Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed or Refractory High-Risk NBL.

NCT00874315 | Withdrawn Phase 2 DMC

• 3 other identifiers: CDR0000636111NCH-08-0234IRB-2008-0230
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

RATIONALE: - Relapsed or refractory Neuroblastoma (NBL) carries a very poor prognosis and children with relapsed NBL have an overall 3 year survival rate of \< 10%. Hematopoietic Stem Cell Transplant from a different donor (allogeneic), is a form of adoptive cellular therapy , such that infused donor cells find host tumors as foreign and fight them. After transplant, the donor immune cells (i.e. T cells, NK cells) mediate Graft versus Tumor (GVT) effect and may stop tumor from recurring. Also,reduced intensity transplants lead to minimal toxicity and less risk of mortality in heavily pre-treated NBL patients. PURPOSE: This phase II trial is studying how well giving a reduced intensity(using Fludarabine, Busulfan and antithymocyte globulin)preparative regimen followed by donor stem cell transplant works in treating young patients with high-risk neuroblastoma that has relapsed or not responded to treatment.

Conditions

Neuroblastoma

Keywords

recurrent or refractory neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Feasibility as measured by the incidence of donor engraftment, transplant-related mortality, and grade III-IV acute graft-vs-host disease (GVHD) at day 100 and the incidence of extensive chronic GVHD within the first year post-transplantation

  The safety and feasibility of reduced intensity allogeneic HSCT will be established in this population by monitoring the incidence of adverse events- 100 day mortality,incidence of severe acute GVHD and non-engraftment of donor cells.

  100 days post-HSCT

Secondary Outcomes (3)

• Progression-free survival (PFS) at 1 year

  1 year post- HSCT

• Relationship between biologic endpoints (e.g., number of natural killer [NK] cells infused, NK cell recovery, and NK cell chimerism status) and clinical endpoints (e.g., donor engraftment, acute GVHD, transplant-related mortality, and PFS)

  3 and 6 months post-SCT

• Relationship between presence of killer immunoglobulin-like receptor (KIR) mismatches and clinical endpoints

  3 and 6 months post-HSCT

Interventions

anti-thymocyte globulin OTHER

2.5 mg/kg/day for 4 doses on day -3, -2 , -1 and day +2.

Also known as: Thymoglobulin

busulfan DRUG

0.8 mg/kg/dose for total of 8 doses.

Also known as: Busulfex

cyclosporine DRUG

1.5 mg/kg/dose every 12 hours.

Also known as: Sandimmune, Gengraf, Neoral.

fludarabine phosphate DRUG

30 mg/m2/day for 5 days.

Also known as: Fludara

mycophenolate mofetil DRUG

15 mg/kg/dose every 8 hours

Also known as: Cell-cept

tacrolimus DRUG

0.03 mg/kg/day as continuous infusion or 12 hour divided doses

allogeneic hematopoietic stem cell transplantation PROCEDURE

Donor stem cell transplantation from HLA matched sibling donor or an unrelated donor.

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of high-risk neuroblastoma, meeting one of the following criteria: * Refractory disease, defined as no response, mixed response, or progressive disease after completion of induction therapy administered according to clinical trials COG-A3973 or COG-ANBL0532 (or other similar high-intensity induction regimen) * Relapsed following high-dose chemoradiotherapy including autologous stem cell transplantation * Achieved a complete remission (CR), very good partial remission (VGPR), or partial remission (PR) after ≤ 2 different salvage regimens, as defined by the following: * In CR after treatment with some form of salvage therapy (e.g., ¹³¹I-MIBG, antibody-based therapy, or any other COG or NANT salvage-therapy regimen) * In VGPR or PR after salvage therapy * No more than 3 sites of skeletal disease as determined by an ¹²³I-MIBG scan (for regional involvement of the skeleton \[e.g., pelvis, spine\], the tumor involvement should be \< 25% of the site) * Bone marrow involvement (\< 25% neuroblasts) by morphologic exam within the past 2 weeks * Patients with soft tissue disease are eligible provided they exhibit either a VGPR or PR in the primary soft tissue mass and in any sites of metastatic soft tissue disease * Disease status meeting one of the following criteria: * Minimal residual disease * Disease considered responsive to a salvage regimen * Stable disease * No rapidly progressive disease * Donors must meet one of the following criteria: * Matched, related donor (6/6 or 5/6) (bone marrow donor allowed) * HLA-matched unrelated donor (10/10 match on high-resolution \[HR\] typing of HLA-A, B, C, DRB1, and DQB1) * One allele- or antigen-mismatched unrelated donor (9/10 match on HR typing), mismatched at HLA-C only * One allele- or antigen-mismatched unrelated donor (9/10 match on HR typing), mismatched at HLA-A, B, DRB1, or DQB1 (only when HLA-C mismatch is not available) PATIENT CHARACTERISTICS: * Karnofsky/Lansky performance status 60-100% * ANC \> 500/mm\^3 * Creatinine clearance or radioisotope GFR ≥ 60 mL/min * Total bilirubin \< 3.0 mg/dL * AST or ALT \< 5 times upper limit of normal * Shortening fraction ≥ 25% by ECHO OR ejection fraction \> 30% by MUGA * FEV\_1 and DLCO ≥ 30% OR normal chest x-ray, pulse oximetry, and venous blood gas * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * No active or recent (within the past 30 days) fungal infection * No proven or suspected sepsis, pneumonia, or meningitis unless appropriate therapeutic measures have been initiated to control the infection and systemic signs are no longer life-threatening * No requirement for oxygen or ventilator support PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior tandem autologous stem cell transplantations (according to clinical trial COG-ANBL0532) allowed * No prior allogeneic hematopoietic stem cell transplantation * More than 2 months since prior autologous stem cell transplantation, myeloablative therapy, total-body irradiation, whole abdominal radiotherapy, or therapeutic ¹³¹I-MIBG * More than 3 weeks since prior chemotherapy, immunotherapy (including anti-GD2 regimen), or biologic response modifiers and recovered * More than 2 weeks since prior local radiotherapy to the sites of metastatic disease

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (4)

Children's Memorial Hospital

Chicago, Illinois, United States

Location

Morgan Stanley Children's Hospital of NY

New York, New York, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hopsital of Wisconsin

Milwaukee, Wisconsin, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Recurrence

Interventions

Antilymphocyte Serum; thymoglobulin; Busulfan; Cyclosporine; Cyclosporins; fludarabine phosphate; Mycophenolic Acid; Tacrolimus

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Sandeep Soni, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2009
• First Posted: April 2, 2009
• Study Start: September 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: October 16, 2015

Record last verified: 2015-10

Locations

US (4)