GLS-010, a novel anti-PD-1 mAb in Chinese patients with relapsed or refractory classical Hodgkin’s lymphoma: Preliminary result of a phase II clinical trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14072-e14072
Author(s):  
Yuqin Song ◽  
Jun Zhu ◽  
Ningjing Lin ◽  
Chen Zhang ◽  
Mingzhi Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neutrophil Count ◽  
Stable Disease ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Chinese Patients ◽  
Current Evidence ◽  
Fixed Dose ◽  
Favorable Result ◽  
Phase 2

e14072 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Previous Phase 1 study exhibited favorable result of tolerance, preliminary efficacy and 240mg fixed dose q2w was selected as Recommended Phase 2 Dose (RP2D). This Phase 2 clinical trial is aimed to further evaluate the safety and efficacy profile of GLS-010 in Chinese patients(pts) with relapsed or refractory classical Hodgkin’s Lymphoma( r/r cHL). Here we reported the preliminary result. Methods: All pts enrolled received GLS-010 240mg every 2 weeks. Tumor response was assessed by Lugona 2014 every 8 weeks. Adverse events (AEs) were graded by NCI CTCAE v4.03. Results: Until Jan 30th 2019, 39 pts were enrolled in this ongoing study. The median dosing number was 4 (range: 1~12). 17 pts received response evaluation. Of 17 evaluable subjects, an objective response was reported in 15 patients (88.3%), including 4(23.5%) pts with a complete response(CR) and 11 pts(64.7% )with a partial response(PR), 1 patient(5.9%) with stable disease(SD)and 1 remaining patient(5.9%) with unconfirmed progressive disease(PD)(observed stable disease(SD) in the first assessment).The most common treatment related AEs included Neutrophil count decreased (10/32), White blood cell count decreased (7/32), Fever (6/32), Alanine aminotransferase increased (4/32), etc. Treatment–related grade 3-5 AEs include Neutrophil count decreased (2/6), Interstitial lung disease (1/6), Influenza like illness (1/6). Conclusions: GLS-010 showed impressive therapeutic activity and an acceptable safety profile in Chinese r/r cHL patients. Current evidence support further development of GLS-010 in this and more indications. Clinical trial information: NCT03655483.

Gls-010, a novel anti-PD-1 mAb in Chinese patients with recurrent or metastatic cervical cancer: Results from a multicenter, open-label and single-arm phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Xiaohua Wu ◽  
Lingfang Xia ◽  
Qi Zhou ◽  
Jianqing Zhu ◽  
Ke Wang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cervical Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Chinese Patients ◽  
Current Evidence ◽  
Fixed Dose ◽  
Favorable Result ◽  
Open Label ◽  
Duration Of Response

6032 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Previous Phase I study exhibited favorable result of tolerance, preliminary efficacy and 240mg fixed dose q2w was selected as Recommended Phase II Dose (RP2D). This Phase II clinical trial is aimed to further evaluate the safety and anti-tumor activity of GLS-010 in patients with recurrent or metastatic cervical cancer. Methods: PD-L1 positive (combined positive score (CPS) ≥1) patients with recurrent or metastatic cervical cancer who had received one or more lines of chemotherapy were enrolled and received GLS-010 240mg every 2 weeks. Primary endpoint was the objective response rate (ORR) per RECIST 1.1, secondary endpoints included duration of response (DoR) and safety. Results: From May 16th 2019 to December 24th 2019, 44 pts were enrolled and treated in the study. As of December 24th 2019,the median line of prior systemic chemotherapy was 2(range: 1~4), and 59% (26/44) of pts had received ≥2 previous lines of chemotherapy. The median number of GLS-010 doses was 1.5(range: 1~4). 25 pts received response evaluation per investigator review. With a median follow-up of 2.9 months, 7 of 25 evaluable pts achieved a partial response (PR). The ORR was 28% (95% CI, 12.07-49.39), with 7 pts achieving a PR ( 3 of 7 confirmed), 3 pts achieving stable disease (SD) and 15 pts with progressive disease (PD), 1 of which was assessed as dissociated response with treatment ongoing. Median duration of response had not been reached yet. 33 of 44 patients (75%) experienced one or more treatment-related adverse events (TRAEs) per NCI CTCAE v4.03, most of which were grade 1 or 2. The most common TRAEs were Anaemia (15/44), and 73.3% of them were grade 1 or 2. The most common ≥grade 3 TRAE included Anaemia (4/44). As data cut off, only 1 pt discontinued treatment due to adverse event. Conclusions: GLS-010 showed impressive therapeutic activity and manageable safety profile in Chinese recurrent or metastatic cervical cancer patients. Current evidence support further development of GLS-010 in this and more indications. This trial is still ongoing, and we are looking forward to further results. Clinical trial information: NCT03972722.

Clinical Study Of Dose-Adjusted EPOCH Regimen For Non-Hodgkin's Lymphoma With Hemophagocytic Lymphohistiocytosis: Preliminary Results Of An Ongoing Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4360-4360
Author(s):  
Wei Xu ◽  
Lei Fan ◽  
Li Wang ◽  
Ji Xu ◽  
Run Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Progression ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hodgkin’S Lymphoma ◽  
Chemotherapy Regimen ◽  
Hodgkin's Lymphoma ◽  
Phase 2 ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Ongoing Phase

Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS) is characterized by cytokines storm and uncontrolled activation of macrophages. Secondary HLH in adults may occur in different occasions, including infections, autoimmune diseases, carcinomas and hematologic malignancies, in which Lymphoma-associated hemophagocytic lymphohistiocytosis(LA-HLH) has a high fatality rate and the worst outcome. The major cause of LA-HLH is aggressive non-Hodgkin's lymphoma (NHL), especially T/NKT cell lymphomas. Until now, there is no recommended therapeutic schedule for this fatal disease. Because of promising results of etoposide-containing regimen for HLH and high effective of continuous infusion chemotherapy regimen for aggressive NHL .The investigators therefore employed an intensive chemotherapy regimen--DA-EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) to treat non-Hodgkin's lymphoma with hemophagocytic lymphohistiocytosis and we have performed a preliminary analysis of this ongoing Phase 2 study and evaluated safety and efficacy of this regimen. Methods The clinical trial was designed as a prospective, multicenter, single-arm phase 2 clinical trial (NCT01818908). Enrolled patients included those with previously untreated NHL, and met the diagnostic criteria of either HLH2004 or ASH 2009 of HLH, patients with primary HLH and secondary HLH other than NHL were excluded. Therapeutic protocol of DA-EPOCH regimen was as follows: etoposide 50 mg/m2 CI 24h d1-d4, doxorubicin 10 mg/m2 CI 24h d1-d4, vincristine 0.4 mg/m2 CI 24h d1-d4, cyclophosphamide 750 mg/m2 IV d5, prednisone 60 mg/m2 oral d1-d5, If enrolled patient was histologically confirmed CD20+ B cell lymphoma, standard dose of rituximab will be recommended to combine with DA-EPOCH regimen. Drug dose was adjusted as previously described (Wyndham H. et al, 2002), each cycle of treatment was administered every 21 to 28 days according to recovery of toxicities. For patients who responded to the treatment and did not have disease progression, interim evaluation was conducted after 3 cycles of treatment. Results At the time of analysis 26 patients were enrolled and 20 patients were eligible to evaluate. Patients were 60.0% (12/20) male with median age 44(range: 14-60), the age-adjusted international prognostic score (aaIPI) enrolled to study was high/intermediate (2 score) 10/20, high risk group (3 score) 10/20. Histologies were four B-NHL, ten T-NHL and six NK-NHL. The median number of cycles of therapy was 3, patients who had discontinued study were mainly due to rapid disease progression. The overall response rate (ORR) among treated pts was 50.0%, with 35.0% (7/20) of patients achieving CR/CRu and 15.0% (3/20) achieving PR, and 50.0% of patients (10/20) had PD. With the median follow-up of 8 months, progression-free survival (PFS) rate was 46.3% and in subgroup analysis, PFS of B-NHL, T-NHL and NK-NHL was 75%, 45.7% and 25% respectively (Fig. 1); Overall survival (OS) rate was 52.4%(Fig. 2) and 75.0%, 58.3%, 22.2% in subgroup of B-NHL, T-NHL and NK-NHL(Fig. 3). The most common grade ≥3 treatment-related side effects were hematologic toxicities including neutropenia and thrombocytopenia. Conclusions Lymphoma-associated hemophagocytic lymphohistiocytosis progresses rapidly and has a high mortality rate, our preliminary results suggest DA-EPOCH regimen has acceptable toxicities and promising activity in NHL with HLH, especially for B-NHL and T-NHL, but prognosis of NK-NHL with HLH remains dismal, urgent need for novel therapeutic strategies may benefit the survival of patients with this disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin's lymphoma--a randomized multicenter study. The European Study Group of Erythropoietin (Epoetin Beta) Treatment in Multiple Myeloma and Non-Hodgkin's Lymphoma

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2675-2682 ◽  
Author(s):  
A Osterborg ◽  
MA Boogaerts ◽  
R Cimino ◽  
U Essers ◽  
J Holowiecki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Regression Analysis ◽  
Recombinant Human Erythropoietin ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Fixed Dose ◽  
Control Group ◽  
Human Erythropoietin ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

One hundred twenty-one anemic, transfusion-dependent patients with multiple myeloma (MM) or low-grade non-Hodgkin's lymphoma (NHL) were randomly allocated to receive (a) recombinant human erythropoietin (rhEPO) 10,000 U/d subcutaneously 7 days a week (fixed dose group) (n = 38), or (b) rhEPO 2,000 U/d subcutaneously for 8 weeks followed by step- wise escalation of the rhEPO dose (titration group) (n = 44), or (c) no rhEPO therapy (control group) (n = 39). The total treatment period was 24 weeks. There were no differences between the three groups with regard to baseline clinical, demographic, or health status measures. The cumulative response frequency, defined as elimination of the transfusion need in combination with an increase in the hemoglobin concentration by >20 g/L, was 60% in both rhEPO treatment groups and 24% in the control group (P = .01 and .02, respectively, log rank test). For patients in the titration group the response rate on the first dose level (2,000 U/d) was only 14%. Cox's univariate regression analysis revealed that an inadequately low endogenous erythropoietin concentration in relation to the degree of anemia and a baseline platelet concentration > or = 100 x 10(9)/L were significant predictors for response to rhEPO therapy (P < .01). Multivariate regression analysis showed that relative erythropoietin concentration was the most important factor and the platelet count had no additional influence on response. Treatment with rhEPO was well tolerated. We conclude that treatment with rhEPO may be indicated in anemic MM and NHL patients with a relative erythropoietin deficiency. An initial dose of 5,000 U/d subcutaneously may be recommended.

scholarly journals International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1460-1463 ◽  
Author(s):  
J Hermans ◽  
AD Krol ◽  
K van Groningen ◽  
PM Kluin ◽  
JC Kluin-Nelemans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Population Based ◽  
Hodgkin's Lymphoma ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Evaluation of neutropenia-related outcomes in Hodgkin's lymphoma patients with moderate or severe neutropenia who received ABVD chemotherapy without using granulocyte-colony stimulating factor

2019 ◽  
Vol 26 (4) ◽  
pp. 929-932
Author(s):  
Alparslan Merdin ◽  
Merih Kızıl Çakar ◽  
Mehmet Sinan Dal ◽  
Duygu Mert ◽  
Jale Yıldız ◽  
...  
Keyword(s):  
Neutrophil Count ◽  
Significant Relationship ◽  
Hodgkin’S Lymphoma ◽  
Lung Toxicity ◽  
Hodgkin's Lymphoma ◽  
Severe Neutropenia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Abvd Chemotherapy

Objective To evaluate the possible neutropenia-related effects of administering adriamycin [doxorubicin], bleomycin, vinblastin, dacarbazine (ABVD) chemotherapy in Hodgkin’s lymphoma patients with moderate or severe neutropenia without granulocyte-colony stimulating factor supplementation. Methods This study evaluated neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use during the periods between chemotherapy rounds. Forty-three rounds of ABVD chemotherapy were evaluated in the study. The outcomes that could be related to neutropenia were analyzed. In addition, rounds of ABVD chemotherapy given in the presence of severe neutropenia were compared with ABVD chemotherapy rounds given in the presence of moderate neutropenia in terms of neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use. The study only included patients with classical Hodgkin's disease (lymphoma). Patients with a final neutrophil count of <1 × 103 cells/µL (<1000 cells/µL) prior to chemotherapy round and those receiving ABVD chemotherapy for Hodgkin’s lymphoma were included in the study. Results We observed that none of the patients with moderate neutropenia before the start of chemotherapy round needed granulocyte-colony stimulating factor, and four patients with severe neutropenia prior to the start of chemotherapy round required granulocyte-colony stimulating factor. However, there was no statistically significant relationship between the severity of neutropenia (in terms of moderate and severe) before chemotherapy and granulocyte-colony stimulating factor requirement after chemotherapy (p> 0.05). Furthermore, none of the patients included in the study had bleomycin-related lung toxicity during the treatment periods included in the study. Conclusion Administering ABVD chemotherapy to patients with moderate neutropenia seems to be safe.

Chimeric Anti-CD20 Monoclonal Antibody (Rituximab; Mabtheraâ) in Remission Induction and Maintenance Treatment of Relapsed /Resistant Follicular Non-Hodgkin’s Lymphoma : A Phase III Randomized Intergroup Clinical Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 586-586 ◽  
Author(s):  
Marinus H.J. Van Oers ◽  
Martine Van Glabbeke ◽  
Ivana Teodorovic ◽  
Cynthia Rozewicz ◽  
Richard Klasa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Hodgkin’S Lymphoma ◽  
Maintenance Treatment ◽  
Initial Diagnosis ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Remission Induction ◽  
Non Hodgkin's Lymphoma

Abstract Background. In view of a) the efficacy of Rituximab (R) monotherapy in relapsed low grade lymphoma; b) the feasibility to combine R with cytostatic drugs c) the potential of such combinations to clear minimal residual disease, in 1999 we started a phase III clinical trial in patients with relapsed follicular non-Hodgkin’s lymphoma, with 2 main objectives. First: to compare CHOP and R-CHOP as to response rate and response quality. Second: to establish the effect of maintenance treatment with R on progression-free survival (PFS ). Study design. Patients with stages III or IV follicular lymphoma at initial diagnosis and relapsed after or resistant to a maximum of two non-anthracycline containing systemic chemotherapy regimens, were randomized to remission induction with either 6 cycles of standard CHOP (once every 3 weeks) or CHOP + R (375 mg /m2 at day 1 of each cycle of CHOP). Those with a complete or partial remission after 6 cycles of therapy underwent a second randomization to no further treatment or maintenance treatment with R (375 mg/m2 once every 3 months until relapse or for a maximum period of two years). Results. In February 2004, a preplanned second interim analysis by the IDMC was performed. At that time 461 patients had been included. Of these, 369 could be evaluated for response (188 CHOP; 181 R-CHOP). The groups did not differ as to age, sex, performance status, time from initial diagnosis, number and type of, and best overall response to prior chemotherapy. Both treatment arms yielded similar PR rates: CHOP 53.7%; R-CHOP 52.5 %. However, there was a highly significant difference in CR rates: CHOP 18.1% versus R-CHOP 30.4 % (p=0.0004). 319 patients have been randomized for maintenance treatment. Of these, 268 were evaluable (132 observation; 136 R maintenance). 1 year and 3 year PFS were 54.9% and 31.2% respectively in the observation arm, and 80.2 % and 67.7% in patients with R maintenance treatment (p< 0.0001). There is as yet no impact on OS: the observed difference (in favor of R maintenance) was not significant for an interim analysis (p=0.03). There were no differences in toxicity between CHOP and R-CHOP induction treatments. Maintenance treatment was associated with minimal toxicity. Because the planned second interim analysis revealed that the primary endpoints for both the induction and maintenance part of the study had been reached, the formal criteria for stopping the trial have now been met. Conclusion. In patients with relapsed/resistant follicular lymphoma R-CHOP remission induction results in a highly significant increase in CR rate as compared to CHOP. Moreover, this is the first trial to show that in these patients Rituximab maintenance treatment achieves a considerable improvement in PFS.

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