Myeloablative Consolidation Therapy and Tandem Autologous Stem Cell Rescue in Patients With High-Risk Neuroblastoma

• ClinicalTrials.gov Identifier: NCT02605421
• Recruitment Status: Recruiting
• First Posted: November 16, 2015
• Last Update Posted: November 3, 2022
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

Study Description

Brief Summary:

This is a phase II single center study to administer two courses of myeloablative consolidation chemotherapy each followed by an autologous peripheral blood stem cell (PBSC) rescue in patients with high-risk neuroblastoma who have completed induction chemotherapy (independent of this study). Ideally, patients should begin consolidation chemotherapy no later than 8 weeks after the start of Induction Cycle #5; however it is strongly recommended to begin consolidation within 4-6 weeks after the start of Induction Cycle #5.

Condition or disease	Intervention/treatment	Phase
Neuroblastoma	Drug: Thiotepa; Drug: Cyclophosphamide; Drug: Melphalan; Drug: Etoposide; Drug: Carboplatin; Biological: Autologous Stem Cell Infusion; Biological: Granulocyte colony stimulating factor	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tandem Myeloablative Consolidation Therapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma
• Actual Study Start Date: June 2016
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: July 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Patients Treated for Neuroblastoma; Consolidation course #1 consists of thiotepa and cyclophosphamide followed by a PBSC rescue. Consolidation course #2 consists of melphalan, etoposide and carboplatin followed by a second PBSC rescue. Post infusion, patients will receive Granulocyte-Colony Stimulating Factor beginning on Day 0 of each consolidation course.

Drug: Thiotepa; Thiotepa by IV once daily for 3 doses on Days -7, -6 and -5. Given as part of Consolidation Course #1 along with Cyclophosphamide.; Drug: Cyclophosphamide; Cyclophosphamide by IV once daily for 4 doses on Days -5, -4, -3 and -2. Given as part of Consolidation Course #1 along with Thiotepa.; Drug: Melphalan; Melphalan by IV once daily for 3 doses on Days -8, -7, and -6. Given as part of Consolidation Course #2 along with Etoposide and Carboplatin.; Drug: Etoposide; Etoposide by IV once daily for 4 doses on Days -8, -7, -6 and -5. Given as part of Consolidation Course #2 along with Melphalan and Carboplatin.; Drug: Carboplatin; Carboplatin by IV once daily for 4 doses on Days -8, -7, -6 and -5. Given as part of Consolidation Course #2 along with Etoposide and Melphalan.; Biological: Autologous Stem Cell Infusion; On Day 0 the stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.; Biological: Granulocyte colony stimulating factor; Beginning on day 0 after infusion of the PBSC, patients will receive G-CSF SQ or IV (SQ preferred) 5 micrograms/kg once daily and continuing once daily until post-nadir ANC > 2000/μL for 3 consecutive days.; Other Name: G-CSF

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: 3 years from first PBSC infusion ]
   Percentage of patients with progression free survial. Kaplan-Meier curves and 95% confidence intervals will be used to estimate.

Secondary Outcome Measures :

1. Time to Engraftment [ Time Frame: Day 42 ]
   Defined as an absolute neutrophil count (ANC) greater than or equal to 0.5 x 109/L for three consecutive days by day 42 after first transplant.
2. Relapse [ Time Frame: 3 years from first PBSC infusion ]
   Percentage of patients with relapse. Relapse will be defined as any new lesion; increase of any measurable lesion by >25%; previous negative bone is positive.
3. Overall Survival [ Time Frame: 3 years from first PBSC infusion ]
   Kaplan-Meier curves and 95% confidence intervals will be used to estimate overall survival.

Eligibility Criteria

• Ages Eligible for Study: up to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• Less than 30 years of age at diagnosis of neuroblastoma
• End of Induction disease evaluation demonstrating CR, PR, MR or SD
• Hematopoietic Recovery from last induction course of chemotherapy
• No uncontrolled infection
• Minimum frozen PBSCs of 2 x 10^6 CD34 cells/kg for each transplant are mandatory and a PBSC of 2 x 10^6 CD34 cells/kg for back-up are strongly recommended (thus, PBSC of no less than 6 x 10^6 CD34 cells/kg is encouraged). These must all be collected prior to the initiation of consolidation.

• Adequate organ function defined as:

  • Hepatic: AST and ALT < 3 x upper limit of institutional normal; ALT ≤ 3 x ULN for age; total bilirubin ≤ 1.5 x ULN for age, if baseline was normal, > 1.0 1.5 x baseline if baseline was abnormal
  • Cardiac: shortening fraction ≥ 27% or ejection fraction ≥ 45%, no clinical congestive heart failure
  • Pulmonary: no evidence of dyspnea at rest and norequirement for supplemental oxygen
  • Renal: Creatinine clearance or GFR > 60 mL/min/1.73m^2. If a creatinine clearance is performed at end induction and the result is < 100 ml/min/1.73m^2, a GFR must then be performed using a nuclear blood sampling method or iothalamate clearance method. Camera method is NOT allowed as measure of GFR prior to or during Consolidation therapy for patients with GFR or creatinine clearance of < 100 ml/min/1.73m^2
• Recovery from acute toxicities of last cycle of induction chemotherapy
• Appropriate written consent - adult or parent/guardian if patient is < 18 years of age and minor information sheet if patient is > 8 years of age

Contacts and Locations

Contacts

Contact: Lisa Burke; 612-273-8482; lburke3@Fairview.org

Contact: Ashish Gupta, MBBS, MPH; 612-626-2961; stef0030@umn.edu

Locations

United States, Minnesota

Masonic Cancer Center, University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Lisa Burke, RN 612-273-8482 lburke3@Fairview.org

Principal Investigator: Ashish Gupta, MBBS, MPH

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Ashish Gupta, MBBS, MPH; Masonic Cancer Center, University of Minnesota

More Information

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT02605421
• Other Study ID Numbers: 2015LS108
• First Posted: November 16, 2015
• Last Update Posted: November 3, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Masonic Cancer Center, University of Minnesota:

High-risk neuroblastoma; Neuroblastoma; Myeloablative chemotherapy; Myeloablative consolidation chemotherapy; Autologous peripheral blood stem cell rescue; PBSC; Autologous stem cell rescue

Additional relevant MeSH terms:

Neuroblastoma; 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; Cyclophosphamide; Melphalan; Thiotepa; Carboplatin; Etoposide; Lenograstim; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Adjuvants, Immunologic