Lymphoma Committee Alliance for Clinical Trials in Oncology 2016 Beijing International Lymphoma Conference April 9, 2016 David J. Straus, M.D.

Transcription

1 Lymphoma Committee Alliance for Clinical Trials in Oncology 2016 Beijing International Lymphoma Conference April 9, 2016 David J. Straus, M.D. Memorial Sloan Kettering Cancer Center New York, NY USA

2 CALGB/Alliance Cancer and Leukemia Group B (CALGB) Founded in 1956 Multidisciplinary, multimodality Funded by National Cancer Institute (US) Former Lymphoma Chairs Arlen Gottlieb, Bruce Peterson, Dan Longo, George Canellos, Bruce Cheson ( ), John Leonard (2013-present) Alliance for Clinical Trials in Oncology Founded 2011 Merger of CALGB, NCCTG, ACOSOG 10,000 specialist members US/Canada NCI National Clinical Trials Network

3 Alliance for Clinical Trials in Oncology Purpose: to reduce the impact of cancer by uniting a broad community of scientists and clinicians from many disciplines, committed to discovering, validating and disseminating effective strategies for the prevention and treatment of cancer Alliance achieves this purpose by conducting high quality multidisciplinary cancer control, prevention, and treatment trials that engage a comprehensive research network; furthering our understanding of the biological basis of the cancer process and its treatment, from discovery, to validation, to clinical practice; providing a scientific and operational infrastructure for innovative clinical and translational research in academic and community settings

4 Breast Respiratory Genitourinary Gastrointestinal Neuro- Oncology Leukemia Lymphoma Myeloma Surgical Oncology, Medical Oncology, Radiation Oncology, Pathology, Imaging, Oncology Nursing, Clinical Research Associates, Biostatistics, Bioinformatics, Information Systems, Pharmacology, Pharmacogenomics, Patient Advocates, Health Outcomes, Symptom Intervention, Experimental Therapeutics, Community Oncology, Research Ethics, Laboratory Medicine, Regulatory Affairs, Cancer Prevention, Special Populations Research 31 scientific committees 16 administrative committees 395 committee members

5 Study Design by Scientific and Modality Committees Study Operations NCTN logo NCI National Clinical Trials Network Alliance Foundation Trials

6 NCTN logo National Clinical Trials Network

7 National Clinical Trials Network 3,100 Institutions 14,000 Investigators

8 Member Institutions 136 Main Members 927 Affiliates/Components

9 Study Design by Scientific and Modality Committees Study Operations NCTN logo NCI National Clinical Trials Network Alliance Foundation Trials

10 Alliance for Clinical Trials in Oncology Foundation Not-for-Profit Corporation created to enhance and expand the ability of Alliance members* to conduct cancer clinical research 501(c)3: tax exempt Governance and operations structure separate from the Alliance Alliance Foundation Trials, LLC (AFT) Subsidiary organization created to conduct cancer clinical research involving partners other than the National Cancer Institute

11 Alliance Foundation: Contract Categories Alliance Foundation support of NCI studies Contracts between Alliance Foundation and outside parties for work in collaboration with NCI-funded initiatives Example: Contract with industry partner to fund correlative science projects for an NCI-funded trial Alliance Foundation Trials (AFT) Contracts between Alliance Foundation Trials, LLC and outside parties for work that does not involve NCI studies or NCI resources Examples: PCORI awards (Patient-Centered Outcomes Research Institute), Investigator-initiated industry-sponsored trials

12 Alliance Lymphoma Committee Leadership Chair John Leonard (Cornell) Bruce Cheson (Georgetown) Vice Chair Nancy Bartlett (Washington U) Pathology/Lymphoma Translational Science Eric Hsi (Cleveland Clinic) Imaging Heiko Schoder (MSKCC) Lale Kostakoglu (Mt. Sinai)

13 Alliance Lymphoma Committee Members Jeremy Abramson MGH Anne Beaven - Duke Kristie Blum Ohio State Bruce Cheson - Georgetown Sean Collins Georgetown Steven Horwitz - MSKCC Anthony Jaslowski - Community Lawrence Kaplan UCSF Lale Kostakoglu Mt. Sinai Ann LaCasce - Dana Farber/Partners Frederick Lansigan Datmouth Brian Link U of Iowa Kami Maddocks Ohio State Ben Marchello Community Benjamin Marchello _ Montana CC Peter Martin - Cornell Vicki Morrison - U of Minnesota Heiko Schoder - MSKCC Thomas Shea - U of North Carolina Sonali Smith U of Chicago David Straus MSKCC Chaitra Ujjani Georgetown Andrew Zelenetz - MSKCC

14 Alliance Lymphoma Trials Open to Accrual Protocol Number CALGB CALGB CALGB CALGB Study Title Phase II trial of response-adapted therapy based on positron emission tomography (PET) for bulky stage I and stage II classical Hodgkin lymphoma (HL) A randomized phase II trial of ofatumumab and bendamustine vs. ofatumumab, bortezomib and bendamustine in patients with untreated follicular lymphoma A randomized phase II trial of myeloablative versus non-myeloablative consolidation chemotherapy for newly diagnosed primary CNS B-cell lymphoma Natural killer cell KIR and HLA genotypes may predict response to antibody therapy in follicular lymphoma

15 Selected research highlights

16 US cooperative group risk-adapted Hodgkin Lymphoma clinical trials CALGB (non-bulky stage I/II) Intergroup: ASH abstract 2015 AVBD x 2 cycles PET scan PET- 2 more ABVD cycles PET+ 2 cycles escalated BEACOPP + IF RT CALGB (bulky stage I/II): Accruing ABVD x 2 cycles PET scan PET - 4 more ABVD cycles PET+ 4 cycles escalated BEACOPP + IF RT S0816 (stage III/IV) Intergroup: J Clin Oncol, in press, 2016 ABVD x 2 cycles PET scan PET - 4 more ABVD cycles PET+ 6 more escalated BEACOPP cycles

17 CALGB Progression Free Survival Post cycle 2 ABVD PET- and PET+ Patients Probability progression free PET-negative PET-positive N= 131 N= 13 Events= 8 Events= 4 p-value= Follow-up time Median: 2.1 years Range: < 1month 4.3 years 1 Death (Suicide PET +) Years from Study Entry Est. 3-yr PFS Hazard Ratio PET - 92% (84%-96%) 6.04 ( ) PET + 66% (32%-86%)

18 S0816 PFS by PET2 Result 100% Arm 1: Continued ABVD 80% 60% Arm 1: ebeacopp 40% 20% At Risk Failed 2-year Estimate All Patients at Risk Failed 2-Year Estimate PET-negative PET PET-postive negative % 61% 39 79% PET positive % 0% Months After Registration

19 DLBCL Comparison of CHOP-R and EPOCH-R R-CHOP Rituximab 375 mg/m 2 d1 Cyclophosphamide 750 mg/m2 d1 Doxorubicin 50 mg/m 2 d1 Vincristine 1.4 mg/m 2 (2 mg cap) d1 Prednisone 40 mg/m 2 d1-5 q3w 6 DA*-R-EPOCH Rituximab 375 mg/m 2 d1 Etoposide 50 mg/m 2 /d CI d1-4* Doxorubicin 10 mg/m 2 /d CI d1-4* Vincristine 0.4 mg/m 2 /d CI d1-4 Cyclophosphamide 750 mg/m 2 d5* Prednisone 60 mg/m 2 bid d1-4 G-CSF 5 μg/kg d6-anc recovery q3w 6 *Doses increased or decreased based on degree of neutropenia.

20 CALGB:50303 Phase III Randomized Study of R-CHOP v. DA-EPOCH-R with Microarray ARM A: R-CHOP Treatment completed C1 C2 C3 C4 C5 C6 Randomization Tumor Biopsy Blood Samples Stage Stage C1 C2 C3 C4 C5 C6 ARM B: DA-EPOCH-R Gene Expression Profiling GCB v ABC DLBCL Analysis Discovery Treatment completed if no change C5 to C7 staging Whole Genome Sequencing Germ line and Tumor Discovery Time Line (weeks)

21 50303 status Completed accrual 5/2013 Case review complete Assessing timeline for final clinical analysis Upgrading molecular profiling technology - High priority for NCI (Lou Staudt) - Resolving consent/ethical issues Many components (clinical, correlative, PET) Will probably be presented at ASH 2016 but need to confirm feasibility

22 A Molecular profiling-based therapy in recurrent DLBCL Relapsed/Refractory DLBCL-ABC Salvage PR, stem cells collected Randomization Stratify by time to relapse, conditioning regimen Arm A Arm B ASCT: CBV or BEAM + Ibrutinib 560 mg ASCT: CBV or BEAM Ibrutinib x 12 months Placebo x 12 months Follow Up Follow Up

23 Published Upfront FL studies Focus on non-chemotherapy regimens (Czuczman) Phase II R + Galiximab (anti-cd80) (Grant) Phase II R + Epratuzumab (anti-cd22) Under analysis (Martin) Phase II R + Lenalidomide Celgene has completed accrual of phase III vs standard chemoimmunotherapy (Rosenbaum) Phase II Ofatumumab (anti-cd20) Accruing (Blum) Phase II Benda/Ofatumumab +/- Bortezomib with maintenance R/RBort

24 Other areas A51101 (Batchelor) Primary CNS lymphoma Ph II myeloablative vs non-myeloablative (accruing slowly) A (Andreadis/Shea) Ibrutinib with ausct in DLBCL Alliance Foundation (Martin/Leonard/Smith) - Azacitidine + R-CHOP in DLBCL Alliance Foundation (Maddocks) Ibrutinib + palbociclib (CKI) Imaging - PET adapted therapy in Hodgkin Lymphoma - PET as surrogate for outcome in DLBCL, FL Correlative science - Molecular profiling in DLBCL (50303, 51301) - FcR polymorphisms with rituximab in FL (Byrd) - IHC markers in FL (Chadburn) - Serum markers in Hodgkin lymphoma (Hsi)

25 Plans and priorities Better assess and manage timelines of analysis and reporting of completed and companion studies (with data/statistical, translational, imaging and other team members) Collaborate effectively via LYSC and SWOG/ECOG members - High risk FL, High risk DLBCL, upfront MCL may be priorities - Advance initiatives in HL, T cell as opportunities allow - Focus on precision therapy, biomarkers, surrogates - Navigate intergroup collaborations Optimize industry partnerships - Capitalize on AFT mechanism Advance promising translational sciences (MRD, profiling) Continue to engage committee members and participating individuals, particularly junior investigators