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

• Status: Withdrawn
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nationwide Children's Hospital
• Treatments: Antilymphocyte Serum; Busulfan; Cyclosporine; Cyclosporins; Fludarabine; Fludarabine phosphate; Mycophenolate mofetil; Mycophenolic Acid; Tacrolimus; Thymoglobulin

Criteria

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