PHASE I DOSE-ESCALATION STUDY OF VENETOCLAX PLUS BEAM FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) FOR CHEMORESISTANT, RELAPSED/REFRACTORY, OR HIGH-RISK NON-HODGKIN'S LYMPHOMA (NHL); PRELIMINARY RESULTS

2019 ◽  
Vol 37 ◽  
pp. 528-529
Author(s):  
J. Maakaron ◽  
Q. Zhao ◽  
M. Puto ◽  
R. Von Derau ◽  
J. Robinson ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Phase I ◽  
Dose Escalation ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Hodgkin's Lymphoma ◽  
Cell Transplant ◽  
Dose Escalation Study ◽  
Preliminary Results

Dasatinib (SPRYCEL®) in Children and Adolescents with Relapsed or Refractory Leukemia: Preliminary Results of the CA180018 Phase I/II Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2162-2162 ◽  
Author(s):  
Christian M. Zwaan ◽  
M.L. den Boer ◽  
B. Beverloo ◽  
V. van der Velden ◽  
A. Countouriotis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase I ◽  
Dose Escalation ◽  
Pediatric Patients ◽  
Stem Cell Transplant ◽  
Patient Dose ◽  
Cell Transplant ◽  
Molecular Responses ◽  
Preliminary Results ◽  
Prior Therapy

Abstract Leukemia is the most common type of cancer in pediatric patients (pts). Treatment options for Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) include: risk-adapted chemotherapy, imatinib (im) and stem cell transplant (SCT). Relapsed leukemia has few therapeutic options. Dasatinib (SPRYCEL®, formerly BMS-354825) is a novel, oral, multi-targeted kinase inhibitor of BCR-ABL, KIT, and SRC kinases that was recently granted approval for adults with CML, and Ph+ ALL with resistance or intolerance to prior therapy. CA180018 is the first trial evaluating dasatinib in pediatric patients pts and Ph+ and in Ph- leukemias. CA180018 is a phase I/II dose-finding study of dasatinib in pts aged 1–20 with CML or relapsed Ph+ ALL resistant or intolerant to im, or Ph- ALL or AML in ≥2nd relapse performed in collaboration with 12 centers (6 countries) from the ITCC Consortium. Preliminary data are available on the first 15 pts treated from March-July 2006 (2 chronic phase (CP) CML, 7 Ph+ ALL, 1 accelerated phase (AP) CML, 3 Ph- ALL, and 2 Ph- AML) at a starting dose of 60 mg/m2 daily (course = 3 weeks). Intra-patient dose escalation was allowed for lack of initial response, and a 3+3 design for maximum tolerated dose (MTD) determination. Hematologic, cytogenetic, and molecular responses, as well as plasma and cerebrospinal fluid (CSF) pharmacokinetic (PK) analysis and BCR-ABL mutational analysis are ongoing. Median age was 11 yrs (range 4–17), median time from diagnosis of leukemia was 19.5 months (range 1.4–89.9). Prior therapy included chemotherapy, im, and stem cell transplant. Median duration on study is 0.69 month (range 0.03–3.45). Intra-patient dose escalation to 80 or 100 mg/m2 occurred in 7 pts. Six pts remain on study. There have been 7 responders: 4 complete hematologic responses (CHR): 1 CP CML, 1 AP CML, 2 Ph+ ALL; 5 cytogenetic responses (CyR): 2 Ph+ ALL complete CyR (CCyR), 1 AP CML CCyR, 1 CP CML partial CyR (PCyR), 1 Ph+ ALL minor CyR who never achieved a CHR, and then progressed; and 2 Ph+ ALL pts with CNS disease who cleared the CSF of leukemic blasts with single agent dasatinib. Preliminary PK in 7 pts showed rapid absorption with a median Tmax of 1.0 h, and mean terminal phase half-life (SD) of 2.7 (1.1) h. There is one dose-limiting toxicity (DLT): grade 4 anaphylactic shock which occurred 5 hours after the first dose. Dasatinib has otherwise been well tolerated up to 100 mg/m2 with toxicities including grade 3/4 thrombocytopenia, and sepsis. Nine pts are off study: 8 for progressive disease (2 Ph+ ALL pts with a resistant T315I BCR-ABL mutation), and 1 DLT. These preliminary results provide evidence supporting the safety and efficacy of dasatinib in pediatric pts with relapsed or refractory leukemia. An updated analysis including further enrollment, safety data, PK, cytogenetic and molecular responses, and mutational analyses will be presented.

A phase I trial of lenalidomide maintenance after autologous stem cell transplant (ASCT) in patients with high-risk relapsed/refractory lymphomas.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8553-8553
Author(s):  
Jakub Svoboda ◽  
Lauren Strelec ◽  
Nirav Niranjan Shah ◽  
Elise A Chong ◽  
Kathleen Montrey ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Phase I ◽  
Phase I Trial ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

scholarly journals Lenalidomide Maintenance after Autologous Stem Cell Transplant in Patients with High-Risk Relapsed/Refractory Lymphomas Is Feasible and Compares Favorably to Historical Controls: Results of a Phase I/II Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4639-4639 ◽  
Author(s):  
Jakub Svoboda ◽  
Lauren E. Strelec ◽  
Daniel J. Landsburg ◽  
Sunita Dwivedy Nasta ◽  
Anthony R. Mato ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Grade 3 ◽  
Historical Controls

Abstract Background: Lymphoma patients with residual hypermetabolic lesions on FDG-PET imaging after salvage chemotherapy have poor outcomes following autologous stem cell transplant (ASCT). We have previously shown progression free survival (PFS) of only 5 months (range: 1-19) in this population with only 7% of patients without progression at 12 months (Svoboda et al, BMT 2006). We hypothesized that these high-risk patients may benefit from continued therapy after ASCT. Lenalidomide is an immunomodulatory agent which has been used as maintenance in other hematologic malignancies, but its toxicity and efficacy have not been well described in lymphoma patients following ASCT. Methods: We are conducting a phase I/II prospective, open-label trial of lenalidomide maintenance after ASCT in lymphoma patients at high risk for relapse defined by residual FDG-PET positive lesions (SUV ≥ 2.5) immediately prior to ASCT. The primary objective of phase I was to determine the safety and dose-limiting toxicity (DLT) of lenalidomide maintenance. A 3+3 de-escalation design was used with a starting dose of lenalidomide at 10 mg on days 1 through 28 of each 28-day cycle. Lenalidomide was initiated 28-100 days post-ASCT and planned for up to 24 cycles. DLT was defined as non-hematologic toxicity ≥ grade 3 or hematologic toxicity ≥ grade 4 during the first 28 days of lenalidomide. The primary objectives of phase II were PFS and overall survival (OS). Survival outcomes were calculated from the date of ASCT. Enrollment began in 5/2012; we report data through 7/2016. Results: Fourteen patients were enrolled and 11 were evaluable (one patient withdrew consent and two progressed prior to initiation of lenalidomide). Eight (73%) evaluable patients had diffuse large B-cell lymphoma (DLBCL): 4 with germinal center (GC) origin and 4 non-GC by Hans algorithm. Three (27%) patients had Hodgkin lymphoma. Median age was 44 years (29-61), ECOG PS 0 (0- 1), prior therapies 2 (2-5). Median follow-up was 24 months (range 8-44), and median time on lenalidomide was 13 cycles (1-24). No DLTs were observed in phase I, and the dose of 10 mg daily was determined to be appropriate for phase II. Six (55%) patients discontinued lenalidomide: 3 due to disease progression, 2 at investigator's discretion (1 subsequently progressed), and 1 due to grade 3 rash possibly related to lenalidomide. Of 3 patients who discontinued lenalidomide due to progression, 1 (non-GC DLBCL) died of disease progression, 1 (GC DLBCL) achieved complete remission (CR) with allotransplant, and 1 (non-GC DLBCL) remains on another active therapy. Overall, 8 (73%) patients remain in CR following ASCT, including 3 patients who discontinued lenalidomide. Of note, 1 patient developed adenocarcinoma of the colon 1 year after completion of lenalidomide, and 1 patient developed therapy-related acute myeloid leukemia at 10 months after discontinuing lenalidomide. At a median follow-up of 24 months, PFS of the complete cohort was 62.3% (95% CI: 0.28-0.84; Figure 1) and median PFS was not reached. OS was 75% (95% CI: 0.30-0.93; Figure 2) and median OS was not reached. When compared to the reported PFS of 7% at 12 months in the historical controls with identical high risk pre-transplant characteristics, the PFS of 62.3% (95% CI: 0.28-0.84) at 12 months was significantly improved (Z-test, p<0.05). Conclusion: We established feasibility of lenalidomide maintenance at 10 mg daily after ASCT in patients with relapsed/refractory lymphomas. Preliminary clinical outcomes observed in this phase I/II trial are very encouraging when compared to historical controls. To better understand the toxicity profile and validate the promising clinical benefit, the strategy of utilizing immunomodulatory agents as post-transplant maintenance should be studied in a larger cohort of high-risk lymphoma patients. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Svoboda: Pharmacyclics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding. Nasta:Millennium Pharmaceuticals: Research Funding. Mato:Abbvie: Research Funding; Acerta Pharma: Research Funding; Gilead Sciences: Research Funding; ProNAi: Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Consultancy; Theradex: Research Funding; TG Therapeutics: Research Funding; Gilead Sciences: Consultancy; Abbvie: Consultancy. Hwang:Novartis: Research Funding. Schuster:Janssen Research & Development: Research Funding; Gilead: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Research Funding; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria; Hoffman-LaRoche: Research Funding; Merck: Research Funding.

Factors Impacting Time to Engraftment in Patients With High-risk Neuroblastoma Following Autologous Stem Cell Transplant

2020 ◽  
Vol 42 (7) ◽  
pp. e569-e574
Author(s):  
Kirsty Hillier ◽  
W. Susan Cheng ◽  
Sarah B. Whittle ◽  
Robert Krance ◽  
Jennifer H. Foster
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant
Sign in / Sign up

Export Citation Format

Share Document