IRB Study Number 25-283
Status Recruiting
Phase Phase 3
Institute Taussig Cancer Institute
Description
1.1 Primary Objectives
1.1.1 To determine if the event-free survival (EFS) of patients with newly diagnosed high-risk neuroblastoma assigned to early chemoimmunotherapy during Induction differs from that of patients who are not assigned to treatment that includes early chemoimmunotherapy
1.2 Secondary Objectives
1.2.1 To determine if early chemoimmunotherapy during Induction therapy improves end of Induction (EOI) response rates and overall survival (OS) for patients with newly diagnosed high-risk neuroblastoma
1.2.2 To determine response rates, EFS, and OS following an Extended Induction regimen with chemoimmunotherapy in patients with progressive disease or a poor response to Induction therapy
1.2.3 To compare the toxicities experienced by patients treated with chemoimmunotherapy during Induction versus those experienced by patients treated with standard Induction and to describe toxicities experienced during Extended Induction
1.2.4 To determine GD2 expression on tumor tissue and tumor cells in bone marrow and assess for associations with response and outcome
Inclusion Criteria
3.2.1 Enrollment on APEC14B1
Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131.
3.2.2 Age
≤ 30 years at the time of initial diagnosis with high-risk disease 3.2.3 Diagnosis
i. Must have a diagnosis of NBL or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
ii. Newly diagnosed, HRNBL defined as one of the following:
a. Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M and MYCN amplification
b. Age ≥ 547 days and INRG Stage M regardless of biologic features (clinical MYCN testing not required prior to enrollment)
c. Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to Stage M without systemic
chemotherapy
d. Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to Stage M without systemic chemotherapy (clinical MYCN testing not required prior to enrollment)
See Appendix III for INRG Staging System.
See Section 3.1.3.2 for MYCN testing requirements to determine eligibility (if required to satisfy eligibility requirement) and information on central review of MYCN testing results that will occur through APEC14B1.
3.2.4 BSA
Patients must have a BSA ≥ 0.25 m2
3.2.5 Prior Therapy
• No prior anti-cancer therapy except as outlined below: o Patients initially recognized to have high-risk disease treated with topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing, and with consent as described in Section 3.1.5.
o Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (eg, as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease but subsequently found to meet the criteria in Section 3.2.3.
o Patients who received localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis.
3.2.6 HIV
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
3.2.7 Organ Function Requirements
3.2.7.1 Adequate renal function defined as:
A serum creatinine based on age/sex as follows: (See protocol)
OR - a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m2
OR - a GFR ≥ 70 mL/min/1.73 m2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard). Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
3.2.7.2 Adequate liver function defined as:
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
SGPT (ALT) ≤ 10 x ULN Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
3.2.7.3 Adequate cardiac function defined as:
Shortening fraction of ≥ 27% by echocardiogram, or
Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram.
3.2.7.4 Ability to tolerate Peripheral Blood Stem Cell (PBSC) Collection:
No known contraindication to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
Exclusion Criteria
3.2.8 Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features.
3.2.9 Patients ≥547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features.
3.2.10 Patients with known bone marrow failure syndromes.
3.2.11 Patients on chronic immunosuppressive medications (eg, tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable.
3.2.12 Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy.
3.2.13 Pregnancy and Breastfeeding
3.2.13.1 Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required prior to enrollment for female patients of childbearing potential.
3.2.13.2 Lactating females who plan to breastfeed their infants.
3.2.13.3 Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
3.2.14 Regulatory Requirements
3.2.14.1 All patients and/or their parents or legal guardians must sign a written informed consent.
3.2.14.2 All institutional, FDA, and NCI requirements for human studies must be met.
