Lenograstim

Etoposide phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Topoisomerase I Inhibitors

filgrastim

carboplatin

cyclophosphamide

doxorubicin hydrochloride

etoposide

topotecan hydrochloride

autologous bone marrow transplantation

radiation therapy

Carlos Rodriguez-Galindo, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus radiation therapy followed by bone marrow transplantation in treating patients who have retinoblastoma.

OBJECTIVES:

* Evaluate the feasibility of sequential therapy with carboplatin, etoposide, cyclophosphamide, doxorubicin, topotecan and radiotherapy followed by autologous bone marrow transplantation in patients with extrachoroidal or metastatic retinoblastoma.
* Assess this treatment regimen in terms of response and toxicity before and after autologous bone marrow transplantation in this patient population.

OUTLINE: Patients receive carboplatin IV on day 1 and etoposide IV over 1 hour daily on days 1-3 of weeks 0, 6, and 12, plus cyclophosphamide IV or orally daily on days 1-7, doxorubicin IV on day 8 and carboplatin IV over 1 hour on day 10 on weeks 3, 9, and 15. Beginning on week 6, patients receive concurrent radiotherapy 5 days a week over 4-6 weeks. Patients with meningeal involvement receive topotecan intrathecally twice weekly for 3 weeks and then weekly for 3 weeks before starting radiotherapy. Beginning one day after each treatment course, patients receive filgrastim (G-CSF) subcutaneously daily for 10 days.

Patients undergo bone marrow collection before or after week 6. Following hematologic recovery, patients receive several days of high dose chemotherapy consisting of cyclophosphamide and topotecan followed by bone marrow reinfusion.

Patients are followed at 6, 9, and 12 months, and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Combination Chemotherapy, Radiation Therapy, and Bone Marrow Transplantation in Treating Patients With Retinoblastoma

Treatment for Extrachoroidal or Metastatic Retinoblastoma

St. Jude Children's Research Hospital

Dermatologic Agents

Vincristine

Cisplatin

Podophyllotoxin

Thiotepa

Adjuvants, Immunologic

Tubulin Modulators

Antimitotic Agents

Keratolytic Agents

INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF SC beginning on day 3 and continuing until blood counts recover.

CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV.

AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0 and receive G-CSF SC beginning on day 1 and continuing until blood counts recover.

RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.

Undergo peripheral blood stem cell or bone marrow transplant

Autologous Bone Marrow Transplantation

Autologous Hematopoietic Stem Cell Transplantation

Filgrastim

In Vitro-Treated Peripheral Blood Stem Cell Transplantation

Radiation Therapy

Vincristine Sulfate

Ira J Dunkel

This phase III trial is studying the side effects and how well giving combination chemotherapy together with autologous stem cell transplant and/or radiation therapy works in treating young patients with extraocular retinoblastoma. Giving chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and/or bone marrow and stored. More chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Radiation therapy uses high energy x-rays to kill tumor cells. Giving radiation therapy after combination chemotherapy and/or autologous stem cell transplant may kill any remaining tumor cells.

OBJECTIVES:

I. To estimate the proportion of 3 groups of patients with extraocular retinoblastoma (stage 2 and 3: regional extra-ocular disease;, stage 4a: disseminated metastatic disease not involving the central nervous system \[CNS\]; or stage 4b: patients with CNS disease) who achieve long-term event-free survival after treatment with aggressive multimodality therapy compared to historical controls.

II. To estimate the response rate to the induction phase of the regimen. III. To evaluate the toxicities associated with this regimen.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive vincristine intravenously (IV) on days 0, 7, and 14, cisplatin IV over 6 hours on day 0, cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1 and 2, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 and continuing until blood counts recover.

Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of induction chemotherapy, patients with stage 2 or 3 disease who have at least a partial response proceed to radiotherapy. Patients with stage 4a or 4b disease who have at least a partial response proceed to high-dose consolidation chemotherapy and autologous stem cell infusion.

STEM CELL HARVESTING (stage 4a or 4b disease only): Peripheral blood stem cells (preferred) or bone marrow cells are collected after at least 1 course of induction chemotherapy.

HIGH-DOSE CONSOLIDATION CHEMOTHERAPY (stage 4a or 4b disease only): Patients receive carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3.

AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0. Patients then receive filgrastim subcutaneously (SC) beginning on day 1 and continuing until blood counts recover.

RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion. Patients with stage 4a disease who achieve a complete response to induction chemotherapy or with less than 5 mm of residual tumor at the time of planned irradiation, or patients with stage 4b disease who achieve a complete response to induction chemotherapy do not undergo radiotherapy.

After completion of study therapy, patients are followed every 3 months for 1 year and then annually thereafter for 9 years.

Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma

A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma

The probability of surviving patients who did not experience events at 1 year following enrollment. An event is defined as relapse, second malignancy, or death from any cause.

This study used a modified version of the international criteria for neuroblastoma response. The response rate to the induction phase of the regimen and a corresponding 95% confidence interval will be calculated for all strata combined.

Grade 3 and higher toxicities will be descriptively summarized.

Children's Oncology Group

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.

Patients with orbital disease (including microscopic trans-scleral invasion seen on enucleation pathology), optic nerve margin (+), and/or regional nodal disease, but no other sites of metastases. Stage 2 and 3 patients will receive Induction chemotherapy and External Beam Radiation Therapy, but will not receive Consolidation therapy (High-Dose Chemotherapy with Stem Cell Rescue).

Stage 2/3 Patients

Patients with overt distant metastatic disease (such as bone, bone marrow, and/or liver) but no detectable CNS involvement. Patients will receive Induction chemotherapy, Stem Cell Harvesting, Consolidation with Stem Cell Rescue, and depending on response to Induction chemotherapy, possibly External Beam Radiation Therapy.

Stage 4a Patients

Patients with overt CNS involvement (brain parenchyma, leptomeninges and CSF cytology). Patients with trilateral retinoblastoma will be included. Patients will receive Induction chemotherapy, Stem Cell Harvesting, Consolidation with Stem Cell Rescue, and depending on response to Induction chemotherapy, possibly External Beam Radiation Therapy.

Stage 4b Patients

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Canada

Argentina

Egypt

Brazil

Chile

Region of Enrollment

Results Reporting Coordinator

Ineligible patients were excluded from analysis

Event-free Survival (EFS)

All eligible Stage 2/3, Stage 4a, and Stage 4b patients

All Eligible Patients

Response Rate to the Induction Phase of the Regimen

Abdominal pain

Acute kidney injury

Alanine aminotransferase increased

Anemia

Anorexia

Apnea

Aspartate aminotransferase increased

Catheter related infection

Dehydration

Depressed level of consciousness

Diarrhea

Encephalopathy

Enterocolitis

Enterocolitis infectious

Esophagitis

Febrile neutropenia

Fever

GGT increased

Gastric hemorrhage

Hearing impaired

Hypermagnesemia

Hypertension

Hypoalbuminemia

Hypocalcemia

Hypoglycemia

Hypokalemia

Hypomagnesemia

Hyponatremia

Hypophosphatemia

Hypotension

Hypoxia

Infections and infestations - Other, specify

Lower gastrointestinal hemorrhage

Lung infection

Lymphocyte count decreased

Mucositis oral

Nausea

Nervous system disorders - Other, specify

Neutrophil count decreased

Oral pain

Pain

Peripheral motor neuropathy

Pharyngeal mucositis

Platelet count decreased

Pneumonitis

Rectal pain

Seizure

Sepsis

Sinus tachycardia

Sinusitis

Skin infection

Upper respiratory infection

Three ineligible patients were excluded from this analysis. Two patients who did not receive therapy were also excluded from this analysis.

Percentage of Participants With Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rebeccamycin Analogue in Treating Children With Solid Tumors or Non-Hodgkin's Lymphoma	NCT00006102	Brain and Centr... Lymphoma Neuroblastoma Retinoblastoma Sarcoma Unspecified Chi...	becatecarin	- 21 Years	National Cancer Institute (NCI)
Combination Chemotherapy, Radiation Therapy, and Bone Marrow Transplantation in Treating Patients With Retinoblastoma	NCT00004006	Retinoblastoma	filgrastim carboplatin cyclophosphamid... doxorubicin hyd... etoposide topotecan hydro... autologous bone... radiation thera...	- 15 Years	St. Jude Children's Research Hospital
Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma	NCT00554788	Extraocular Ret...	Autologous Bone... Autologous Hema... Carboplatin Cisplatin Cyclophosphamid... Etoposide Filgrastim In Vitro-Treate... Radiation Thera... Thiotepa Vincristine Sul...	- 10 Years	Children's Oncology Group
Genetic Mutations and Environmental Exposure in Young Patients With Retinoblastoma and in Their Parents and Young Healthy Unrelated Volunteers	NCT00690469	Extraocular Ret... Intraocular Ret... Recurrent Retin...	Laboratory Biom... Questionnaire A...	-	Children's Oncology Group
Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor	NCT00003273	Brain and Centr... Neuroblastoma Retinoblastoma Sarcoma	filgrastim carboplatin cisplatin cyclophosphamid... etoposide leucovorin calc... methotrexate temozolomide thiotepa vincristine sul... autologous bone... peripheral bloo... radiation thera...	- 10 Years	NYU Langone Health
Combination Chemotherapy, Radiation Therapy, and Bone Marrow Transplantation in Treating Patients With Retinoblastoma	NCT00004006	Retinoblastoma	filgrastim carboplatin cyclophosphamid... doxorubicin hyd... etoposide topotecan hydro... autologous bone... radiation thera...	- 15 Years	St. Jude Children's Research Hospital
Genetic Mutations and Environmental Exposure in Young Patients With Retinoblastoma and in Their Parents and Young Healthy Unrelated Volunteers	NCT00690469	Extraocular Ret... Intraocular Ret... Recurrent Retin...	Laboratory Biom... Questionnaire A...	-	Children's Oncology Group

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