Phase I/II Dose-Escalation Study of Tositumomab and Iodine I 131 Tositumomab for Relapsed/Refractory Classical or Lymphocyte-Predominant Hodgkin’s Lymphoma: Feasibility and Initial Safety

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3059-3059 ◽  
Author(s):  
Heather A. Jacene ◽  
Yvette L. Kasamon ◽  
Richard F. Ambinder ◽  
Wayne Kasecamp ◽  
Donna Serena ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Phase I ◽  
Dose Escalation ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Cd20 Expression ◽  
Grade 3 ◽  
Experienced Grade ◽  
131I Tositumomab

Abstract Objective : CD20 has been recently recognized as a potential immunotherapeutic target in Hodgkin’s lymphoma (HL), being expressed in all malignant cells in lymphocyte-predominant HL (LPHL), a subset of classical HL (cHL), and in normal surrounding B-cells. Recent data also suggest that the cancer stem cell in cHL is phenotypically distinct from Reed-Sternberg cells and expresses B-cell antigens including CD20 (Jones RJ et al, Blood2006; 108: abstract 470). Given the single agent activity of the unlabeled antiCD20 monoclonal antibody, rituximab, in HL, we are conducting a phase I/II study of tositumomab and Iodine I 131 (131I-) tositumomab (BEXXAR ®, GlaxoSmithKline) for HL in the relapsed/refractory setting, regardless of tumor CD20 expression. We report on feasibility and initial safety. Methods : Separate dose-escalation studies were performed for patients with and without prior stem cell transplantation, starting at 55 and 75 cGy total body radiation doses (TBD), respectively. Dosimetry imaging studies were performed after administration of 450 mg tositumomab and 5 mCi 131I-tositumomab. Patients then received a single patient-specific therapeutic dosage of 450 mg tositumomab and 131I-tositumomab. The TBD was escalated or de-escalated based on a continual reassessment method (CRM). Results : Seven patients with relapsed/refractory disease (6 cHL, 1 LPHL; mean age 36 ± 9) have been enrolled. Four patients with cHL were negative for CD20 on malignant Reed-Sternberg cells and two had mixed expression. Three patients who had failed transplant received a 55 cGy TBD of 131I-tositumomab and three ineligible for transplant received 75 cGy. No dose-limiting toxicities were observed and based on the CRM, the TBD was escalated to 79 cGy for the post-transplant group and to 87 cGy for the no transplant group. To date, one in the next post-transplant cohort received 79 cGy and experienced grade 1 thrombocytopenia and grade 3 lymphopenia with count recovery. No adverse reactions occurred during infusion of unlabeled or radiolabeled tositumomab, and the agent was generally well-tolerated in all dosing cohorts. The expected hematologic adverse events were common and are summarized in the Table. No patients experienced grade 3 or 4 non-hematologic toxicity. One patient had grade 1 or 2 fever, chills, joint and muscle pain suggesting possible human anti-mouse antibody formation and immune complex mediated inflammation. One patient with LPHL had a complete response, two with cHL had stable disease (1 mixed CD20 expression, 1 CD20 negative) and 4 with cHL had progressive disease (1 mixed CD20 expression, 3 CD20 negative) at 12 weeks post-131I-tositumomab. Conclusions : Tositumomab and 131I-tositumomab can be safely administered to patients with relapsed/refractory HL. Major toxicities are hematologic, similar to its effect in patients with non-Hodgkin’s lymphoma. The CRM was used successfully for determining TBD for subsequent cohorts, and the transplant recipients have tolerated higher doses than those previously reported in non-Hodgkin’s lymphoma. These encouraging preliminary data support further dose escalation and suggests some therapeutic effect of tositumomab and 131I-tositumomab against HL. Hematologic Adverse Events All (n=7) Grade Range of Duration of Grade 3/4 Toxicity (days) 1/2 3 4 Thrombocytopenia 6 0 1 1 7–34 Neutropenia 2 1 0 1 7 Lymphopenia 7 2 3 2 1–35 Anemia 2 1 1 0 4

Phase I Study of the Humanized Anti-CD40 Monoclonal Antibody Dacetuzumab in Refractory or Recurrent Non-Hodgkin's Lymphoma

2009 ◽  
Vol 27 (26) ◽  
pp. 4371-4377 ◽  
Author(s):  
Ranjana Advani ◽  
Andres Forero-Torres ◽  
Richard R. Furman ◽  
Joseph D. Rosenblatt ◽  
Anas Younes ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Phase I Study ◽  
Hodgkin’S Lymphoma ◽  
Vision Loss ◽  
Hodgkin's Lymphoma ◽  
Open Label ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

PurposeTo evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in patients with refractory or recurrent B-cell non-Hodgkin's lymphoma (NHL).Patients and MethodsIn this open-label, dose-escalation phase I study, dacetuzumab was administered to six cohorts of adult patients. In the first cohort, patients received 2 mg/kg weekly for 4 weeks; in all other cohorts, an intrapatient dose-escalation schedule was used with increasing doses up to a maximum of 8 mg/kg. Patients with clinical benefit after one cycle of dacetuzumab were eligible for a second cycle.ResultsIn the 50 patients who received dacetuzumab, no dose dependence of adverse events (AEs) was observed. The most common AEs in ≥ 20% of patients were fatigue, pyrexia, and headache; most were grade 1 or 2. Noninfectious inflammatory eye disorders occurred in 12% of patients. AEs grade ≥ 3 occurred in 30% of patients and included disease progression, anemia, pleural effusion, and thrombocytopenia. Most laboratory abnormalities were grade 1 or 2; transient elevated hepatic aminotransferases occurred in 52% of patients. Two patients experienced dose-limiting toxicity: grade 3 conjunctivitis and transient vision loss in cohort (1), and grade 3 ALT elevation in cohort IV. The MTD of dacetuzumab was not established at the dose levels tested. Six objective responses were reported (one complete response, five partial responses). Tumor size decreased in approximately one third of patients.ConclusionDacetuzumab monotherapy was well tolerated in patients with NHL in doses up to 8 mg/kg/wk. Preliminary response data are encouraging and support additional studies of dacetuzumab in this patient population.

A Phase I Study of Humanized Anti-CD40 Immunotherapy with SGN-40 in Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1504-1504 ◽  
Author(s):  
Ranjana H. Advani ◽  
Richard R. Furman ◽  
Joseph D. Rosenblatt ◽  
Anas Younes ◽  
Andres Forero-Torres ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase I ◽  
B Cell ◽  
Dose Escalation ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Ct Scans ◽  
Cytokine Release ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

Abstract The vast majority of B-cell malignancies express CD40, a member of the TNF receptor family. This receptor, along with the cognate ligand (CD154), mediates cell survival and proliferation of normal B-cells and can regulate apoptosis as well as survival in transformed cells, making this pathway an appealing target for B-cell lymphoma. Both in vitro and in vivo preclinical studies support the development of anti-CD40 immunotherapy for non-Hodgkin’s lymphoma (NHL). Accordingly, a phase I single-arm dose escalation trial was initiated to test the safety, pharmacokinetics, and antitumor activity of SGN-40, a humanized anti-CD40 antibody, in patients with NHL. The protocol was designed to treat patients with follicular, mantle cell, diffuse large B-cell, small lymphocytic, and marginal zone lymphomas in cohorts using SGN-40 infusions at doses of 2, 4, 8, or 16 mg/kg/week for four weeks. We report results for cohort 1 (n = 6) treated at 2 mg/kg/week. Four of 6 patients completed the planned 4 weekly infusions. No grade 4 toxicity was observed. Two grade 3 toxicities were seen, both in the same patient (unilateral conjunctivitis and ipsilateral loss of vision in a patient with pre-existing macular degeneration). Grade 2 loss of balance was also seen in the same patient. Imaging studies with CT and MRI did not reveal a stroke or leptomeningeal disease nor were there inflammatory or malignant cells in the CSF. All these adverse events resolved over six weeks, including vision which returned to baseline acuity. The only other severe adverse event reported was a deep venous thrombosis in the setting of bulky ipsilateral pelvic adenopathy, which was considered to be unrelated to SGN-40. Dose escalation was temporarily suspended to evaluate these unexplained toxicities and the report of severe headaches, attributed to cytokine release reaction, at the next dose level (i.e. 4 mg/kg) in a parallel phase I protocol for multiple myeloma. Although none of the NHL patients in this study developed headaches or clinical symptoms, several patients demonstrated a significant increase in plasma cytokine levels (i.e. TNF-alpha, IL-6) following the first infusion but not subsequent treatments with SGN-40, raising the possibility that a first-dose cytokine release effect may be involved in the grade 3 toxicities observed. Pharmacokinetic samples for the NHL patients were collected and are currently being analyzed. Preliminary antitumor activity at the 2 mg/kg dose is reflected in one patient who had stable disease as determined by serial CT scans and in another patient who had subjective improvement in B symptoms during therapy but was found to have disease progression based on CT scans 4 weeks after completing therapy. An amended protocol is actively accruing patients that will address the concern for first-dose cytokine release and allow continued dose escalation. Clinical and pharmacokinetic data from these additional cohorts will be presented.

First-line treatment with Bendamustine plus Rituximab for patients with indolent non-Hodgkin’s lymphoma or Mantle cell lymphoma: Real-world experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19540-e19540
Author(s):  
Rouslan Kotchetkov ◽  
David Susman ◽  
Lauren Gerard ◽  
Erica DiMaria ◽  
Derek Wayne Nay
Keyword(s):  
Adverse Events ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
First Line ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.

Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

2008 ◽  
Vol 26 (30) ◽  
pp. 4952-4957 ◽  
Author(s):  
Peter H. Wiernik ◽  
Izidore S. Lossos ◽  
Joseph M. Tuscano ◽  
Glen Justice ◽  
Julie M. Vose ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Common Grade ◽  
Duration Of Response ◽  
Grade 3 ◽  
Large B Cell

PurposeThe major cause of death in aggressive lymphoma is relapse or nonresponse to initial therapy. Lenalidomide has activity in a variety of hematologic malignancies, including non-Hodgkin's lymphoma (NHL). We report the results of a phase II, single-arm, multicenter trial evaluating the safety and efficacy of lenalidomide oral monotherapy in patients with relapsed or refractory aggressive NHL.Patients and MethodsPatients were treated with oral lenalidomide 25 mg once daily on days 1 to 21, every 28 days, for 52 weeks, until disease progression or intolerance. The primary end point was response; secondary end points included duration of response, progression-free survival (PFS), and safety.ResultsForty-nine patients with a median age of 65 years received lenalidomide in this study. The most common histology was diffuse large B-cell lymphoma (53%), and patients had received a median of four prior treatment regimens for NHL. An objective response rate of 35% was observed in 49 treated patients, including a 12% rate of complete response/unconfirmed complete response. Responses were observed in each aggressive histologic subtype tested (diffuse large B-cell, follicular center grade 3, mantle cell, and transformed lymphomas). Of patients with stable disease or partial response at first assessment, 25% improved with continued treatment. Estimated median duration of response was 6.2 months, and median PFS was 4.0 months. The most common grade 4 adverse events were neutropenia (8.2%) and thrombocytopenia (8.2%); the most common grade 3 adverse events were neutropenia (24.5%), leukopenia (14.3%), and thrombocytopenia (12.2%).ConclusionOral lenalidomide monotherapy is active in relapsed or refractory aggressive NHL, with manageable side effects.

Phase I Trial of CG53135-05 to Prevent Mucositis in Patients Undergoing High-Dose Chemotherapy (HDCT) and Autologous Peripheral Blood Stem Cell Transplantation (PBSCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1161-1161
Author(s):  
Michael W. Schuster ◽  
Tsiporah B. Shore ◽  
June Greenberg ◽  
Bita Jalilizeinali ◽  
Scott Possley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase I ◽  
Oral Mucositis ◽  
Phase I Trial ◽  
Study Drug ◽  
Great Promise ◽  
Cell Transplant ◽  
Conditioning Regimens ◽  
Grade 3 ◽  
Experienced Grade

Abstract Mucositis is a painful side effect of many transplant conditioning regimens used in HDC and PBSCT. This complication often requires treatment with potent narcotic analgesics and may even require intravenous patient-controlled analgesia (PCA) for adequate pain relief as well as total parenteral nutrition (TPN). Infections in this setting may also result from disruption of the mucosal barrier with subsequent migration of intestinal bacteria into the blood stream. Previous treatments with oral rinses and topical applications of soothing gels have largely been ineffective. Recently, a breakthrough class of drugs in the fibroblast growth factor (FGF) family holds great promise in more effectively ameliorating or even preventing oral mucositis (OM). We report on the results of a Phase I trial with CG53135-05, a novel investigational protein therapeutic (FGF-20) that promotes epithelial and mesenchymal cell proliferation in vitro and has demonstrated activity in animal models. 14 patients (ages 25–75) undergoing HDCT with PBSCT were treated with escalating doses of study drug, including 0.1 mg/kg, 0.2 mg/kg and 0.33 mg/kg (concentrations are determined by the UV method which are equivalent to 0.3, 0.6, and 1 mg/kg by the Bradford method previously used). Conditioning regimens used included melphalan (Mel 200), cyclophosphamide, carmustine and etoposide (CBV), carboplatin and thiotepa (CT), cyclophosphamide, etoposide and carmustine (CEC) and busulfan/cyclophosphamide (targeted BuCy). The primary objective of this phase I trial was to evaluate safety, tolerability and pharmacokinetics of CG53135-05. Patients (pts.) were also scored daily for presence of OM using both the WHO and OMAS (oral mucositis assessment scale) grading scales. 7/14 pts. in this study experienced no OM (including 2 Mel 200 patients), 5 pts. experienced only grade 1 OM. while 2 pts. (both treated with Mel 200) experienced grade 3 OM, and no pts. experienced grade 4 OM. 1 pt. experiencing grade 3 OM required TPN. Only 4 pts. experienced diarrhea that lasted more than 4 days and only 1 pt. had gut mucositis-associated (E. coli) bacteremia. The median day of engraftment (ANC>500/uL) occurred on day 14 (range: day 11–19). Patients tolerated the study drug well with no significant side effects up to a dose of 0.33 mg/kg. At that dose, 2 pts. experienced an infusional reaction consisting of fevers, nausea, and mild hypotension. Pharmacokinetics were measured at all dose levels and will be presented. CG53135-05 is a member of a breakthtrough drug class (FGF family) that was well tolerated in autologous stem cell transplant patients at doses up to 0.33 mg/kg with apparent clinical effects in ameliorating or preventing OM - 12/14 pts, thus, avoided severe (grades 3–4) mucositis following HDCT. A larger Phase II clinical trial is planned.

Gemcitabine, Vinorelbine and Dexamethasone (GVDexa) As Second-Line Salvage Regimen in Relapsed and Refractory Hodgkin's Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3948-3948
Author(s):  
Anjana Joel ◽  
Prasanth Ganesan ◽  
Tenali Gnana Sagar ◽  
Krishnarathnam Kannan ◽  
Trivadi Ganesan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Baseline Characteristics ◽  
Third Line ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract INTRODUCTION: Traditional platinum-based salvage regimens like DHAP, ICE are effective in relapsed Hodgkin's lymphoma (HL), but are more toxic. Gemcitabine based regimens are equally effective in salvage of lymphomas, but are less toxic and allow better stem cell collection for subsequent high dose therapy (HDT). There is limited data on the usefulness of gemcitabine based salvage regimens after the failure of salvage therapies like DHAP and ICE. At our center, we used a combination of gemcitabine, vinorelbine and dexamethasone (GVDexa), a non-platinum containing regimen in those patients who failed DHAP/ ICE based salvage treatment. METHODS: The records of patients with relapsed and refractory Hodgkin's lymphoma, who were treated with GVDexa, were reviewed. The regimen consisted of Gemcitabine 1000mg/m2 IV (D1,8), Vinorelbine 25mg/m2 IV (D1,8) Dexamethasone 40mg oral (D1-4) given as outpatient. It was given for 2-3 cycles until best response or till the patient underwent HDT. RESULTS: Between July 2010 to Jun 2015, 25 patients received GVDexa. The median age was 23 years (Range: 11 to 45 yrs) and 64% were males. Baseline characteristics are summarised in Table 1. Twenty-one patients (84%) had previous exposure to salvage therapy with DHAP/ ICE and GVDexa was given as third line treatment. The overall response rate was 48% (12/25) with complete response in 20% (5/25) and partial response in 28% (7/25). Toxicity: A total of 61 cycles [Median: 2 (Range: 1-6)] were delivered among 25 patients. Grade 3/4 haematological toxicities (neutropenia and thrombocytopenia) occurred in 9/61 (14.7%) cycles and febrile neutropenia occurred in 2 (3.2%) cycles. Grade 3/4 non-haematological toxicities were rare (paralytic ileus in 1 patient). There were no toxic deaths. Stem cell collection: Stem cell harvesting for HDT was attempted in 12 patients and was successful (> 2 million CD34 positive cells/kg) in 8 (67%) patients. Seven of these patients successfully completed HDT. Two patients who failed stem cell collection underwent reduced intensity conditioning allogeneic transplant. CONCLUSIONS: GVDexa, when used as third line therapy in relapsed and refractory HL shows promising response rates, with minimal toxicity. The high response rates achieved despite failure of first line platinum based salvage, points to the potential usefulness of this regimen as first line salvage therapy in refractory HL. GVDexa could emerge as a safe and effective non-platinum containing alternative regimen for second-line therapy in HL. Table 1. Baseline characteristics (N=25) PARAMETER Number (Range/Percentage) Age (median, range) 23 yrs (10 to 45 yrs) Male sex 16 (64%) Prior exposure to DHAP/ICE chemotherapy 21 (84%) Previous lines of chemotherapy (median, range) 2 (1 to 4) Time from 1st diagnosis to relapse (median, range) 31.5 months (4.3 to 153.7 months) Primary progressivea/refractory 13 (52) Stage III/IV at relapse 20 (80) Haemoglobin < 10g/dL at relapse 12 (48) a. Progressed within 3 months of completion of first line chemotherapy Disclosures No relevant conflicts of interest to declare.

Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 490-490 ◽  
Author(s):  
Fatima A. Rangwala ◽  
Johanna C. Bendell ◽  
Mark Kozloff ◽  
Christy Arrowood ◽  
Jennifer Meadows ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Rectovaginal Fistula ◽  
Dose Intensity ◽  
Advanced Solid Tumors ◽  
Increased Risk ◽  
Level 1 ◽  
Grade 3

490 Background: Everolimus (E), an oral rapamycin analogue, is a potent mTOR inhibitor. Combined inhibition of VEGF and mTOR pathways may increase anti-angiogenic and anti-tumor activity. We evaluated E in combination with capecitabine (C), oxaliplatin (O), and bevacizumab (B) in a phase I dose escalation study. Methods: Eligible patients (pts) had advanced solid tumors, adequate organ function and no increased risk for class-related toxicities. B and O were given intravenously; C and E were orally administered. Cycle length was 21 days. Doses for level 1: C 850 mg/m2 on days 1-14; O 130 mg/m2 on day one; B 7.5 mg/kg on day one; and E 5 mg three times a week. Doses for level -1: C 680 mg/m2, O100mg/m2. An intermediate dose level (-1b) of E escalated to 5 mg five times weekly was added to maximize dose intensity. Dose limiting toxicity (DLT) was assessed in cycle 1. Concomitant administration of CYP3A4 substrates, inhibitors or inducers was prohibited. Results: Dose escalation is complete with 27 pts evaluable for toxicity and 24 evaluable for efficacy. Two DLTs (grade 2 intolerable fatigue, anorexia, vomiting and grade 3 diarrhea) were observed in 6 pts in cohort 1. No DLTs were observed in cohort -1; one DLT (rectovaginal fistula) was observed in the -1b cohort. Possible grade ≥3 treatment-related adverse events any time on study (n=1 except as indicated) included diarrhea (n=2), intestinal perforation/fistula, rectovaginal fistula, hypertriglyceridemia (n=3), hyperglycemia, hypoalbuminemia, hyponatremia, peripheral neuropathy, neutropenia (n=2), lymphopenia, thrombocytopenia, hypertension (n=3), deep vein thrombosis, and arterial thrombosis. Adverse events were consistent with known class-related toxicities. For efficacy, 10 pts had a partial response (PR); 10 had stable disease as best response. Of 13 pts with chemorefractory metastatic colorectal cancer (mCRC), 5 had a PR. Of 8 pts with chemonaive mCRC, 5 had a PR. Conclusions: E in combination with full dose C, O and B was associated with unacceptable toxicity, primarily GI toxicity. E at 5mg five times weekly, C at 680 mg/m2 on days 1-14, O at 100 mg/m2 and B at 7.5 mg/kg on day one appears well tolerated. Activity was noted in chemorefractory and chemonaive mCRC patients.

Phase II trial of GVDexa (gemcitabine, vinorelbine and dexamethasone) regimen in relapsed/refractory Hodgkin’s lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19519-e19519
Author(s):  
Nikita Mehra ◽  
Prasanth Ganesan ◽  
Jayachandran P K ◽  
Anjana Joel ◽  
Parathan Karunakaran ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Liposomal Doxorubicin ◽  
Objective Response ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Salvage Regimen ◽  
Grade 3

e19519 Background: Gemcitabine, vinorelbine and liposomal doxorubicin (GVD) is an effective regimen in relapsed/refractory Hodgkin’s lymphoma (RRHL). Conventional second-line chemotherapy is still required as the cost of immunotherapy and antibody-drug conjugates are prohibitive to Indian patients. We report the results of a phase II, open-label, single-arm, single centre interventional study in RRHL where dexamethasone replaced liposomal doxorubicin. Methods: Adult patients (≥18 years) with RRHL at first or second relapse were included. GVDex was delivered as outpatient once in 3 weeks (Gemcitabine 1000 mg/m2 IV over 30 min on D1,8; Vinblastine 25 mg/m2 IV fast infusion on D1,8; Dexamethasone 40 mg PO D1-4) for two cycles followed by interim PET CT assessment by Cheson’s criteria and Deauville scoring. The primary endpoint was the objective response rate (ORR = complete response + partial response). The sample size was calculated using Fleming’s 2-stage model (α error: 0.05 and power: 0.8). Twenty patients were required in the first stage. If there were ≥16 responses, the null hypothesis would be rejected and the study stopped. Results: Between May 2016, and December 2020, 26 patients with RRHL were screened, and 20 were enrolled: primary resistant HL-8 patients (40%) and relapsed HL- 12 patients (60%). The median age was 35 years (range:20-52). Six patients (30%) presented with limited stage and 14 patients (70%) with advanced stage HL at relapse. GVdex was delivered as a first salvage regimen in 18 patients (90%) and second in 2 patients. After 2 cycles of GVDex, 16 (80%) had responded [partial response: 12 (60%); complete response: 4 (20%)]. Median number of cycles of GVDex: 3 (range: 1-4). Five patients (25%) required dose reductions due to chemotherapy-related toxicities. The median duration of objective response was 13.4 months. Eleven patients (55%) underwent high-dose chemotherapy supported by autologous stem cell rescue. After a median follow-up of 25 months (95% CI: 5.9-44.5), the median progression-free survival (PFS) was 24.7 months, and the median overall survival (OS) has not been reached. The estimated 2-year PFS was 44%, and the 2-year OS was 79%. The most common treatment-related adverse events were anemia (100%), neutropenia (70%, 14/20) and fatigue (70%, 14/20). Grade 3 or 4 treatment-related AEs occurred in 14 patients (70%). Grade ≥3 neutropenia occurred in 9 patients (45%) and febrile neutropenia in 3 patients (15%). Serious adverse events were reported in 3 patients (15%). One patient developed Ficat and Arlet classification stage III avascular necrosis of the femoral head. One patient died due to suspected COVID-19 pneumonia (non-neutropenic fever) before cycle 2 of chemotherapy. Conclusions: GVDex it is an effective salvage regimen with acceptable toxicity in patients with RRHL. Clinical trial information: CTRI/2017/04/008361.

Sign in / Sign up

Export Citation Format

Share Document