More high-dose 3F8 trials open, one 3F8 trial closed

Memorial-Sloan Kettering (MSKCC) has opened two more high-dose 3F8 trials for neuroblastoma

High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Consolidation of Second or Greater Remission of High-Risk Neuroblastoma

(will accrue 63 patients)

High-Dose 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid for Primary Refractory Neuroblastoma in Bone Marrow

(will accrue 53 patients)

MSKCC is now offering four phase 2 high-dose 3F8 trials, two for frontline therapy with and without stem cell transplant, and two for relapse and refractory neuroblastoma.

These all use high dose 3F8 (80 mg/m2/day) for 4 cycles and lower dose 3F8 (20 mg/m2/d) for remaining cycles, and all trials include Accutane (13-cis-retinoic acid) and GM-CSF.

3F8 versus 13-cis-retinoic acid randomized trial just closed due to lack of enrollment

A Study of MAb-3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus 13-cis-Retinoic Acid (RA) Plus GM-CSF in Primary Refractory Neuroblastoma Patients

Lack of enrollment is cited for the reason this trial closed, which opened August 2009. This trial randomized primary refractory neuroblastoma patients to either 3F8 or 13-cis-retinoic acid, as opposed to giving the two agents together. This trial was sponsored by United Therapeutics and the goal was to obtain FDA approval for 3F8. More information is available in article posted here July 25, 2010.

Other 3F8 trials

Beta-Glucan and Monoclonal Antibody in Treating Patients With Metastatic Neuroblastoma

This phase 1 study using barley-derived beta-glucan for relapsed or refractory opened in 2001 with a planned accrual of 24 patients within 2 years. An abstract with results was presented at ASCO in 2007.[1]

From the abstract:

Fourteen children completed 1 cycle, 4 had 2 cycles, 2 had 3, and 6 had 4 cycles. Wleven patients had stable disease and 13 had progressive disease. Six children had elevated HAMA that caused withdrawal from the study.

14/23 patients with positive MIBG scans prior to therapy demonstrated improvement after one cycle. Responses did not correlate with BG dose received. 7 patients, all with residual disease survive at a median of 40 (range 24–45) months post-treatment. Conclusions: 3F8/BG is well tolerated and shows activity against resistant NB. Further clinical investigation of this novel combination is warranted.

Phase I Study of Oral Yeast β-Glucan and Intravenous Anti-GD2 Monoclonal Antibody 3F8 Among Patients With Metastatic Neuroblastoma

This study using a yeast beta-glucan opened in 2005 with a planned accrual of 42. It is currently listed as not recruiting participants.

Phase II Study of Anti-GD2 3F8 Antibody and Biologic Response Modifiers for High-Risk Neuroblastoma

This phase 2 study using beta-glucan opened in 2004 and was to accrue 74 patients. It was listed as completed in 2007, and no abstracts or publications yet.

Monoclonal Antibody 3F8 and Sargramostim (GM-CSF) in Treating Patients With Neuroblastoma

This study opened in 2003 with a projected accrual of 325. It is listed as still open and accruing, but with the high-dose trials just opening for patients with the same eligibility criterial I suspect it will be terminated soon if not already.

References

1.  Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 9566