David Rizzieri

Overview:

My research interests focus on the care of patients with hematologic malignancies, both with and without the use of bone marrow or stem cell transplantation. I focus my research efforts on new approaches to manipulate minimal residual disease.

Recent endeavors have included:

  1. Phase one trials with novel anti-cancer agents targeting aurora kinases, tyrosine kinases, mtor, VEGF, and raf/ras pathways 
  2. New monoclonal antibodies targeting tumor stroma rather than cellular antigens 
  3. Investigating new antibody targets, i.e. CD123, endoglin, or tenascin for hematologic malignancies 
  4. Aggressive therapy and transplantation for mantle cell lymphoma 
  5. Antiangiogenesis therapy for patients with NHL 
  6. Nonablative allogeneic transplantation therapy with matched or mismatched donors followed by immune modulation

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1991

University of Rochester

Medical Resident, Medicine

Duke University

Fellow in Hematology/Oncology, Medicine

Duke University

Grants:

Mechanisms of lung injury following autologous BMT

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

An Open Lavel, Multicenter, Extension Study for Subjects Who Participated in Prior Guadecitabine Clinical Studies

Administered By
Duke Cancer Institute
Awarded By
Astex Therapeutics Ltd.
Role
Principal Investigator
Start Date
End Date

An Open Label Phase IB study of PF-04449913 (Glasdegib) in Combination with Azacitidine in patients with previously untreated higher-risk myelodysplastic syndrome, acute myeloid leukemia

Administered By
Duke Cancer Institute
Awarded By
Pfizer, Inc.
Role
Principal Investigator
Start Date
End Date

A Multicenter, open-label treatment protocol of Gilteritinib (ASP2215) in patients with FMS-like Tyrosine Kinase 3 (FLT3) Mutated Relapsed or Refractory Acute Myeloid Leukemia (AMLJ) or FLT3-Mutated AML in Complete Remission (CR) with Mini ResiduaL

Administered By
Duke Cancer Institute
Awarded By
Astellas Pharma Inc.
Role
Principal Investigator
Start Date
End Date

A Phase 2 Open-Label, Multi-Center, Randomized, Controlled, Dose-Finding Study of DCC-UCB In Adults Receiving High Dose Chemotherapy For Acute Myleoid Leukemia

Administered By
Duke Cancer Institute
Awarded By
Nohla Therapeutics Inc.,
Role
Principal Investigator
Start Date
End Date

Publications:

Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study.

There is a significant need for improved therapeutics in older patients with acute leukemia. Camidanlumab tesirine is an antibody-drug conjugate against CD25, an antigen expressed in several malignancies, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This open-label, dose-escalation and -expansion study (NCT02588092) assessed the safety, activity, pharmacokinetics (PK), and immunogenicity of camidanlumab tesirine in patients with relapsed/refractory ALL/AML. A total of 35 patients (34 AML and 1 ALL) were enrolled and received camidanlumab tesirine intravenously at 3-92 μg/kg once every three weeks (Q3W, n = 26) or 30 or 37.5 μg/kg every week (QW, n = 9). One dose-limiting toxicity of maculopapular rash occurred in the 30 μg/kg QW group; the maximum tolerated dose was not reached. No additional safety concerns or adverse events (AEs) of interest were identified. The most common (>10 % of patients) Grade ≥3 treatment-emergent AEs were febrile neutropenia (25.7 %), lymphopenia, neutropenia, thrombocytopenia or fatigue (all 14.3 %), pneumonia, increased gamma-glutamyltransferase, and hypophosphatemia (each 11.4 %). No signal for serious immune-related AEs such as Guillain-Barré syndrome/polyradiculopathy was observed and there was no evidence of immunogenicity. PK showed rapid clearance with apparent half-life <2 days for conjugated and total antibody, suggesting that Q3W dosing may be insufficient for therapeutic efficacy, and prompting exploration of a QW schedule. Two patients achieved complete responses with incomplete hematologic recovery; one each at 30 and 37.5 μg/kg QW. The trial was terminated during dose escalation due to programmatic reasons other than safety. Hence, recommended dose was not determined.
Authors
Goldberg, AD; Atallah, E; Rizzieri, D; Walter, RB; Chung, K-Y; Spira, A; Stock, W; Tallman, MS; Cruz, HG; Boni, J; Havenith, KEG; Chao, G; Feingold, JM; Wuerthner, J; Solh, M
MLA Citation
Goldberg, Aaron D., et al. “Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study.Leuk Res, vol. 95, Aug. 2020, p. 106385. Pubmed, doi:10.1016/j.leukres.2020.106385.
URI
https://scholars.duke.edu/individual/pub1448601
PMID
32521310
Source
pubmed
Published In
Leuk Res
Volume
95
Published Date
Start Page
106385
DOI
10.1016/j.leukres.2020.106385

Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report.

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
Authors
Zhou, Z; Nath, R; Cerny, J; Wang, H-L; Zhang, M-J; Abdel-Azim, H; Agrawal, V; Ahmed, G; Al-Homsi, AS; Aljurf, M; Alkhateeb, HB; Assal, A; Bacher, U; Bajel, A; Bashir, Q; Battiwalla, M; Bhatt, VR; Byrne, M; Cahn, J-Y; Cairo, M; Choe, H; Copelan, E; Cutler, C; Damlaj, MB; DeFilipp, Z; De Lima, M; Diaz, MA; Farhadfar, N; Foran, J; Freytes, CO; Gerds, AT; Gergis, U; Grunwald, MR; Gul, Z; Hamadani, M; Hashmi, S; Hertzberg, M; Hildebrandt, GC; Hossain, N; Inamoto, Y; Isola, L; Jain, T; Kamble, RT; Khan, MW; Kharfan-Dabaja, MA; Kebriaei, P; Kekre, N; Khera, N; Lazarus, HM; Liesveld, JL; Litzow, M; Liu, H; Marks, DI; Martino, R; Mathews, V; Mishra, A; Murthy, HS; Nagler, A; Nakamura, R; Nathan, S; Nishihori, T; Olin, R; Olsson, RF; Palmisiano, N; Patel, SS; Patnaik, MM; Pawarode, A; Perales, M-A; Politikos, I; Popat, U; Rizzieri, D; Sandmaier, BM; Savani, BN; Seo, S; Shah, NN; Uy, GL; Valcárcel, D; Verdonck, LF; Waller, EK; Wang, Y; Weisdorf, D; Wirk, B; Wong, E; Yared, JA; Saber, W
MLA Citation
Zhou, Zheng, et al. “Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report.Blood Adv, vol. 4, no. 13, July 2020, pp. 3180–90. Pubmed, doi:10.1182/bloodadvances.2019001266.
URI
https://scholars.duke.edu/individual/pub1451639
PMID
32663298
Source
pubmed
Published In
Blood Adv
Volume
4
Published Date
Start Page
3180
End Page
3190
DOI
10.1182/bloodadvances.2019001266

Phase I dose escalation study of naive T-cell depleted donor lymphocyte infusion following allogeneic stem cell transplantation.

Prophylactic donor lymphocyte infusions (DLI) are used to augment post-transplant immune recovery to reduce both infectious complications and disease recurrence. Preclinical studies implicate the naive T-cell subset as the primary driver of graft-versus-host disease (GvHD). In this phase I dose escalation study, we assessed the safety of a DLI that was depleted of CD45RA+ naive T cells. Sixteen adult patients received a prophylactic DLI at a median of 113 days (range 76-280 days) following an HLA-identical, non-myeloablative allogeneic hematopoietic stem cell transplantation. Three patients each received the naive T-cell depleted DLI with a CD3+ dose of 1 × 105/kg, 1 × 106/kg, and 5 × 106/kg. The maximum dose of 1 × 107/kg was expanded to 7 patients. No dose-limiting grade III/IV acute GvHD or adverse events attributable to the DLI were observed at any dose level. One patient developed grade 2 acute GvHD of skin and upper intestines, and another developed moderate chronic GvHD of the lungs following the DLI. With a median follow-up of 2.8 years, 2-year progression-free and overall survival is 50.0% and 68.8%, respectively. In conclusion, these data suggest that a DLI that has been depleted of CD45RA+ naive T cells is feasible and carries a low risk of acute or chronic GvHD.
Authors
Maung, KK; Chen, BJ; Barak, I; Li, Z; Rizzieri, DA; Gasparetto, C; Sullivan, KM; Long, GD; Engemann, AM; Waters-Pick, B; Nichols, KR; Lopez, R; Kang, Y; Sarantopoulos, S; Sung, AD; Chao, NJ; Horwitz, ME
MLA Citation
Maung, Ko K., et al. “Phase I dose escalation study of naive T-cell depleted donor lymphocyte infusion following allogeneic stem cell transplantation.Bone Marrow Transplant, July 2020. Pubmed, doi:10.1038/s41409-020-0991-5.
URI
https://scholars.duke.edu/individual/pub1450672
PMID
32624583
Source
pubmed
Published In
Bone Marrow Transplant
Published Date
DOI
10.1038/s41409-020-0991-5

The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD.

Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant patients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immunomodulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.
Authors
Markey, KA; Schluter, J; Gomes, ALC; Littmann, ER; Pickard, AJ; Taylor, BP; Giardina, PA; Weber, D; Dai, A; Docampo, MD; Armijo, GK; Slingerland, AE; Slingerland, JB; Nichols, KB; Brereton, DG; Clurman, AG; Ramos, RJ; Rao, A; Bush, A; Bohannon, L; Covington, M; Lew, MV; Rizzieri, DA; Chao, N; Maloy, M; Cho, C; Politikos, I; Giralt, S; Taur, Y; Pamer, EG; Holler, E; Perales, M-A; Ponce, DM; Devlin, SM; Xavier, J; Sung, AD; Peled, JU; Cross, JR; van den Brink, MRM
MLA Citation
Markey, Kate A., et al. “The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD.Blood, vol. 136, no. 1, July 2020, pp. 130–36. Pubmed, doi:10.1182/blood.2019003369.
URI
https://scholars.duke.edu/individual/pub1441380
PMID
32430495
Source
pubmed
Published In
Blood
Volume
136
Published Date
Start Page
130
End Page
136
DOI
10.1182/blood.2019003369

Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant.

Importance: Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known. Objective: To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT. Design, Setting, and Participants: This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020. Interventions: Patients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89). Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD). Results: Of 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen. Conclusions and Relevance: The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.
Authors
Ghosh, N; Ahmed, S; Ahn, KW; Khanal, M; Litovich, C; Aljurf, M; Bacher, VU; Bredeson, C; Epperla, N; Farhadfar, N; Freytes, CO; Ganguly, S; Haverkos, B; Inwards, D; Kamble, RT; Lazarus, HM; Lekakis, L; Murthy, HS; Nishihori, T; Ramakrishnan, P; Rizzieri, DA; Yared, JA; Kharfan-Dabaja, MA; Sureda, A; Hamadani, M
MLA Citation
URI
https://scholars.duke.edu/individual/pub1446967
PMID
32496525
Source
pubmed
Published In
Jama Oncol
Published Date
DOI
10.1001/jamaoncol.2020.1278