R2-MTX With Lenalidomide Maintenance in Newly-diagnosed PCNSL：a Multicenter Phase Ib/II Stuty

2019 ◽  
Author(s):  
Keyword(s):  
Newly Diagnosed ◽  
Phase Ib ◽  
Multicenter Phase

First-MIND: A phase Ib, open-label, randomized study to assess safety of tafasitamab (tafa) or tafa + lenalidomide (LEN) in addition to R-CHOP in patients with newly diagnosed DLBCL.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7540-7540
Author(s):  
David Belada ◽  
Katerina Kopeckova ◽  
Juan Miguel Bergua ◽  
Marc André ◽  
Ernesto Perez Persona ◽  
...  
Keyword(s):  
Performance Status ◽  
Randomized Study ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Dose Intensity ◽  
Newly Diagnosed ◽  
Open Label ◽  
Bulky Disease ◽  
Phase Ib ◽  
Ecog Ps

7540 Background: Tafasitamab is a humanized, Fc-modified anti-CD19 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity and phagocytosis. It is FDA-approved with LEN for adult patients (pts) with relapsed/refractory (R/R) DLBCL ineligible for autologous stem cell transplantation. First-MIND (NCT04134936) is a Phase Ib, open-label, randomized study of tafa + R-CHOP or tafa + LEN + R-CHOP in newly diagnosed DLBCL. Methods: Eligible pts were ≥18 years, treatment-naïve, with histologically confirmed DLBCL not otherwise specified, international prognostic index (IPI) 2–5 and ECOG performance status (PS) 0–2. Pts with known double- or triple-hit and transformed lymphoma were excluded. Treatment (Tx) comprised six 21-day cycles of tafa (12 mg/kg IV, Day [D] 1, 8, 15) + R-CHOP (arm A) or tafa (12 mg/kg IV, D1, 8, 15) + LEN (25 mg orally, D1–10) + R-CHOP (arm B). G-CSF and VTE prophylaxis was mandatory. Primary objective is safety; secondary objectives are ORR, PET-CR rate at end of Tx, PFS, long-term safety, pharmacokinetics, immunogenicity. Results: From Dec 2019 to Aug 2020, 83 pts were screened in Europe and the US; 66 were randomized (33 per arm). Data cut-off for this analysis: 9 Dec 2020; study is ongoing. Median age was 64.5 years (range 20–86). Overall, 30% (20/66) of pts were ≥70 years and many had high-risk disease: IPI 2 29%, IPI 3 46%, IPI 4 26%. ECOG PS: 47% of pts were ECOG PS 0, 44% PS 1, 9% PS 2. Most pts had stage III/IV disease (92%); 46% had bulky disease. All pts experienced a treatment-emergent adverse event (TEAE). Grade ≥3 neutropenia and thrombocytopenia occurred in 54.5% and 12.1% (arm A) and 66.7% and 30.3% (arm B) of pts, respectively (Table). Serious TEAEs occurred in 42.4% (arm A) and 51.5% (arm B) of pts. There were three deaths, unrelated to tafa and/or LEN (sepsis, urosepsis, and COVID-19 pneumonia). R-CHOP dose intensity was maintained in both arms. Among 60 pts who completed tumor assessments after cycle 3, ORR was 89.7% (arm A) and 93.5% (arm B). Conclusions: These data suggest R-CHOP + tafa or tafa + LEN is tolerable in pts with Tx-naïve DLBCL and that R-CHOP dosing is not affected. Toxicities are similar to those expected with R-CHOP or R-CHOP + LEN. Updated safety and early efficacy data will be presented at the conference. Clinical trial information: NCT04134936. [Table: see text]

OC-0333 Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial

2021 ◽  
Vol 161 ◽  
pp. S246-S247
Author(s):  
A. Laprie ◽  
G. Noel ◽  
L. Chaltiel ◽  
G. Truc ◽  
M. Sunyach ◽  
...  
Keyword(s):  
Phase Iii ◽  
Newly Diagnosed ◽  
Dose Painting ◽  
Phase Iii Trial ◽  
Multicenter Phase ◽  
Newly Diagnosed Glioblastoma

scholarly journals Results of the Phase 1b Dose Escalation Study of OPB-111077, Decitabine, and Venetoclax for the Treatment of Newly Diagnosed or Relapsed/Refractory AML

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Lindsay Wilde ◽  
Ubaldo Martinez-Outschoorn ◽  
Neil Palmisiano ◽  
Gina Keiffer ◽  
Margaret Kasner
Keyword(s):  
Dose Escalation ◽  
Research Funding ◽  
Acid Metabolism ◽  
Pharmaceutical Research ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Otsuka Pharmaceutical ◽  
Refractory Aml

Background: The combination of a hypomethylating agent (HMA) and the Bcl-2 inhibitor venetoclax (VEN) has revolutionized the treatment of elderly patients with newly diagnosed acute myeloid leukemia (AML). However, patients treated with this regimen inevitably relapse and subsequent treatment options are limited. Furthermore, the success of this combination in the relapsed/refractory setting has been less impressive. Mechanisms of resistance to HMA/VEN are of great interest, and alterations in leukemic cell metabolism have been implicated. It is hypothesized that drugs that target oxidative phosphorylation (OXPHOS), fatty acid metabolism, and /or amino acid metabolism may be successful in overcoming HMA/VEN resistance. OPB-111077 is a novel, oral, low-molecular-weight compound that was shown in preclinical models to inhibit mitochondrial electron transport and have an inhibitory effect on the growth of AML cells. When given in combination with decitabine, OPB-111077 showed a more potent antitumor effect in a KG-1 tumor-bearing mouse model, thus providing support for conducting clinical trials of this combination. AML cells treated with OPB-111077 and venetoclax have also been shown to have decreased proliferation and increased apoptosis. The effects on proliferation and apoptosis of the combination of OPB-111077 and venetoclax were more pronounced in AML cells that were genetically engineered to increase OXPHOS. These data formed the basis for the development of a clinical trial utilizing the triplet of OPB-111077, decitabine, and venetoclax for the treatment of newly diagnosed or relapsed/refractory AML. Herein, we report results from the Phase Ib dose escalation study. Methods: In this phase Ib single center study (NCT03063944), OPB-111077 is administered daily starting on day 1 and continuing throughout the treatment cycle. Decitabine 20mg/m2 is given for 5 days starting on day 4 of cycle 1. Venetoclax 70mg daily (if receiving posaconazole prophylaxis) or 100mg daily (if receiving voriconazole) is started on day 4 and given continuously until day 28. If a response is seen within 2 cycles, treatment continues until toxicity, disease progression, or availability of an alternative therapy. Patients were enrolled in cohorts of escalating dose levels of OPB-111077 using a traditional 3+3 design. The primary objectives were to determine preliminary safety and tolerability as well as maximum tolerated dose (MTD) of OPB-111077. The secondary objective was to measure preliminary efficacy. Correlative studies including metabolomics, ATP measurement, apoptosis, and proliferative assays were performed on samples of blasts and non-cancerous cells that were collected from blood or marrow. Results: As of July 15, 2020, 2 patients with newly diagnosed AML and 7 patients with relapsed/refractory AML were treated with the triplet. Patients received OPB-111077 at 150mg (n=3), 200mg (n=3), and 250mg (n=3). Median age was 73 years (range, 23-79) and 7 patients (78%) were male. The median number of prior systemic anticancer regimens for patients with relapsed/refractory disease was 2 (range, 1-5); no patients had undergone prior stem cell transplant. The median treatment duration has not yet been reached; 3 patients are receiving ongoing treatment. No patients experienced a dose limiting toxicity. The most common Grade ≥3 adverse event (AE) was febrile neutropenia (56%). No patients discontinued due to AEs. No pts experienced tumor lysis syndrome. Three patients died after completing their study treatment, all due to progressive AML. The best overall response to therapy was a complete remission in 2 (22%) patients (1 with newly diagnosed AML and 1 with relapsed/refractory disease). Metabolomics using liquid chromatography/mass spectrometry was performed on paired pre- and post-treatment samples and intracellular metabolic changes in glycolysis and the tricarboxylic acid (TCA) cycle were observed consistent with on-target effects. Conclusion: The triplet of OPB-111077, decitabine, and venetoclax for the treatment of newly diagnosed or relapsed/refractory AML was safe and well tolerated, and showed preliminary anti-leukemic efficacy. A planned expansion phase is underway utilizing the 250mg daily dose of OPB-111077. Disclosures Martinez-Outschoorn: Otsuka Pharmaceutical: Research Funding. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding. Kasner:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka Pharmaceutical: Research Funding.

scholarly journals Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study

2013 ◽  
Vol 24 (6) ◽  
pp. 1560-1567 ◽  
Author(s):  
B. Schultheis ◽  
G. Folprecht ◽  
J. Kuhlmann ◽  
R. Ehrenberg ◽  
U.T. Hacker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Phase Ib ◽  
Multicenter Phase

scholarly journals Chloroquine combined with concurrent radiotherapy and temozolomide for newly diagnosed glioblastoma: a phase IB trial

Autophagy ◽  
2020 ◽  
pp. 1-9 ◽  
Author(s):  
Inge Compter ◽  
Danielle B. P. Eekers ◽  
Ann Hoeben ◽  
Kasper M. A. Rouschop ◽  
Bart Reymen ◽  
...  
Keyword(s):  
Newly Diagnosed ◽  
Phase Ib ◽  
Concurrent Radiotherapy ◽  
Newly Diagnosed Glioblastoma

T3 : A Multicenter Phase IB Dose Escalation Study to Evaluate the Safety, Feasibility and Efficacy of the Temsirolimus (Torisel™)-CHOP-Rituximab (T-R-CHOP), Temsirolimus (Torisel™)-FC-Rituximab (T-R-FC) and Temsirolimus (Torisel™)- DHA-Rituximab (T-R-DHA) for the Treatment of Patients with Relapsed/Refractory Mantle Cell Lymphoma (MCL), a Lysa Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4426-4426
Author(s):  
Steven Le Gouill ◽  
Krimo Bouabdallah ◽  
Guillaume Cartron ◽  
Remy Gressin ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Chemotherapy Regimen ◽  
Cell Lymphoma ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Multicenter Phase ◽  
Mantle Cell ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

Abstract The T3 trial is a multicenter Phase IB dose escalation study that evaluates the safety, feasibility and efficacy of three Temsirolimus-based chemotherapy regimens: Temsirolimus(Torisel™)-CHOP-Rituximab (T-R-CHOP), Temsirolimus(Torisel™)-FC-Rituximab (T-R-FC) and Temsirolimus(Torisel™)-Dexamethasone-aracytine-Rituximab (T-R-DHA) for the treatment of patients with relapsed/refractory Mantle Cell Lymphoma (MCL). The choice of the chemotherapy regimen was left to the decision of local investigator. The primary objective of the T3 was to assess the feasibility and incidence of dose limiting toxicities (DLT) during the two first cycles for each chemotherapy regimen in order to determine the maximal tolerate dose (MTD) in a 3+3 dose escalating design. Dose levels of Temsirolimus (administrated at D2, 8 and 15) were as followed: 25mg level 1; 50mg level 2 and 75mg level 3 and 15 mg in level -1. Patients were planned to receive at least 4 cycles. After 4 cycles, response was evaluated and then patients could continue treatment for 2 additional cycles or receive another treatment according to investigator’s decision. The T3 trial started in November 2011 and so far 38 patients have been enrolled (32 patients are evaluable to date; median age of 69y; range 56 -79). Before inclusion into the T3 trial, patients had received a median of 1 (range 1-3) line of treatment including autologous stem cell transplantation in 15 cases. Nine patients were included in the R-CHOP group (ORR after 4 cycles was 55,6%). In level 1, two patients out of 3 experimented DLT (grade 3: lymphopenia and GI hemorrhage). In level -1 (n=6), one DLT has been reported (grade 3 thrombocytopenia). In the T-R-FC group (n=12; ORR after 4 cycles was 41,7%), 6 patients were included in level 1 and 3 experimented DLT (grade 3: thrombocytopenia and leukopenia). In cohort -1 (n=6), 4 DLTs were reported. Eleven patients were included in the T-R-DHA group (ORR after 4 cycles was 80%). One DLT was suspected during toxicity review in level 1 (n=3) and was not confirmed as a DLT by the Safety Committee, hence the decision to pass to superior dose level. Then 6 patients (3+3) were included in level 2 (50mg) where 1 DLT was reported. However, only one patient received complete schema of temsirolimus with 3 injections because of hematology toxicity. Thus, it has been decided to add 3 additional patients at level 1 (25mg). These patients are currently under treatment. In conclusion, hematological toxicity grade 3 was the major concern of the three temsirolimus-based chemotheprapy regimen. Administration of Temsirolimus at D15 was frequently skipped. However, 51,6% of patients reached at least a PR after 4 cycles and the T-R-DHA group was the safest, in which, 50% of patients reached CR after 4 cycles. Thus, Temsirolimus plus high dose aracytine based-chemotherapy regimens provides good disease control with an acceptable tolerability profile for patients with relapsed MCL. Disclosures Le Gouill: pfizer: Honoraria; mundipharma: Honoraria; roche: Honoraria; celgene: Consultancy, Honoraria; janssen-cilag: Honoraria. Coiffier:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Phase Ib study of cediranib in combination with daily temozolomide and radiation in patients with newly diagnosed glioblastoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13010-e13010
Author(s):  
A. S. Chi ◽  
E. R. Gerstner ◽  
A. F. Eichler ◽  
H. K. Chea ◽  
J. Drappatz ◽  
...  
Keyword(s):  
Dose Level ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Tumor Control ◽  
Vegf Receptor ◽  
Newly Diagnosed ◽  
Tumor Biopsy ◽  
Phase Ib ◽  
Post Radiation ◽  
Grade 3

e13010 Background: Pre-clinical evidence suggests antiangiogenic therapy combined with radiation therapy (RT) and chemotherapy may improve tumor control in patients with glioblastoma (GBM). We conducted a phase Ib study to evaluate the safety and maximum tolerated dose (MTD) of the combination of cediranib, a potent pan-VEGF receptor tyrosine kinase inhibitor, standard RT, and temozolomide (TMZ) in patients with newly diagnosed GBM who were not taking enzyme-inducing antiepileptic drugs (EIAED). Methods: After undergoing tumor biopsy or resection, six patients with pathologically confirmed GBM were treated with concurrent TMZ (75mg/m2/day), RT (60 Gy) and cediranib (dose level 1 = 20mg/day; dose level 2 = 30mg/day) followed by post-radiation TMZ (150–200 mg/m2 on days 1–5 of each 28 day cycle) and cediranib (45mg/day) for up to 6 monthly cycles. Cediranib was started concurrently with RT and TMZ 14–21 days after surgery. Results: Six patients were treated (cediranib 20mg = 3 patients; cediranib 30mg = 3 patients). No patients experienced a DLT, establishing the MTD for cediranib in combination with RT and TMZ as 30mg/day in this patient population. Expected toxicities of hypertension, fatigue, and palmar/plantar erythema were observed. During combined cediranib and TMZ therapy in the post-radiation setting, one patient discontinued cediranib because of toxicity (grade 3 transaminase elevation) and one patient required dose reduction to 15mg/day due to grade 3 proteinuria. No intratumoral or intracerebral hemorrhages were observed during the course of cediranib treatment. No cases of wound infection or wound dehiscence were observed. All patients are alive with a median follow-up of 156 days. Conclusions: Cediranib given in combination with standard RT and TMZ for newly diagnosed GBM patients not on EIAEDs is well tolerated and the MTD is 30mg/day. The phase II component of this trial is underway and will include correlative biomarker and MRI studies. [Table: see text]

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