Cristina Gasparetto

Overview:

Dr. Gasparetto performs both laboratory and clinical research in the field of multiple myeloma. Her primary research interests are in developing immunotherapy approaches to treating multiple myeloma particularly in conjunction with hematopoietic stem cell transplantation. Ongoing laboratory research projects include the development of dendritic cell vaccines and antibody therapies. Clinical studies include a recently approved trial involving vaccination with autologous dendritic cells pulsed with idiotypic protein following high dose chemotherapy and autologous peripheral blood stem cells transplant. Upcoming trials include novel antibody therapies for multiple myeloma. Dr. Gasparetto is also an investigator on several other clinical trials for myeloma including non-myeloablative allogeneic transplantation, high dose sequential chemotherapy and autologous peripheral blood stem cell transplantation and transplantation of partially HLA matched unrelated cord blood.

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. 1986

Sapienza University of Rome (Italy)

Medical Resident, Medicine

Duke University

Fellow in Hematology/Oncology, Medicine

Duke University

Grants:

Dendritic Cell Based Vaccination for Multiple Myeloma

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

A Phase 2, Open-label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination with Pomalidomide and Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma

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

A Phase 1/2, Multicenter, Dose-Escalation and Expansion Study of Combination Therapy with Venetoclax, Daratumumab and Dexamethasone (with and without Bortezomib) in Subjects with Relapsed or Refractory Multiple Myeloma

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

Open-Label, Multicenter, Dose-Escalation Expansion Phase IB study to Evaluate Safety, Pharmacokinetics, and activity of BET Inhibitor RO6870810, Given as Mono- and combination Therapy to patients with Advanced Multiple Myeloma

Administered By
Duke Cancer Institute
Awarded By
F. Hoffmann-La Roche Ltd
Role
Principal Investigator
Start Date
End Date

A Phase 1, Open Label Study to evaluate the safety Pharmacokinetic, Pharmacodynamic and clinical activity of PF-06863135, A B-Cell Maturation Antigen (BCMA)- CD3 Bispecifi Antibody In Patient

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

Publications:

Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma.

Multiple myeloma (MM) remains an incurable disease and there is an unmet medical need for novel therapeutic drugs that do not share similar mechanisms of action with currently available agents. Sphingosine kinase 2 (SK2) is an innovative molecular target for anticancer therapy. We previously reported that treatment with SK2 inhibitor opaganib inhibited myeloma tumor growth in vitro and in vivo in a mouse xenograft model. In the current study, we performed a phase I study of opaganib in patients with relapsed/refractory multiple myeloma (RRMM). Thirteen patients with RRMM previously treated with immunomodulatory agents and proteasome inhibitors were enrolled and treated with single-agent opaganib at three oral dosing regimens (250 mg BID, 500 mg BID, or 750 mg BID, 28 days as a cycle). Safety and maximal tolerated dose (MTD) were determined. Pharmacokinetics, pharmacodynamics, and correlative studies were also performed. Opaganib was well tolerated up to a dose of 750 mg BID. The most common possibly related adverse event (AE) was decreased neutrophil counts. There were no serious AEs considered to be related to opaganib. MTD was determined as at least 750 mg BID. On an intent-to-treat basis, one patient (7.7%) in the 500 mg BID dose cohort showed a very good partial response, and one other patient (7.7%) achieved stable disease for 3 months. SK2 is an innovative molecular target for antimyeloma therapy. The first-in-class SK2 inhibitor opaganib is generally safe for administration to RRMM patients, and has potential therapeutic activity in these patients. Clinicaltrials.gov: NCT02757326.
Authors
Kang, Y; Sundaramoorthy, P; Gasparetto, C; Feinberg, D; Fan, S; Long, G; Sellars, E; Garrett, A; Tuchman, SA; Reeves, BN; Li, Z; Liu, B; Ogretmen, B; Maines, L; Ben-Yair, VK; Smith, C; Plasse, T
MLA Citation
Kang, Yubin, et al. “Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma.Ann Hematol, Dec. 2022. Pubmed, doi:10.1007/s00277-022-05056-7.
URI
https://scholars.duke.edu/individual/pub1558756
PMID
36460794
Source
pubmed
Published In
Ann Hematol
Published Date
DOI
10.1007/s00277-022-05056-7

Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology.

Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections. The NCCN Multiple Myeloma Panel members have developed guidelines for the management of patients with various plasma cell dyscrasias, including solitary plasmacytoma, smoldering myeloma, multiple myeloma, systemic light chain amyloidosis, and Waldenström's macroglobulinemia. The recommendations specific to the diagnosis and treatment of patients with newly diagnosed MM are discussed in this article.
Authors
Kumar, SK; Callander, NS; Alsina, M; Atanackovic, D; Biermann, JS; Chandler, JC; Costello, C; Faiman, M; Fung, HC; Gasparetto, C; Godby, K; Hofmeister, C; Holmberg, L; Holstein, S; Huff, CA; Kassim, A; Liedtke, M; Martin, T; Omel, J; Raje, N; Reu, FJ; Singhal, S; Somlo, G; Stockerl-Goldstein, K; Treon, SP; Weber, D; Yahalom, J; Shead, DA; Kumar, R
MLA Citation
Kumar, Shaji K., et al. “Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology.J Natl Compr Canc Netw, vol. 15, no. 2, Feb. 2017, pp. 230–69. Pubmed, doi:10.6004/jnccn.2017.0023.
URI
https://scholars.duke.edu/individual/pub1244347
PMID
28188192
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
15
Published Date
Start Page
230
End Page
269
DOI
10.6004/jnccn.2017.0023

448 Lemzoparlimab (TJ011133), an anti-CD47 antibody, with/without dexamethasone plus anti-myeloma regimens for relapsed/refractory multiple myeloma: a phase 1b dose escalation and expansion study

<jats:sec><jats:title>Background</jats:title><jats:p>Despite therapeutic advancements for multiple myeloma (MM), most patients with MM develop relapsed/refractory (R/R) disease, which is associated with high mortality and highlights an unmet need for novel treatments.A key characteristic of MM cells is the overexpression of CD47, which downregulates phagocytosis, thereby allowing malignant plasma cells to evade destruction by the immune system. Blocking CD47 with lemzoparlimab, an anti-CD47 monoclonal antibody, may enhance macrophage-mediated anti-tumor activity.This study will characterize the safety, dose-limiting toxicity, and recommended dosing of lemzoparlimab (TJ011133) with or without dexamethasone and combined with other anti-myeloma regimens in patients with R/R MM.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This phase 1b, open-label, dose-escalation and expansion study (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04895410">NCT04895410</jats:ext-link>) will enroll adults with R/R MM, an Eastern Cooperative Oncology Group Performance Status ≤2, prior treatment history (varies based on treatment arm; Figure 1), and measurable disease (serum monoclonal paraprotein [M-protein] ≥0.5 g/dL, urine M-protein ≥200 mg/24 hours, or serum-free light chain ≥100 mg/L).Patients will be enrolled in 2 phases (escalation and expansion), divided into 4 arms to receive treatment in 28-day cycles (figure 1): (A) lemzoparlimab ± dexamethasone; (B) lemzoparlimab + dexamethasone + pomalidomide (4 mg orally daily [Days 1–21]); (C) lemzoparlimab + dexamethasone + carfilzomib (56 mg/m2 intravenously, 6 doses/cycle [first 2 doses in Cycle 1: 20 mg/m2]); and (D) lemzoparlimab + dexamethasone + daratumumab (1800 mg subcutaneously [Cycle 1, start on Day 2; Cycles 1–2, once weekly; Cycles 3–6, every 2 weeks; Cycles ≥7, Day 1]). Dexamethasone will be administered orally twice weekly at 20 mg for Arm C, and orally or intravenously weekly at 40 mg for other arms. Dose escalation will follow Bayesian optimal interval design. Once maximum tolerated dose/recommended phase 2 dose (RP2D) is determined, patients will be enrolled in the expansion. Treatment discontinuation criteria are: unacceptable toxicity, disease progression, consent withdrawal, or investigator’s discretion.The primary endpoint is determination of the RP2D. Secondary endpoints include safety and efficacy measures. Time-to-event endpoints will be analyzed using the Kaplan–Meier method.</jats:p></jats:sec><jats:sec><jats:title>Acknowledgements</jats:title><jats:p>AbbVie is funding this study and participating in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.Medical writing support was provided by Marta Rossi, PhD, of Fishawack Communications Ltd, and funded by AbbVie.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.</jats:p><jats:p>gov: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04895410">NCT04895410</jats:ext-link></jats:p></jats:sec><jats:sec><jats:title>Ethics Approval</jats:title><jats:p>The protocol, informed consent form(s), recruitment materials, and all patient materials will be submitted to the Independent Ethics Committee/Institutional Review Board for review and approval.</jats:p><jats:fig id="F1" position="float" orientation="portrait"><jats:label>Abstract 448 Figure 1</jats:label><jats:caption><jats:p>Study schematic</jats:p></jats:caption><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ABS_448_F001" position="float" orientation="portrait" /></jats:fig><jats:p>The dose escalation phase will follow BOIN; it will start with lemzoparlimab (TJ011133) monotherapy at DL1 in Arm A. If DL1 is not tolerated as monotherapy or as combination therapy, DL −1 will be evaluated. Investigation of combination arms will start after evaluation of monotherapy.</jats:p><jats:p>Arms A, B, C and D will include patients with R/R MM after progressing on defined therapies and number of prior lines of therapy.</jats:p><jats:p>BOIN, Bayesian optimal interval; DL, dose level; MM, multiple myeloma; R/R, relapsed/refractory.</jats:p></jats:sec>
Authors
Stadtmauer, E; Karlin, L; Weisel, K; Gatt, ME; Kansagra, A; Monohan, G; Yee, A; Rockow-Magnone, S; Cordero, J; Hoffman, D; Bueno, O; Wu, K; Gasparetto, C
MLA Citation
Stadtmauer, Edward, et al. “448 Lemzoparlimab (TJ011133), an anti-CD47 antibody, with/without dexamethasone plus anti-myeloma regimens for relapsed/refractory multiple myeloma: a phase 1b dose escalation and expansion study.” Journal for Immunotherapy of Cancer, vol. 9, no. Suppl 2, BMJ, 2021, pp. A476–A476. Crossref, doi:10.1136/jitc-2021-sitc2021.448.
URI
https://scholars.duke.edu/individual/pub1517926
Source
crossref
Published In
Journal for Immunotherapy of Cancer
Volume
9
Published Date
Start Page
A476
End Page
A476
DOI
10.1136/jitc-2021-sitc2021.448

A phase 1b dose-escalation/expansion study of BET inhibitor RO6870810 in patients with advanced multiple myeloma.

Authors
Ramasamy, K; Nooka, A; Quach, H; Htut, M; Popat, R; Liedtke, M; Tuchman, SA; Laubach, J; Gasparetto, C; Chanan-Khan, A; Hertzberg, M; deMario, M; Nueesch, E; Chesne, E; Franjkovic, I; Lechner, K; Kornacker, M; Cho, HJ
MLA Citation
Ramasamy, Karthik, et al. “A phase 1b dose-escalation/expansion study of BET inhibitor RO6870810 in patients with advanced multiple myeloma.Blood Cancer J, vol. 11, no. 9, Sept. 2021, p. 149. Pubmed, doi:10.1038/s41408-021-00545-w.
URI
https://scholars.duke.edu/individual/pub1496577
PMID
34480019
Source
pubmed
Published In
Blood Cancer Journal
Volume
11
Published Date
Start Page
149
DOI
10.1038/s41408-021-00545-w

A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma

Authors
Shah, JJ; Stadtmauer, EA; Abonour, R; Cohen, AD; Bensinger, WI; Gasparetto, C; Kaufman, JL; Lentzsch, S; Vogl, DT; Orlowski, RZ; Kim, EL; McKinley, MB; Durie, BGM
URI
https://scholars.duke.edu/individual/pub938803
Source
wos
Published In
Blood
Volume
120
Published Date