Magrolimab + azacitidine versus azacitidine + placebo in untreated higher risk (HR) myelodysplastic syndrome (MDS): The phase 3, randomized, ENHANCE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7055-TPS7055
Author(s):  
Guillermo Garcia-Manero ◽  
Naval Guastad Daver ◽  
Jin Xu ◽  
Mark Chao ◽  
Trisha Chung ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Tumor Cells ◽  
Immune Cell ◽  
Residual Disease ◽  
Unmet Need ◽  
International Prognostic Scoring System ◽  
Phase 3 ◽  
Patient Reported ◽  
Very High

TPS7055 Background: MDS is a clonal myeloid disorder characterized by cytopenia and ineffective hematopoiesis. The median age of diagnosis is approximately 70 yrs of age and prognosis and treatment are guided by the Revised International Prognostic Scoring System (IPSS-R) criteria. Patients with intermediate, high and very high risk MDS (HR-MDS) have a median overall survival (OS) of 0.8 to 3.7 years. Despite the high unmet need in this patient population, azacitidine (AZA) is the only approved therapy for HR-MDS which has improved overall survival in clinical trials to date. However, these agents lead to low complete response (CR) rates (10-17%) with limited OS ( = 2 years), indicating a need for alternative therapy. Magrolimab is a first-in-class monoclonal antibody that blocks the macrophage inhibitory immune checkpoint CD47, a “do not eat me” signal overexpressed on tumor cells. Binding of magrolimab to CD47 leads to phagocytosis of tumor cells. AZA increases expression of prophagocytic “eat me” signals, facilitating synergy with magrolimab. In an ongoing phase 1b study, the combination of magrolimab + AZA led to high response rates (ORR 91%, with a CR of 42%) and an acceptable safety profile without significant immune-related adverse events. ENHANCE (NCT04313881) is a phase 3 trial comparing the efficacy and safety of magrolimab + AZA with that of AZA + placebo (PBO) in previously untreated patients with HR-MDS. Methods: Patients ≥18 years old with previously untreated intermediate to very high risk MDS by IPSS-R are eligible for ENHANCE. Randomization is 1:1 to magrolimab + AZA or AZA + PBO with no crossover allowed. Magrolimab or placebo is administered intravenously (IV) with an initial 1 mg/kg priming dose to mitigate on target anemia. An intrapatient dose escalation regimen up to 30 mg/kg is then administered through Cycle 1, 30 mg/kg weekly dosing in Cycle 2, with 30 mg/kg Q2W dosing occurring in Cycle 3 and beyond. AZA is administered per regional prescribing information. Patients may remain on treatment until disease progression, relapse, loss of clinical benefit, or until unacceptable toxicities occur. Two primary efficacy endpoints are CR rate and OS. For patients undergoing allogeneic stem cell transplantation (ASCT), data for the CR rate will be censored at the time of ASCT and OS will be censored at the last known alive date. Secondary efficacy endpoints include RBC transfusion independence rate, event-free survival, minimal residual disease-negative rate, time to AML transformation, and patient-reported Functional Assessment of Cancer Therapy (FACT)-Anemia response rate. Biomarkers of immune cell recruitment, immune cell signaling, and bone marrow penetration of magrolimab will also be explored. Planned enrollment is approximately 520 patients globally, which began in September 2020. Accrual is ongoing. Clinical trial information: NCT04313881.

First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma (MIUC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 391-391
Author(s):  
Dean F. Bajorin ◽  
Johannes Alfred Witjes ◽  
Jürgen Gschwend ◽  
Michael Schenker ◽  
Begoña P. Valderrama ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Radical Surgery ◽  
Unmet Need ◽  
Disease Free Survival ◽  
Phase 3 ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Disease Free

391 Background: The standard of care (SOC) for patients (pts) with MIUC is radical surgery ± cisplatin-based neoadjuvant chemotherapy (chemo), but many pts are cisplatin-ineligible. There is no conclusive evidence supporting adjuvant chemo in pts who did not receive neoadjuvant chemo and in those with residual disease after neoadjuvant cisplatin. This phase 3 trial of adjuvant nivolumab (NIVO) vs placebo (PBO) in pts with MIUC after radical surgery ± neoadjuvant cisplatin (CheckMate 274) aims to address an unmet need in these pts. We report the initial results. Methods: This is a phase 3, randomized, double-blind, multicenter trial of NIVO vs PBO in pts with high-risk MIUC (bladder, ureter, or renal pelvis) after radical surgery. Pts were randomized 1:1 to NIVO 240 mg Q2W or PBO for ≤ 1 year of adjuvant treatment. Pts had radical surgery within 120 days ± neoadjuvant cisplatin or were ineligible/declined cisplatin-based chemo, evidence of UC at high risk of recurrence per pathologic staging, were disease-free by imaging, and ECOG PS ≤ 1. Primary endpoints: disease-free survival (DFS) in all randomized pts (ITT population) and in pts with tumor PD-L1 expression ≥ 1%. DFS was stratified by nodal status, prior neoadjuvant cisplatin, and PD-L1 status. Non–urothelial tract recurrence-free survival (NUTRFS) in ITT pts and in pts with PD-L ≥ 1% is a secondary endpoint. Safety is an exploratory endpoint. Results: In total, 353 pts were randomized to NIVO (PD-L1 ≥ 1%, n = 140) and 356 pts to PBO (PD-L1 ≥ 1%, n = 142). The primary endpoint of DFS was met in ITT pts (median follow-up, 20.9 mo for NIVO; 19.5 mo for PBO) and in pts with PD-L1 ≥ 1%. DFS and NUTRFS were improved with NIVO vs PBO in both populations (Table). DFS improvement with NIVO was generally consistent across subgroups. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 17.9% and 7.2% of pts in the NIVO and PBO arms, respectively. Conclusions: NIVO demonstrated a statistically significant and clinically meaningful improvement in DFS vs PBO for MIUC after radical surgery, both in ITT pts and pts with PD-L1 ≥ 1%. AEs were manageable and consistent with previous reports. These results support adjuvant NIVO as a new SOC for pts with MIUC with high risk for recurrence despite neoadjuvant chemo or those ineligible for and/or declining cisplatin-based chemo. Clinical trial information: NCT02632409 . Research Sponsor: Bristol Myers Squibb[Table: see text]

scholarly journals MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen

2019 ◽  
Vol 3 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Haris Ali ◽  
Ibrahim Aldoss ◽  
Dongyun Yang ◽  
Sally Mokhtari ◽  
Samer Khaled ◽  
...  
Keyword(s):  
Molecular Markers ◽  
High Risk ◽  
Scoring System ◽  
Conditioning Regimen ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Transplantation Outcomes ◽  
Very High

Abstract Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.

scholarly journals GOOD OUTCOME FOR VERY HIGH RISK ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA CARRYING GENETIC ABNORMALITIES t(4;11)(q21;q23) or t(9;22)(q34;q11), IF PROMPTLY SUBMITTED TO ALLOGENEIC TRANSPLANTATION, AFTER OBTAINING A GOOD MOLECULAR REMISSION.

2015 ◽  
Vol 7 ◽  
pp. e2015041 ◽  
Author(s):  
Matteo Parma ◽  
Clara Vigano' ◽  
Monica Fumagalli ◽  
Federica Colnaghi ◽  
Arianna Colombo ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Residual Disease ◽  
Immunosuppressive Drugs ◽  
Favourable Outcome ◽  
Molecular Remission ◽  
Hematopoietic Stem ◽  
Genetic Abnormalities ◽  
Very High

Background and Objectives: Acute lymphoblastic leukaemia (ALL) carrying t(9;22) or t(4;11) genetic abnormalities represents a very high risk subtype of disease (VHR-ALL). Hematopoietic stem cell transplantation (HSCT) still remains the only curative option also in the Imatinib era. In the last years low molecular level of minimal residual disease (MRD) before HSCT was reported as one of the best favourable indexes for survival in ALL. Here we observed that even these patients can show a favourable outcome, if submitted to HSCT with very low MRD. Methods: We considered 18 consecutive VHR-ALL patients eligible to HSCT. 16 of them were transplanted upon first remission, as soon as possible, employing myelo-ablative conditioning regimens. Molecular MRD has been evaluated before and after HSCT.Results: Immediately before HSCT MRD revealed: complete molecular remission (MRDneg) for 5 patients and a level <1x10-3 for 7 patients; 100 days after HSCT we had: MRDneg for 7 patients and a decrease for all the others after HSCT. After tapering of immunosuppressive drugs, 13 patients reached the MRDneg in a median time of 8 months (range 3-16); Based on intention to treat analysis: 14/18 patients are alive and disease free at the time of analysis, overall survival and event free survival is of 78% and 66% respectively, with an average follow-up of 45 months (range 6-84) since HSCT. Conclusion: Early transplantation with low MRD level seems to be correlated with a favourable outcome also in VHR-ALL

Minimal Residual Disease in Gastric Cancer: Evidence of an Independent Prognostic Relevance of Urokinase Receptor Expression by Disseminated Tumor Cells in the Bone Marrow

2002 ◽  
Vol 20 (8) ◽  
pp. 2005-2016 ◽  
Author(s):  
Markus Maria Heiss ◽  
Erich H. Simon ◽  
Bianca C.M. Beyer ◽  
Klaus Uwe Gruetzner ◽  
Anwar Tarabichi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Tumor Cells ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Disseminated Tumor Cells ◽  
Primary Surgery ◽  
Disease Free ◽  
Minimal Residual

PURPOSE: To study the invasion-related molecule urokinase-type plasminogen activator receptor (u-PAR) expressed by disseminated tumor cells as a biologic predictor of poor survival in a large prospective series of patients with gastric cancer. PATIENTS AND METHODS: In 156 gastric cancer patients (prospective series), disseminated tumor cells in the bone marrow and the u-PAR expressed by these tumor cells were determined by cytokeratin (CK) 18 immunocytochemistry and u-PAR/CK18 double immunocytochemistry. RESULTS: In contrast to the mere detection of disseminated tumor cells at primary surgery, the additional evidence of u-PAR on these cells correlated significantly with pathologic T stage (P = .0474) and the expression of u-PAR (P = .0093) and plasminogen-activator inhibitor 1 (P = .0145) in the primary tumor (immunohistochemistry, χ2). Kaplan-Meier analysis revealed no association with prognosis for the mere detection of disseminated tumor cells. In contrast, a significant association was seen between detection of u-PAR on these cells and shorter disease-free (P < .0001) and overall survival (P < .0001). Multivariate analysis revealed that u-PAR on disseminated tumor cells at the time of primary surgery is an independent prognostic factor for disease-free (95% confidence interval [CI], 1.72 to 3.21; P = .024) and overall survival (P = .0049; relative risk, 2.89; 95% CI, 1.92 to 4.30). CONCLUSION: This is the first large study to show that u-PAR, detected on disseminated tumor cells in the bone marrow, is an independent prognostic parameter in gastric cancer, in contrast to the mere detection of minimal residual disease (MRD). u-PAR may be a promising marker to define a critical subpopulation of disseminated tumor cells and a target to eliminate MRD. Molecular phenotyping of MRD is critical for defining its individual clinical relevance.

Prognostic Impact of Different High Risk Features in Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in First Complete Remission.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2303-2303
Author(s):  
Theis Terwey ◽  
Philipp Hemmati ◽  
Gero Massenkeil ◽  
Bernd Dörken ◽  
Renate Arnold
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Prognostic Impact ◽  
Very High ◽  
First Complete Remission

Abstract Abstract 2303 Poster Board II-280 Introduction: In acute lymphoblastic leukemia (ALL) specific clinical and biological features confer high relapse risk and inferior overall survival (OS) after treatment with conventional chemotherapy alone. The differential prognostic impact of these high risk features after treatment with allogeneic hematopoietic stem cell transplantation (HCT) has not been well studied. Patients and Methods: 79 adult ALL patients in first complete remission (CR) received allogeneic HCT at our center between 1995 and 2008. All patients were high or very high risk according to German Multicenter Study Group for Adult ALL (GMALL) criteria. Median age was 36 years (range: 17-68). Patients received high-dose conditioning consisting of 12 Gy total body irradiation ± etoposide ± cyclophosphamide (n=69, 87%) or reduced intensity conditioning (RIC) consisting of fludarabine/busulfan/ATG (n=10, 13%) and HSCT from related (n=34, 43%) or unrelated (n=45, 57%) donors. Bone marrow (n=17, 22%) or peripheral blood stem cells (n=62, 78%) were given. Graft-versus-host-disease prophylaxis was CSA/MTX for high-dose conditioning or CSA/MMF for RIC. Results: Patients were classified as high risk or very high risk due to Philadelphia chromosome-positive disease (Ph+) (n=30, 38%), leukocytosis>30/nl at diagnosis in B-ALL (n=25, 23%), late response to induction therapy in B-ALL (>week 4) (n=13, 16%), early or mature T-ALL (n=13, 16%), pro-B-ALL/t(4;11) (n=8, 10%), persistence of minimal residual disease (MRD) (>week 16) (n=8, 10%) or complex aberrant karyotype (n=6, 8%). 57 patients (72%) presented with one high risk feature, whereas 20 patients (25%) and 2 patients (3%) presented with two or three features, respectively. Currently, after a median follow-up of 56 months (7-169) 49 patients (62%) remain alive. Projected OS of the whole cohort at 1, 2 and 5 years was 78%, 70% and 55% and leukemia-free survival was 77%, 66% and 55%. Cumulative incidence of non-relapse mortality (NRM) and relapse mortality (RM) at 5 years was 23% and 18%, respectively. In multivariate Cox regression analysis, a non-significant trend for inferior OS was seen for patients with early or mature T-ALL (hazard ratio (HR): 2.03 (95%CI: 0.92-4.52), p=0.082), whereas no differential effect on OS, NRM or RM was seen for any other high risk feature (Table 1). In additional analyses, inferior OS (HR 1.81 (95%CI: 1.02-3.29), p=0.043) and increased RM (HR 2.17 (95%CI 1.16-4.05), p=0.015) was observed for patients with more than one high risk feature. Conclusions: In summary, this single center study on allogeneic HCT in high risk ALL found a negative prognostic trend for early or mature T cell immunophenotype. No differential prognostic impact on OS, NRM and RM was seen for other high risk features as defined by GMALL criteria, however this conclusion is limited by the low patient number in some of the subgroups. Overall survival for the whole cohort was 55% at 5 years, with inferior OS and higher RM being observed in patients with more than one high risk feature. Disclosures: No relevant conflicts of interest to declare.

Disease Response Guiding Therapy in Acute Lymphocytic Leukemia: Pivotal Role of Minimal Residual Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-34-SCI-34
Author(s):  
Michael A. Pulsipher
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Lower Risk ◽  
Residual Disease ◽  
Response To Therapy ◽  
Risk Patients ◽  
Very High ◽  
Minimal Residual ◽  
Risk Of Relapse

In spite of an explosion of data regarding mutations associated with childhood ALL, to date these key genetic changes rarely have been the driver of therapy. Clinical parameters at presentation (WBC, age, T- vs. B-lineage, etc.) have dictated initial risk stratification and induction approaches, followed by risk-adapted therapy based upon leukemic response measured by minimal residual disease (MRD, either PCR- or flow cytometry-based). With minor variations, rapid disappearance of peripheral MRD, followed by significant clearance from the marrow after induction, and most importantly, the level of MRD after consolidation have allowed clear distinctions in outcomes that have driven intensification or de-intensification of therapy resulting in improved outcomes. Although specific gene mutations have been associated with risk, MRD has further identified better risk patients within genetic subgroups. For patients noted to be very high risk who are candidates for hematopoietic cell transplantation (HCT), the presence of MRD both pre- and post-transplant has been associated with increased risk of relapse; the risk being modified by level of MRD, whether or not GVHD occurs after HCT, and timing after HCT when MRD is measured. In lower risk patients being treated with chemotherapy and higher risk patients eligible for HCT, more sensitive approaches to flow cytometry and PCR, as well as next-generation sequencing (NGS) MRD approaches (sensitive to 1/10^7 cells) are currently being tested. It is not clear yet whether NGS-MRD offers substantial improvements in patients treated with chemotherapy, as broad-based testing is underway; the latest comparative outcomes will be presented. There is evidence of a striking improvement in our ability to define patients who will do very will after transplant (not relapse), and preliminary evidence that post-HCT NGS MRD testing is more sensitive that other methodologies in defining risk of relapse after transplant. As the latest information about the ability of different approaches to MRD is shown in this session, we will also present how response to therapy based upon MRD interacts with various genetic subtypes (Ph+ ALL, extreme hypodiploidy, etc.). Even in subclasses that are considered very high risk based solely upon genetics, measurement of MRD can define higher and lower risk groups. Going forward, as more and different types of patients are subcategorized and treated with targeted agents based upon specific mutations, it is likely MRD response will continue to be important in mapping intensity of approach and defining children at highest risk of relapse who might benefit from HCT or other cellular therapeutic approaches. Disclosures Pulsipher: Novartis: Membership on an entity's Board of Directors or advisory committees.

Development and validation of a prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) from the phase 3 prevail clinical trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5022-5022
Author(s):  
Andrew J. Armstrong ◽  
Ping Lin ◽  
Celestia S. Higano ◽  
Cora N. Sternberg ◽  
Guru Sonpavde ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Prognostic Factors ◽  
High Risk ◽  
Prognostic Model ◽  
Risk Groups ◽  
Multivariable Model ◽  
Training Set ◽  
Phase 3 ◽  
Testing Set

5022 Background: Prognostic models require updating to reflect contemporary medical practice. In a post hoc analysis of the phase 3 PREVAIL trial (enzalutamide vs placebo), we identified prognostic factors for overall survival (OS) in chemotherapy-naive men with mCRPC. Methods: Patients were randomly divided 2:1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined candidate prognostic factors (including treatment) were analyzed in a multivariable Cox model with stepwise procedures and in a penalized Cox proportional hazards model using the adaptive least absolute shrinkage and selection operator (LASSO) penalty (data cutoff June 1, 2014). A multivariable model predicting OS was developed using the training set; the predictive accuracy was assessed in the testing set using time-dependent area under the curve (tAUC). The testing set was stratified based on risk score tertiles (low, intermediate, high), and OS was analyzed using Kaplan-Meier methodology. Results: Demographics, disease characteristics, and OS were balanced between the training and testing sets; median OS was 32.7 months for both datasets. There were no enzalutamide treatment-prognostic factor interactions (predictors). The final multivariable model included 11 prognostic factors: prostate-specific antigen, treatment, hemoglobin, neutrophil-lymphocyte ratio, liver metastases, time from diagnosis to randomization, lactate dehydrogenase, ≥ 10 bone metastases, pain, albumin, and alkaline phosphatase. The tAUC was 0.74 in the testing set. Median (95% confidence interval [CI]) OS for the low-, intermediate-, and high-risk groups (testing set) were not yet reached (NYR) (NYR–NYR), 34.2 months (31.5–NYR), and 21.1 months (17.5–25.0). The hazard ratios (95% CI) for OS in the low- and intermediate-risk groups vs the high-risk group were 0.20 (0.14–0.29) and 0.40 (0.30–0.53), respectively. Conclusions: Our validated prognostic model incorporates factors routinely collected in chemotherapy-naive men with mCRPC treated with enzalutamide and identifies subsets of men with widely differing survival times. Clinical trial information: NCT01212991.

ZUMA-8: A phase 1/2 multicenter study evaluating KTE-X19 in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS7566-TPS7566 ◽  
Author(s):  
Ian Flinn ◽  
Michael Marris ◽  
William G. Wierda ◽  
Steven Coutre ◽  
John M. Pagel ◽  
...  
Keyword(s):  
High Risk ◽  
Multicenter Study ◽  
Residual Disease ◽  
Phase 1 ◽  
Objective Response ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Phase 2 ◽  
T Cell Therapy ◽  
Patient Reported

TPS7566 Background: Despite treatment advances, CLL is largely incurable. First-line targeted therapy with ibrutinib mostly produces durable remissions, but high-risk disease or many prior therapies increases relapse risk (Ghia P, et al. Haematologica. 2014). Relapse after ibrutinib is associated with a poor outcome (Maddocks KJ, et al. JAMA Oncol. 2015). Allogeneic stem cell transplantation potentially offers long-term remissions but has a high risk of morbidity/mortality (Shustik C, et al. Ann Hematol. 2017). Autologous T cells expressing a CD19-specific chimeric antigen receptor (CAR) with a CD28 costimulatory domain may be efficacious against CLL (Kochenderfer JN, et al. Blood. 2012). KTE-X19 is an autologous anti-CD19 CAR T cell therapy under investigation for R/R hematologic malignancies and may offer longer durable remissions with manageable safety in pts with R/R CLL. ZUMA-8 is a Phase 1/2 multicenter study for pts with R/R CLL. Methods: Adult pts must have R/R CLL with ≥ 2 prior treatment regimens, disease progression on ibrutinib, ECOG 0-1, and adequate organ function. Phase 1 will enroll 12-18 pts to assess dose-limiting toxicities (DLTs) with a 6 + 3 dose escalation/de-escalation design; 30 more pts may be enrolled to further assess safety. Phase 2 will enroll ≈60 pts to evaluate efficacy and safety. Pts will undergo leukapheresis followed by optional bridging therapy. Cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) conditioning chemotherapy will be given on Days -5, -4 and -3. KTE-X19 will be given on Day 0 at 0.5, 1 or 2 × 106 KTE-X19 cells/kg. The primary endpoint is incidence of DLTs for Phase 1 and independent review committee-assessed objective response rate (ORR) per iwCLL 2018 criteria for Phase 2. Secondary endpoints include complete remission (CR) rate, investigator-assessed ORR, minimal residual disease (MRD) negativity rate, MRD-negative CR rate, duration of response, progression-free survival, overall survival, safety, and patient-reported outcomes (Phase 2). Serum cytokine and blood KTE-X19 cell levels over time and level of anti-KTE-X19 antibodies are exploratory endpoints. Accrual is ongoing. Clinical trial information: NCT03624036.

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