Autologous Transplant Followed by Allogeneic Transplant for High Risk Neuroblastoma

NCT00670410 | Terminated Phase 1 DMC

• 2 other identifiers: AAAA7937CHNY-01-502
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Neuroblastoma is a malignant tumor of the sympathetic nervous system. It is the second most common malignant tumor of childhood. Although modest advances have been made over the past 20 years children with high-risk neuroblastoma continue to have an unsatisfactory long-term survival. This study will administer induction chemotherapy followed by high-dose (myeloablative) chemotherapy with autologous stem cell transplantation, followed by radiation therapy, then immunotherapy with a non myeloablative allogeneic stem cell transplant for treatment of neuroblastoma. The purpose of this clinical research trial is to study the feasibility of giving immunotherapy with a non-myeloablative allogeneic transplant (NAT/AlloSCT), following myeloablative therapy and autologous stem cell transplant (MAT/AutoSCT). This study will also determine the side effects as well as the response rate for each group of patients (treatment arm).

Conditions

Neuroblastoma

Keywords

Neuroblastoma; Autologous Transplant; Allogeneic Transplant; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Rate of engraftment following NAT/AlloSCT from either a related donor or umbilical cord donor.

  The distribution of the time to neutrophil and platelet engraftment following consolidation (myeloablative) and intensification (non-ablation) will be estimated using the product-limit method of the Kaplan and Meier.

  1 year

• Progression Free Survival (PFS) in patients with high-risk neuroblastoma receiving sequential MAT/AutoSCT and NAT/AlloSCT.

  Progression Free (PFS) will be estimated using the product limit method of Kaplan and Meier.

  5 years

• Overall Survival (OS) in patient with high-risk neuroblastoma receiving sequential MAT/AutoSCT and NAT/AlloSCT.

  Overall Survival (OS) will be estimated using the product limit method of Kaplan and Meier.

  5 years

Study Arms (2)

Arm A - Related Donor

EXPERIMENTAL

Related donor transplant: Patients with a related donor (5/6 or 6/6 HLA matched) will receive immunotherapy with a non-myeloablative preparative regimen of Busulfan and Fludarabine followed by allogeneic stem cell transplant (AlloSCT).

Procedure: Related donor transplant; Drug: Busulfan; Drug: Fludarabine

Arm B - Cord Blood Donor

EXPERIMENTAL

Unrelated cord blood transplant: Patients without a related donor will receive immunotherapy with a non-myeloablative preparative regimen of busulfan and fludarabine followed by allogeneic stem cell transplant (AlloSCT) with either an unrelated umbilical cord blood donor (4/6, 5/6, or 6/6 HLA matched), or a related umbilical cord blood donor (3/6, 4/6, 5/6, or 6/6 HLA matched). Patients will receive Thymoglobulin ((rabbit) Anti-Thymocyte Globulin (ATG)) during the preparative regimen. GVHD prophylaxis will be Tacrolimus and mycophenolate mofetil (MMF).

Procedure: Cord blood transplant; Drug: Busulfan; Drug: Thymoglobulin; Drug: Fludarabine

Interventions

Related donor transplant PROCEDURE

Patients with a related donor will get reduced intensity transplant conditioning with busulfan and fludarabine.

Arm A - Related Donor

Cord blood transplant PROCEDURE

Patients with a matched cord blood donor will get reduced intensity conditioning with busulfan, fludarabine, and ATG.

Arm B - Cord Blood Donor

Busulfan DRUG

Busulfan (Busulfex) \[4mg/kg/dose for patients \< 4 years; 3.2 mg/kg/dose for patients \> 4 years\] will be given IV in 0.9% sodium chloride or D5W to a final concentration \> 0.5 mg/mL solution for infusion equal to 10 times the volume of diluent to Busulfex, through a central venous access device over 3 hours once daily.

Also known as: Busulfex®

Arm A - Related Donor; Arm B - Cord Blood Donor

Thymoglobulin DRUG

Patients with an umbilical cord blood donor will also receive Thymoglobulin (ATG-rabbit) during the preparative regimen.

Also known as: ATG-rabbit

Arm B - Cord Blood Donor

Fludarabine DRUG

Fludarabine 30 mg/m2 x 5 days, total dose = 150 mg/m2. Patients \< 12 kg will receive Fludarabine 1 mg/kg x 5 days, total dose = 5 mg/kg. Fludarabine will be given IV in 100 ml (or to a concentration of 1 mg/mL) of D5W or 0.9% sodium chloride, and infused over 30 min on Days -6 to 2.

Also known as: Fludara®

Arm A - Related Donor; Arm B - Cord Blood Donor

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age be \< 30 years of age at the time of initial diagnosis.
• Patients must have a diagnosis of neuroblastoma (ICD-O morphology 9500/3) verified by histology and/or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria. The revised International Neuroblastoma Staging System (INSS) will be used to stage all patients 58. (See 14.3 for risk assignment).
• Patients with newly diagnosed neuroblastoma and age \> 547 days with the following:
• INSS Stage 4 neuroblastoma regardless of biologic factors
• INSS Stage 2A/2B with MYCN amplification (\> 10)
• INSS Stage 3 with MYCN amplification (\> 10) OR Unfavorable histology
• Patients with newly diagnosed neuroblastoma and age \< 365 days with the following:
• \* INSS Stage 3, 4, OR 4S neuroblastoma AND MYCN amplification (\> 10).
• Patients with newly diagnosed Neuroblastoma and age 365 - \<547 days with the following:
• INSS Stage 3 with MYCN amplification (\> 10)
• INSS Stage 4 with MYCN amplification (\> 10) OR with deoxyribonucleic acid (DNA) Index (ploidy) = 1 OR with Unfavorable histology
• Patients \> 365 days with INSS Stage 1, 2, and 4S who have progressed to Stage 4.
• Newly Diagnosed patients should be entered on this study within 4 weeks of diagnosis, or after receiving only one cycle of intermediate dose chemotherapy for patients initially treated on/according to the low or intermediate risk Children's Oncology Group (COG) neuroblastoma studies, or within 4 weeks of progression to Stage 4 for INSS Stage 1, 2, 4S.
• Patients treated with alternative induction regimens and/or consolidation regimens (AutoSCT) who were not enrolled at diagnosis but who achieve a complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) and meet all other criteria will be eligible for either the consolidation MAT/AutoSCT and NAT/AlloSCT immunotherapy or NAT/AlloSCT, which ever is clinically appropriate after discussion with the Principal Investigators.
• Liver Function: alanine aminotransferase (ALT) and bilirubin \< 3x normal

You may not qualify if:

• Patients who are pregnant. Patients of childbearing potential must practice an effective method of birth control while participating on this study.

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia Presbyterian Medical Center, Morgan Stanley Children's Hospital New York Presbyterian

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Busulfan; thymoglobulin; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Darrell Yamashiro, MD

  Columbia University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 1, 2008
• Study Start: November 1, 2003
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: June 24, 2016

Record last verified: 2016-06

Locations

US (1)