Neoplasms

Nervous System Diseases

All Conditions

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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Rare Diseases

Brain Neoplasms

Neuroblastoma

Sarcoma

Lymphoma

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Sarcoma, Ewing

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Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Connective and Soft Tissue

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Myosarcoma

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Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

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Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

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Male Urogenital Diseases

Genetic Diseases, Inborn

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Soft Tissue Sarcoma

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Germ Cells Tumors

Wilms' Tumor

Ewing Sarcoma

Neuroepithelioma

Medulloblastoma, Childhood

All Drugs and Chemicals

Antineoplastic Agents

Herbal and Botanical

Estrogens

Genistein

Protective Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Phytoestrogens

Hormones

Hormone Antagonists

Soy Bean

Genistein daily throughout chemotherapy cycles 1 and 2, and placebo daily during chemotherapy cycles 3 and 4

Placebo daily throughout chemotherapy cycles 1 and 2, and genistein daily during chemotherapy cycles 3 and 4

Estrogen-like compound (isoflavone) derived from soybeans

Placebo

William C. Petersen, Jr., M.D.

Toxicities related to pediatric cancer treatment can lead to significant illness, organ damage, treatment delays, increased health care cost, and decrease in quality of life. Such toxicities are largely due to tissue damage sustained by chemotherapy, and strategies designed to limit such cellular damage to normal tissues may reduce therapy-related morbidity and mortality. In addition to their in vitro and in vivo anti-cancer effects, naturally occurring soy isoflavones have anti-inflammatory and anti-oxidant properties, and have been shown to reduce side effects of therapy in adult oncology clinical trials. This study will examine the effect of genistein, the major isoflavone component in soybeans and the most extensively studied of the soy isoflavones, on short-term side effects of myelosuppressive chemotherapy in pediatric cancer patients. Subjects will be randomized to receive either: a) 30 mg genistein daily throughout chemotherapy Cycles 1 and 2 and placebo during chemotherapy Cycles 3 and 4; or b) placebo daily during chemotherapy Cycles 1 and 2 and 30 mg genistein daily during chemotherapy Cycles 3 and 4. Investigators hypothesize that subjects will have fewer short-term therapy-related side effects during cycles of chemotherapy given in conjunction with genistein supplementation than cycles given with placebo.

This is a multi-center, randomized, double blind, placebo-controlled crossover study to evaluate the effect of soy isoflavones on the short term untoward effects of myelosuppressive chemotherapy used to treat pediatric cancers. Newly diagnosed cancer patients aged 1-21 years will be registered to the study and informed consent will be obtained prior to any study-related procedures. Stratification will be based on length of chemotherapy cycles, between 14 day and 21 day cycles. Within strata registered subjects will be randomized 1:1 to one of two schedules:

Arm A: Subjects will receive genistein daily throughout chemotherapy cycles 1 and 2, and placebo during chemotherapy cycles 3 and 4

Arm B: Subjects will receive placebo daily throughout chemotherapy cycles 1 and 2, and genistein during chemotherapy cycles 3 and 4

Subjects will be assessed for safety and efficacy during each cycle with clinical labs, cytokine panels, and physical exams. Drug compliance will be monitored by use of a patient diary as well as monitoring of serum genistein levels. Adverse events will be monitored starting on Cycle 1 Day 1 through 30 days following the last day of protocol therapy (genistein/placebo).

Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)

A Randomized, Placebo-Controlled Pilot Study of Genistein Supplementation in Pediatric Cancer Patients Receiving Myelosuppressive Chemotherapy

This includes hearing loss/tinnitus, motor neuropathy, oral mucositis

University of Virginia

Director, Pediatric Novel Therapeutics Program (Hematology/Oncology)

Genistein daily throughout chemotherapy cycles 1 and 2, and placebo daily during chemotherapy cycles 3 and 4

Genistein: Estrogen-like compound (isoflavone) derived from soybeans

Placebo: Pill that contains no medicine

Arm A: Genistein Followed by Placebo - GENISTEIN Cycles

Placebo daily throughout chemotherapy cycles 1 and 2, and genistein daily during chemotherapy cycles 3 and 4

Genistein: Estrogen-like compound (isoflavone) derived from soybeans

Placebo: Pill that contains no medicine

Arm B: Placebo Followed by Genistein - GENISTEIN Cycles

Arm A: Genistein Followed by Placebo - PLACEBO Cycles

Arm B: Placebo Followed by Genistein - PLACEBO Cycles

Arm A: Genistein Followed by Placebo

Arm B: Placebo Followed by Genistein

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

William Petersen

Genistein cycles

Placebo cycles

Time to Neutrophil Count Recovery Following Myelosuppressive Chemotherapy

ESR, Genistein cycles

ESR, Placebo cycles

Serum Marker Levels of Inflammation Erythrocyte Sedimentation Rate (ESR; mm/hr) During Cycles of Chemotherapy

Genistein Cycles

Placebo Cycles

Number of Days That Participants Experience Adverse Events That Are Commonly Caused by Chemotherapy Treatment

Number of Participants Who Experience Adverse Events That Are Commonly Caused by Chemotherapy Treatment

Severity of Adverse Events That Are Commonly Caused by Chemotherapy Treatment Based on CTCAE Severity Criteria

Number of Days That Participants Are Hospitalized or Have Prolonged Hospitalization Due to an Adverse Event

Number of Days That Planned Cancer Treatment is Delayed Due to an Adverse Event

Percentage of Participants Requiring Reduced Treatment Doses Due to an Adverse Event

Number of Days That Antimicrobial Treatment is Administered

Number of Cycles Where Granulocyte-colony Stimulating Factor (G-CSF) is Administered

Number of Times That a Blood Product is Administered for Anemia, Decreased Platelets, Abnormal Bleeding, or the Subject's Best Interest

CRP, Genistein cycles

CRP, Placebo cycles

Serum Marker Levels of Inflammation C-reactive Protein (CRP; mg/dL) During Cycles of Chemotherapy

Overall Study

Leukemia

Hematologic Neoplasms

Hematologic Diseases

Acute Graft Versus Host Disease

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Etoposide

Bendamustine Hydrochloride

Dexamethasone acetate

BB 1101

Etoposide phosphate

Clofarabine

Glucocorticoids

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

All participants who meet eligibility for this study will follow the same treatment regimen.

INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone.

Route of administration: intravenously (IV) over approximately 60 minutes, days 1-5.

Bendamustine

Route of administration: Used in substitution for etoposide in participants who experience allergic reaction, Etopophos® will be administered IV.

Route of administration: three times daily orally (by mouth), days 1-5.

Sima Jeha, MD

Participants with relapsed or refractory leukemia or lymphoma will be recruited for this study to find whether or not the addition of a new drug called bendamustine will be safe and possible to give with other chemotherapy drugs. This drug is approved by the Food and Drug Administration (FDA) for the treatment of other cancers in adults that are similar to those being studied in the research trial.

PRIMARY OBJECTIVES

* To establish the maximum tolerated dose (MTD) of bendamustine in combination with clofarabine and etoposide in pediatric participants with hematologic malignancies.
* To characterize the safety profile and dose-limiting toxicities (DLTs) of bendamustine in combination with clofarabine and etoposide.

SECONDARY OBJECTIVES

* To estimate event-free survival at 4 months.
* To estimate minimal residual disease (MRD) levels present at end of each cycle of therapy in participants with leukemia.
* To characterize the pharmacokinetic profile of bendamustine in the proposed regimen.

Bendamustine will be combined with clofarabine and etoposide in a five-day cycle. Dexamethasone will be given to prevent capillary leak syndrome associated with clofarabine.

If the participant does not develop progressive disease or a dose-limiting toxicity (DLT) during the first cycle, a second cycle may be administered as a bridge to transplant. Each cycle lasts 21-28 days (or until count recovery).

Concomitant intrathecal therapy can be given at the investigator's discretion, but not on the same days as chemotherapy. Recommendations are triple intrathecal therapy (methotrexate, hydrocortisone, cytarabine) weekly for participants with CNS2 or CNS3 disease, and every two weeks for participants with CNS1 disease. Leucovorin may be given according to institutional guidelines.

The intent of this study design is for all participants to receive and complete one course of therapy. Participants who exhibit signs of disease progression or experience an unacceptable toxicity will be discontinued from protocol treatment.

Bendamustine Hydrochloride, Clofarabine, and Etoposide in Treating Younger Patients With Relapsed or Refractory Hematologic Malignancies

A Phase I Trial of Bendamustine in Combination With Clofarabine and Etoposide in Pediatric Patients With Relapsed or Refractory Hematologic Malignancies

Establish MTD of bendamustine in combination with clofarabine and etoposide.

Characterize safety profile and DLTs of bendamustine in combination with clofarabine and etoposide

Event-free survival (EFS) time will be calculated from on therapy to any kind of failure or to last contact date for participants who are alive without any failure at the last contact date. The time to EFS will be set to 0 for participants who fail to achieve complete remission. Kaplan-Meier estimates of EFS curves will be computed, along with estimates of standard errors by the method of Peto. Four month EFS, as well as longer term survival rates (6 month and 1 year) will be estimated with 95% confidence intervals.

The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.

Plasma concentrations of bendamustine will be measured using an established LC-MS/MS assay. Bendamustine pharmacokinetic parameters such as Cmax, tmax, AUC (0-t), t1/2, and clearance will be estimated using population-based modeling techniques.

Teva Pharmaceuticals USA

St. Jude Children's Research Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)	NCT02624388	Lymphoma Childhood Lymph... Solid Tumor Childhood Solid... Neuroblastoma Ewing Sarcoma Hodgkin Lymphom... Non-Hodgkin Lym... Rhabdomyosarcom... Soft Tissue Sar... Medulloblastoma Germ Cell Tumor Wilms Tumor Brain Neoplasms Medulloblastoma... Neuroectodermal...	Genistein Placebo	1 Year - 21 Years	University of Virginia
Bendamustine Hydrochloride, Clofarabine, and Etoposide in Treating Younger Patients With Relapsed or Refractory Hematologic Malignancies	NCT01900509	Hodgkin Lymphom... Non-Hodgkin Lym... Acute Leukemia	Bendamustine Clofarabine Etoposide Etoposide phosp... Dexamethasone	- 21 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for childhood lymphoma