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A Phase I study of gemtuzumab ozogamicin (GO) in combination with busulfan and cyclophosphamide (Bu/Cy) and allogeneic stem cell transplantation in children with poor-risk CD33+ AML: a new targeted immunochemotherapy myeloablative conditioning (MAC) regimen.
Biol Blood Marrow Transplant. 2012 Feb; 18(2):324-9.BB

Abstract

Children with high-risk acute myelogenous leukemia (AML) (induction failure [IF], refractory relapse [RR], third complete remission [CR3]) have dismal outcomes. Over 80% of AML patients express CD33, a target of gemtuzumab ozogamicin (GO). GO is an active drug in childhood AML but has not been studied in a myeloablative conditioning regimen. We sought to determine the safety of GO in combination with busulfan/cyclophosphamide (Bu/Cy) conditioning before allogeneic hematopoietic stem cell transplantation (alloSCT). GO was administered on day -14 at doses of 3.0, 4.5, 6.0, and 7.5 mg/m(2), busulfan on days -7, -6, -5, -4 (12.8-16.0 mg/kg), and cyclophosphamide on days -3 and -2 (60 mg/kg/day). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. We enrolled 12 patients: 8 IF, 3 RR, 1 CR3; median age: 3 years (1-17); median follow-up: 1379 days (939-2305). Nine received umbilical cord blood (UCB), 2 matched unrelated donors (MUDs) and 1 HLA-matched sibling donor: 3 patients each at GO doses of 3.0, 4.5, 6.0, or 7.5 mg/m(2). No dose-limiting toxicities secondary to GO were observed. Day 100 treatment-related mortality (TRM) was 0%. Myeloid and platelet engraftment was observed in 92% and 75% of patients at median day 22 (12-40) and 42 (21-164), respectively. Median day +30 donor chimerism was 99% (85%-100%). The probability of grade II-IV acute graft-versus-host disease (aGVHD) was 42% and chronic GVHD (cGVHD) was 28%. One-year overall survival (OS) and event-free survival (EFS) was 50% (95% confidence interval [CI], 20.8-73.6). GO combined with Bu/Cy regimen followed by alloSCT is well tolerated in children with poor-risk AML. GO at 7.5 mg/m(2) in combination with Bu/Cy is currently being tested in a phase II study.

Authors+Show Affiliations

Department of Pediatric, New York Presbyterian Morgan Stanley Children's Hospital, Columbia University, New York, NY, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22079471

Citation

Satwani, Prakash, et al. "A Phase I Study of Gemtuzumab Ozogamicin (GO) in Combination With Busulfan and Cyclophosphamide (Bu/Cy) and Allogeneic Stem Cell Transplantation in Children With Poor-risk CD33+ AML: a New Targeted Immunochemotherapy Myeloablative Conditioning (MAC) Regimen." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 18, no. 2, 2012, pp. 324-9.
Satwani P, Bhatia M, Garvin JH, et al. A Phase I study of gemtuzumab ozogamicin (GO) in combination with busulfan and cyclophosphamide (Bu/Cy) and allogeneic stem cell transplantation in children with poor-risk CD33+ AML: a new targeted immunochemotherapy myeloablative conditioning (MAC) regimen. Biol Blood Marrow Transplant. 2012;18(2):324-9.
Satwani, P., Bhatia, M., Garvin, J. H., George, D., Dela Cruz, F., Le Gall, J., Jin, Z., Schwartz, J., Duffy, D., van de Ven, C., Foley, S., Hawks, R., Morris, E., Baxter-Lowe, L. A., & Cairo, M. S. (2012). A Phase I study of gemtuzumab ozogamicin (GO) in combination with busulfan and cyclophosphamide (Bu/Cy) and allogeneic stem cell transplantation in children with poor-risk CD33+ AML: a new targeted immunochemotherapy myeloablative conditioning (MAC) regimen. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 18(2), 324-9. https://doi.org/10.1016/j.bbmt.2011.11.007
Satwani P, et al. A Phase I Study of Gemtuzumab Ozogamicin (GO) in Combination With Busulfan and Cyclophosphamide (Bu/Cy) and Allogeneic Stem Cell Transplantation in Children With Poor-risk CD33+ AML: a New Targeted Immunochemotherapy Myeloablative Conditioning (MAC) Regimen. Biol Blood Marrow Transplant. 2012;18(2):324-9. PubMed PMID: 22079471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Phase I study of gemtuzumab ozogamicin (GO) in combination with busulfan and cyclophosphamide (Bu/Cy) and allogeneic stem cell transplantation in children with poor-risk CD33+ AML: a new targeted immunochemotherapy myeloablative conditioning (MAC) regimen. AU - Satwani,Prakash, AU - Bhatia,Monica, AU - Garvin,James H,Jr AU - George,Diane, AU - Dela Cruz,Filemon, AU - Le Gall,John, AU - Jin,Zhezhen, AU - Schwartz,Joseph, AU - Duffy,Deirdre, AU - van de Ven,Carmella, AU - Foley,Sandra, AU - Hawks,Ria, AU - Morris,Erin, AU - Baxter-Lowe,Lee Ann, AU - Cairo,Mitchell S, Y1 - 2011/11/09/ PY - 2011/06/14/received PY - 2011/11/01/accepted PY - 2011/11/15/entrez PY - 2011/11/15/pubmed PY - 2012/5/9/medline SP - 324 EP - 9 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 18 IS - 2 N2 - Children with high-risk acute myelogenous leukemia (AML) (induction failure [IF], refractory relapse [RR], third complete remission [CR3]) have dismal outcomes. Over 80% of AML patients express CD33, a target of gemtuzumab ozogamicin (GO). GO is an active drug in childhood AML but has not been studied in a myeloablative conditioning regimen. We sought to determine the safety of GO in combination with busulfan/cyclophosphamide (Bu/Cy) conditioning before allogeneic hematopoietic stem cell transplantation (alloSCT). GO was administered on day -14 at doses of 3.0, 4.5, 6.0, and 7.5 mg/m(2), busulfan on days -7, -6, -5, -4 (12.8-16.0 mg/kg), and cyclophosphamide on days -3 and -2 (60 mg/kg/day). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. We enrolled 12 patients: 8 IF, 3 RR, 1 CR3; median age: 3 years (1-17); median follow-up: 1379 days (939-2305). Nine received umbilical cord blood (UCB), 2 matched unrelated donors (MUDs) and 1 HLA-matched sibling donor: 3 patients each at GO doses of 3.0, 4.5, 6.0, or 7.5 mg/m(2). No dose-limiting toxicities secondary to GO were observed. Day 100 treatment-related mortality (TRM) was 0%. Myeloid and platelet engraftment was observed in 92% and 75% of patients at median day 22 (12-40) and 42 (21-164), respectively. Median day +30 donor chimerism was 99% (85%-100%). The probability of grade II-IV acute graft-versus-host disease (aGVHD) was 42% and chronic GVHD (cGVHD) was 28%. One-year overall survival (OS) and event-free survival (EFS) was 50% (95% confidence interval [CI], 20.8-73.6). GO combined with Bu/Cy regimen followed by alloSCT is well tolerated in children with poor-risk AML. GO at 7.5 mg/m(2) in combination with Bu/Cy is currently being tested in a phase II study. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/22079471/A_Phase_I_study_of_gemtuzumab_ozogamicin__GO__in_combination_with_busulfan_and_cyclophosphamide__Bu/Cy__and_allogeneic_stem_cell_transplantation_in_children_with_poor_risk_CD33+_AML:_a_new_targeted_immunochemotherapy_myeloablative_conditioning__MAC__regimen_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(11)00476-9 DB - PRIME DP - Unbound Medicine ER -