DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Therapy for Children With Advanced Stage Neuroblastoma

Information source: St. Jude Children's Research Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Neuroblastoma

Intervention: cyclophosphamide (Drug); topotecan (Drug); hu14.18K322A (Biological); peripheral blood stem cell harvest (Procedure); surgical resection (Procedure); cisplatin (Drug); etoposide (Drug); doxorubicin (Drug); vincristine (Drug); busulfan (Drug); melphalan (Drug); peripheral blood stem cell transplantation (Biological); natural killer cell infusion (Biological); radiation therapy (Radiation); GM-CSF (Biological); G-CSF (Biological); mesna (Drug); levetiracetam (Drug); interleukin-2 (Biological); Isotretinoin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: St. Jude Children's Research Hospital

Official(s) and/or principal investigator(s):
Wayne L. Furman, MD, Principal Investigator, Affiliation: St. Jude Children's Research Hospital

Overall contact:
Wayne L. Furman, MD, Phone: 866-278-5833, Email: info@stjude.org

Summary

Neuroblastoma is the most common extracranial solid tumor in childhood, with nearly 50% of patients presenting with widespread metastatic disease. The current treatment for this group of high-risk patients includes intensive multi-agent chemotherapy (induction) followed by myeloablative therapy with stem-cell rescue (consolidation) and then treatment of minimal residual disease (MRD) with isotretinoin. Recently a new standard of care was established by enhancing the treatment of MRD with the addition of a monoclonal antibody (ch14. 18) which targets a tumor-associated antigen, the disialoganglioside GD2, which is uniformly expressed by neuroblasts. Despite improvement in 2-year event-free survival (EFS) of 20%, more than one-third of children with high-risk neuroblastoma (HR defined in) still cannot be cured by this approach. Therefore, novel therapeutic approaches are needed for this subset of patients. This study will be a pilot Phase II study of a unique anti-disialoganglioside (anti-GD2) monoclonal antibody (mAb) called hu14. 18K322A, given with induction chemotherapy. PRIMARY OBJECTIVE:

- To study the efficacy [response: complete remission + partial remission (CR+PR)] to two

initial courses of cyclophosphamide and topotecan combined with hu14. 18K322A (4 doses/course followed by GM-CSF) in previously untreated children with high-risk neuroblastoma. SECONDARY OBJECTIVES:

- To study the feasibility of delivering hu14. 18K322A to 6 cycles induction chemotherapy

and describe the antitumor activity (CR+PR) of this 6 course induction therapy.

- To estimate local control and pattern of failure associated with intensity modulated

radiation therapy dose delivery in high-risk abdominal neuroblastoma.

- To describe the tolerability of four doses of hu14. 18K322A with allogeneic natural

killer (NK) cells from an acceptable parent, in the immediate post-transplant period

[day +2 - +5 after peripheral blood stem cell (PBSC) infusion] in consenting

participants.

- To describe the tolerability of hu14. 18K322A with interleukin-2 and GM-CSF as treatment

for minimal residual disease (MRD).

Clinical Details

Official title: Neuroblastoma Protocol 2012: Therapy for Children With Advanced Stage High-Risk Neuroblastoma

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Number of participants with complete or partial response

Secondary outcome:

Failure rate for the 6 cycles of induction therapy.

Local failure rate

Dose limiting toxicity (DLT) or severe (grade 3 or 4) VoD

Dose limiting toxicity (DLT)

Detailed description: The phases of the study are: 1. Screening phase: Tests and evaluations will be done before treatment starts. 2. Induction phase: Includes chemotherapy plus hu14. 18K322A mAb. Participants will also have surgery during this part of the study to remove as much tumor as possible. 3. Consolidation/Intensification phase: Includes high doses of chemotherapy and blood stem cell transplantation with additional, experimental "minimal residual disease" (MRD) treatment.. Participants will also get radiation treatment to all sites of the tumor(s) after recovery from the stem cell transplant. 5. Maintenance/MRD treatment phase: With immune therapy in addition to the standard treatment with the drug isotretinoin. 4. Maintenance/MRD treatment phase: With immune therapy in addition to the standard treatment with the drug isotretinoin.

Eligibility

Minimum age: N/A. Maximum age: 18 Years. Gender(s): Both.

Criteria:

PARTICIPANT Inclusion Criteria:

- Participants <19 years of age (eligible until 19th birthday).

- Newly diagnosed, advanced stage, high-risk neuroblastoma defined as one of the

following:

- Children < 1 year with International Neuroblastoma Staging System (INSS) stage

2a, 2b, 3, 4 or 4S disease AND MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal).

- INSS 2a or 2b disease AND MYCN amplification, regardless of age or additional

biologic features

- INSS stage 3 AND:

1. MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal, regardless of age or additional biologic features 2. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status

- INSS stage 4 and:

1. MYCN amplification, regardless of age or additional biologic features 2. Age > 18 months (> 547 days) regardless of biologic features

3. Age 12 - 18 months (365 - 547 days) with any of the following three

unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index =1) or any biologic feature that is indeterminant/unknown

- Children at least 365 days initially diagnosed with: INSS stage 1, 2, 4S who

progressed to a stage 4 without interval chemotherapy.

- Histologic proof of neuroblastoma or positive bone marrow for tumor cells with

increased urine catecholamines.

- Adequate renal and hepatic function (serum creatinine <3 x upper limit of normal for

age, AST< 3 x upper limit of normal).

- No prior therapy, unless an emergency situation requires local tumor treatment

(discuss with principal investigator).

- Written, informed consent according to institutional guidelines.

PARTICIPANT Exclusion Criteria:

- Any evidence, as judged by the investigator, of severe or uncontrolled systemic

disease (e. g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).

- Pregnant or breast feeding (female of child-bearing potential).

- Children with INSS 4 disease, age <18 months with all 3 favorable biologic features

(non-amplified MYCN, favorable pathology and DNA index >1). DONOR Inclusion Criteria:

- Potential donor is a biologic parent

- Potential donor is at least 18 years of age.

Locations and Contacts

Wayne L. Furman, MD, Phone: 866-278-5833, Email: info@stjude.org

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States; Recruiting
Wayne L. Furman, MD, Phone: 866-278-5833, Email: info@stjude.org
Wayne L. Furman, MD, Principal Investigator
Additional Information

St. Jude Children's Research Hospital

Clinical Trials Open at St. Jude

Starting date: May 2013
Last updated: April 10, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017