Autologous Transplant Followed by Allogeneic Transplant for High Risk Neuroblastoma - Full Text View

Sponsored by:	Columbia University
Information provided by:	Columbia University
ClinicalTrials.gov Identifier:	NCT00670410

Purpose

HYPOTHESIS: The combination of high dose induction chemotherapy, followed by consolidation with myeloablative therapy (MAT) and autologous stem cell transplant (AutoSCT), followed by immunotherapy with non-myeloablative therapy (NAT) and allogeneic stem cell transplant (AlloSCT) from either a related donor or umbilical cord donor, will be well tolerated, and provide information to develop future randomized trials testing the role of NAT/AlloSCT in patients with high-risk neuroblastoma after undergoing MAT/AutoSCT.

Condition	Intervention	Phase
Neuroblastoma	Procedure: Related donor stem cell transplant Procedure: unrelated cord blood transplant	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Pilot Study of Sequential Autologous Stem Cell Transplantation and Immunotherapy With Reduced Intensity Allogeneic Stem Cell Transplant for High Risk Neuroblastoma

Resource links provided by NLM:

MedlinePlus related topics: Neuroblastoma

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:

To study the feasibility and toxicity of administering sequential MAT/AutoSCT and NAT/AlloSCT in patients with high-risk neuroblastoma. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
To determine the rate and durability of engraftment following NAT/AlloSCT from either a related donor or umbilical cord donor. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To determine the overall and disease free survival (DFS) of patients with high-risk neuroblastoma receiving sequential MAT/AutoSCT and NAT/AlloSCT. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the toxicity of a consolidation myeloablative chemotherapy of topotecan, carboplatin, and thiotepa. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
To determine the response rate of consolidation myeloablative chemotherapy of topotecan, carboplatin, and thiotepa in patients with measurable disease prior to MAT/AutoSCT. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
To determine the incidence of acute and chronic GVHD following NAT/AlloSCT and its relationship to DFS in patients with high-risk neuroblastoma. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To quantitate minimal residual disease status using immunocytochemistry, and RT PCR for GAGE and tyrosine hydroxylase. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To determine immune reconstitution after NAT/AlloSCT in patients with high-risk neuroblastoma. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	December 2002
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A: Experimental Related Donor	Procedure: Related donor stem cell transplant Patients with a related donor will get reduced intensity transplant conditioning with busulfan and fludarabine.
Arm B: Experimental Cord Blood donor	Procedure: unrelated cord blood transplant patients with an matched unrelated cord blood donor will get reduced intensity conditioning with busulfan, fludarabine, and ATG.

Detailed Description:

Despite the modest advances made over the past two decades with the addition of more intensive chemotherapy and high dose myeloablative therapy with allogeneic or autologous bone marrow transplantation, children with high-risk neuroblastoma continue to have an unsatisfactory long-term survival. The current survival for a child > 1 year of age at diagnosis with stage 4 neuroblastoma is only 20-35% 1,7. The overall treatment plan for high-risk patients with neuroblastoma will be: Induction Therapy Intensive induction chemotherapy with the cardioprotectant dexrazoxane (Zinecard), vincristine, doxorubicin (Adriamycin), and cyclophosphamide (ZVAC), alternating with cisplatin and etoposide (CiE). Patients who receive induction chemotherapy on an alternate protocol and achieve a CR, VGPR, or PR will also be eligible for entry to receive consolidation therapy and AlloSCT immunotherapy after discussion and approval of the Principal Investigators ). Consolidation Therapy with AutoSCT Consolidation therapy with a myeloablative preparative regimen of carboplatin, thiotepa, and topotecan (CaTT) followed by AutoSCT with PBSCs (CD34+ selection optional). Immunotherapy with Non-myeloablative AlloSCT Immunotherapy with a non-myeloablative preparative regimen of busulfan and fludarabine followed by AlloSCT with either: (Arm A) a related donor (5/6 or 6/6 HLA matched); or (Arm B) an umbilical cord blood donor (unrelated 4/6, 5/6, or 6/6 HLA matched, or related 3/6, 4/6, 5/6, or 6/6 HLA matched). Patients with an umbilical cord blood donor will also receive Thymoglobulin (ATG-rabbit) during the preparative regimen. GVHD prophylaxis will consist of Tacrolimus and mycophenolate mofetil (MMF). Maintenance Therapy Patients with a related donor who have persistent disease detected prior to NAT/AlloSCT will be assigned to Arm A1 and will receive two courses of DLI, followed by cis-RA for 6 cycles. Patients with a related donor with no persistent disease detected prior to NAT/AlloSCT will be assigned to Arm A2 and receive cis-RA for 6 cycles.

Patients with an umbilical cord blood donor will receive cis-RA for 6 cycles. Radiation Therapy Due to the potential risk of increased GVHD following radiation therapy, local radiation therapy to the primary tumor site (21 Gy) and metastatic sites, will be given after NAT/AlloSCT for patients on Arm A2 and Arm B, and prior to cis-RA therapy. Radiation therapy will be given following DLI in Arm A1, and prior to cis-RA therapy.

Eligibility

Ages Eligible for Study:	up to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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 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 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 CR, VGPR, PR, or 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: ALT and bilirubin < 3x normal
Cardiac Function: Shortening fraction > 27%, or ejection fraction > 47%, no clinical congestive heart failure.
Renal Function: Creatinine clearance and/or GFR > 60 ml/min/1.73m2.
Hematologic Function: Patients must have adequate hematopoietic function (ANC > 1000/mm3 and platelets > 100,000/mm3) unless inadequate hematopoiesis documented to be due to bone marrow involvement with tumor (> 10% tumor infiltration).

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670410

Locations

United States, New York
Columbia Presbyterian Medical Center, Morgan Stanley Children's Hospital New York Presbyterian
New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Investigators

Study Chair:

Darrell Yamashiro, MD

Columbia University

More Information

No publications provided

Responsible Party:	Columbia University ( John Ennever, MD, PhD/Director, Regulatory Knowledge and Support Resource )
Study ID Numbers:	CHNY-01-502, AAAA7937
Study First Received:	April 29, 2008
Last Updated:	May 14, 2009
ClinicalTrials.gov Identifier:	NCT00670410 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Columbia University:

Neuroblastoma
Autologous Transplant
Allogeneic Transplant
Immunotherapy

Study placed in the following topic categories:

Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Busulfan
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma

Fludarabine
Fludarabine monophosphate
Neuroectodermal Tumors, Primitive, Peripheral
Neuroblastoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neuroblastoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 03, 2009