Ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (GA101) (iFCG) for previously untreated patients with chronic lymphocytic leukemia (CLL) with mutated IGHV and non-del (17p).

Authors

Nitin Jain

Nitin Jain

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX

Nitin Jain , Philip A. Thompson , Jan Andreas Burger , Gautam Borthakur , Prithviraj Bose , Zeev Estrov , Alessandra Ferrajoli , Varsha Gandhi , William Plunkett , Wanda Lopez , Hagop M. Kantarjian , Susan Mary O'Brien , Michael J. Keating , William G. Wierda

Organizations

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, The University of Texas MD Anderson Cancer Center, Houston, TX, The University of Texas MD Anderson Cancer Center, Department of Leukemia, Houston, TX, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, University of California Irvine, Irvine, CA

Research Funding

Pharmaceutical/Biotech Company

Background: Pts with mutated IGHV (IGHV-M) have favorable long-term outcomes after FCR. Methods: We designed an investigator-initiated phase II trial with ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) for previously untreated pts with IGHV-M CLL (NCT02629809). The intent was to limit FC to 3 courses, potentially reducing short- and long-term toxicity, while maintaining efficacy through addition of ibrutinib and obinutuzumab. Key eligibility included age ≥18, IGHV-M, no del17p. Pts received 3 courses of iFCG. G-CSF was not mandated. Primary endpoint: CR/CRi with bone marrow (BM) MRD-neg (4-color flow-cytometry) after 3 courses of iFCG. Pts meeting primary endpoint received ibrutinib with obinutuzumab (iG) for C3-6, then ibrutinib C7-12. Pts not achieving primary endpoint received iG (C4-12). All pts who are MRD neg at 1 year will stop all therapy, including ibrutinib. Pts MRD+ at 1 year may continue ibrutinib. Historic C3 BM MRD-neg with FCR in IGHV-M 26% (Strati, Blood 2014). Target BM MRD-neg after iFCG x3 is 45%. Sample size 45. Results: 23 pts started treatment. Median age 59 yrs (25-71). Prognostic markers [del13q (n=17), negative (n=3); trisomy 12 (n=3)]. 18 pts completed 3 courses of iFCG and had initial response assessment (the remaining 5 pts too early). All 18 pts had a response; 14/18 (78%) achieved MRD-neg in BM at 3 month with 7/18 achieving CR/CRi (all MRD neg). No pt has progressed, and all but one continue to receive treatment. Of the 23 pts, 11 pts had G3-4 neutropenia and 5 pts had G3-4 thrombocytopenia. 4 pt had neutropenic fever. 1 pt who achieved MRD-neg CR developed pulmonary MAC infection, and declined further therapy. 1 pt had atrial fibrillation. G3 ALT developed in 3 pts. FC was dose reduced in 10 pts; ibrutinib dose-reduced in 2 pts. Conclusions: iFCG achieves high rate of MRD-neg remission after 3 courses. Pt enrollment continues, and updated results will be presented at the ASCO meeting. Clinical trial information: NCT02629809

Response at 3 Month
Best Response
N=18Marrow MRDN=18Marrow MRD
ORR18/18 (100)14/18 (78) neg18/18 (100)16/18 (89) neg
CR/CRi7 (39)7/7 (100) neg9 (50)9/9 (100) neg
PR11 (61)7/11 (64) neg9 (50)7/9 (78) neg

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Track

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Sub Track

Chronic Lymphocytic Leukemia (CLL) and Hairy Cell

Clinical Trial Registration Number

NCT02629809

Citation

J Clin Oncol 35, 2017 (suppl; abstr 7522)

DOI

10.1200/JCO.2017.35.15_suppl.7522

Abstract #

7522

Poster Bd #

284

Abstract Disclosures

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