Multicenter Phase II Clinical Study of Iodine-131–Rituximab Radioimmunotherapy in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma

2006 ◽  
Vol 24 (27) ◽  
pp. 4418-4425 ◽  
Author(s):  
Michael F. Leahy ◽  
John F. Seymour ◽  
Rodney J. Hicks ◽  
J. Harvey Turner
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Whole Body ◽  
Actuarial Survival ◽  
Entire Cohort ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Iodine 131

Purpose To evaluate efficacy and safety of iodine-131 (131I) –rituximab chimeric anti-CD20 antibody radioimmunotherapy in patients with relapsed or refractory indolent non-Hodgkin's lymphoma (NHL). Patients and Methods After a standard loading dose of rituximab 375 mg/m2, individualized dosimetry was performed by whole-body gamma imaging of a tracer activity of 131I-rituximab followed by administration of a therapeutic activity of 131I-rituximab to deliver an estimated whole-body radiation absorbed dose of 0.75 Gy. Results Ninety-one patients were entered onto the trial: 78 patients (86%) had follicular lymphoma, six patients (7%) had mucosa-associated lymphoid tissue/marginal zone lymphoma, and seven patients (8%) had small lymphocytic lymphoma. The objective overall response rate (ORR) was 76%, with 53% attaining a complete response (CR) or CR unconfirmed (CRu). Median duration of response for patients achieving CR/CRu was 20 v 7 months for those with a partial response (P = .0121). Median progression-free survival for the entire cohort was 13 months, with 14% remaining relapse free beyond 4 years. Median follow-up was 23 months, with a 4-year actuarial survival rate of 59% ± 10%. Toxicity was principally hematologic; grade 4 thrombocytopenia occurred in 4% and neutropenia occurred in 16% of patients, with nadirs at 6 to 7 weeks after treatment. Conclusion 131I-rituximab radioimmunotherapy of relapsed or refractory indolent NHL achieves high ORR and CR rates with minimal toxicity.

Histologic conversion in the non-Hodgkin's lymphomas.

1983 ◽  
Vol 1 (1) ◽  
pp. 11-16 ◽  
Author(s):  
B Acker ◽  
R T Hoppe ◽  
T V Colby ◽  
R S Cox ◽  
H S Kaplan ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Randomized Clinical Trials ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Whole Body ◽  
Actuarial Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Actuarial Risk ◽  
Hodgkin's Lymphomas

Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkin's lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkin's lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.

Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma.

1993 ◽  
Vol 11 (10) ◽  
pp. 2021-2029 ◽  
Author(s):  
M S Czuczman ◽  
D J Straus ◽  
C R Divgi ◽  
M Graham ◽  
P Garin-Chesa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antitumor Activity ◽  
Dose Escalation ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Whole Body ◽  
Fixed Dose ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Iodine 131

PURPOSE Eighteen patients with recurrent or refractory CD21-positive, non-Hodgkin's lymphoma (NHL) were treated in a phase IA dose-escalation therapeutic trial of iodine 131 labeled to a fixed dose of OKB7. METHODS Individual doses of 30 to 50 mCi of 131I on 25 mg OKB7 were administered 2 to 3 days apart to achieve four total 131I-OKB7 dose levels of 90, 120, 160, and 200 mCi. Pharmacology, dosimetry, therapeutic effects, toxicity, human anti-mouse antibody (HAMA) response, and maximum-tolerated dose (MTD) were determined. Patients were evaluated by imaging studies (including whole-body gamma camera or single-photon emission computed tomography [SPECT] scans), flow cytometric analysis, bone marrow biopsy, and serial blood sampling. RESULTS Median plasma and whole-body half-lives (T1/2) were 16 hours and 14 hours, respectively. Plasma and whole-body radiation doses were 0.0081 Gy/mCi and 0.0022 Gy/mCi, respectively. Specific tumor visualization was noted in eight of 18 patients. HAMA was detected in 12 of 16 patients. Nonhematologic toxicity was limited to asymptomatic elevations of thyroid-stimulating hormone (TSH) in five of 15 patients. Hematologic toxicity was observed in six of 18 patients, but was severe in only two patients. MTD in patients with diffuse lymphomatous bone marrow involvement was determined to be 200 mCi in four divided doses of 50 mCi 131I/25 mg OKB7. Antitumor activity was observed in 13 of 18 patients (one partial response [PR] and 12 mixed responses) and was dependent on the 131I-OKB7 dose administered. In general, palpable peripheral lymphadenopathy, enlarged spleens, skin lesions, and circulating OKB7-positive peripheral lymphocytes responded most readily to treatment. 131I-OKB7 was safely administered to a patient in leukemic phase of NHL with prompt subsequent loss of approximately 1 kg of tumor cells from the peripheral blood without associated tumor lysis syndrome. CONCLUSION Because antitumor activity with tolerable toxicity was observed in the majority of this group of heavily pretreated patients, phase II investigation of mAb OKB7 radioconjugates in the therapy of NHL is warranted.

Bendamustine in Patients With Rituximab-Refractory Indolent and Transformed Non-Hodgkin's Lymphoma: Results From a Phase II Multicenter, Single-Agent Study

2008 ◽  
Vol 26 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Philip Cohen ◽  
Ling Chen ◽  
K. Sue Robinson ◽  
Andres Forero-Torres ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Patients Âgés ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Duration Of Response

PurposeBendamustine hydrochloride is an alkylating agent with novel mechanisms of action. This phase II multicenter study evaluated the efficacy and toxicity of bendamustine in patients with B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab.Patients and MethodsPatients received bendamustine 120 mg/m2intravenously on days 1 and 2 of each 21-day cycle. Outcomes included response, duration of response, progression-free survival, and safety.ResultsSeventy-six patients, ages 38 to 84 years, with predominantly stage III/IV indolent (80%) or transformed (20%) disease were treated; 74 were assessable for response. Twenty-four (32%) were refractory to chemotherapy. Patients received a median of two prior unique regimens. An overall response rate of 77% (15% complete response, 19% unconfirmed complete response, and 43% partial) was observed. The median duration of response was 6.7 months (95% CI, 5.1 to 9.9 months), 9.0 months (95% CI, 5.8 to 16.7) for patients with indolent disease, and 2.3 months (95% CI, 1.7 to 5.1) for those with transformed disease. Thirty-six percent of these responses exceeded 1 year. The most frequent nonhematologic adverse events included nausea and vomiting, fatigue, constipation, anorexia, fever, cough, and diarrhea. Grade 3 or 4 reversible hematologic toxicities included neutropenia (54%), thrombocytopenia (25%), and anemia (12%).ConclusionSingle-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL. These findings are promising and will serve as a benchmark for future clinical trials in this novel patient population.

High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma

2010 ◽  
Vol 28 (23) ◽  
pp. 3709-3716 ◽  
Author(s):  
Franck Morschhauser ◽  
Françoise Kraeber-Bodéré ◽  
William A. Wegener ◽  
Jean-Luc Harousseau ◽  
Marie-Odile Petillon ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Complete Response ◽  
Multicenter Trial ◽  
Hodgkin's Lymphoma ◽  
Bulky Disease ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20

Purpose Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). Patients and Methods A multicenter trial evaluated two or three weekly infusions of yttrium-90 (90Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. Results At the maximum total 90Y dose of 45 mCi/m2 (1,665 MBq/m2), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and 90Y doses, even in poor-risk categories (refractory to last anti-CD20–containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total 90Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m2 total 90Y-dose [1,110 MBq/m2]). Further, patients with FL refractory to prior anti-CD20–containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. Conclusion Fractionated anti-CD22 radioimmunotherapy provides high total doses of 90Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m2 × 2 weeks as the recommended dose for future studies.

Fludarabine-Based Regimens in the Treatment of Indolent Non-Hodgkin’s Lymphoma Patients: A Clinical Study of the Fludarabine Cooperation Group in 16 Hospitals in Eastern China.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4753-4753
Author(s):  
Junmin Li
Keyword(s):  
Clinical Study ◽  
Hodgkin’S Lymphoma ◽  
Eastern China ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Multi Center Study

Abstract Objective: We performed this prospective, multi-center study to evaluate the efficacy and safety of fludarabine-based regimes in the treatment of previously untreated and refractory, or relapsed, indolent non-Hodgkin’s lymphoma (NHL). Methods: Two fludarabine-based regimens were used in the clinical study. The FC regimen which consisted of fludarabine 50 mg/day, and cyclophosphamide 200 mg/day, intravenously, for 3 consecutive days, was given to the previously untreated patients. The FMD regimen which consisted of fludarabine 50 mg/day, intravenously, for 3 consecutive days, mitoxantrone 10 mg/m2, intravenously, on the first day, and dexamethasone 20 mg/m2/day, intravenously, for 5 consecutive days, was given to the relapsed and refractory patients. Results: Forty-seven indolent NHL patients (29 male and 18 female) were enrolled in this study from February 2003 to May 2005. The main disease subtypes were: chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL; n = 25), follicular lymphoma (FL; n = 18), lymphoplasmic lymphoma (LPL; n = 3), marginal zone lymphoma (MZL; n =1). Overall response (OR) rate was 93.62%, and 44 of 47 patients achieved a response. The complete response (CR) rate was 63.83%, and 30 of 47 patients achieved a response. In the 16 previously untreated patients, the CR rate was 75.0% (n =12); the OR rate was 93.8% (n = 15). In the 31 relapsed and refractory patients, the CR rate was 61.3% (n =19) and OR rate was 93.5% (n =29). Median patient follow-up was 12 months (range, 1–27 months). The 12-month progression free survival (PFS) rates of previously untreated patients and relapsed or refractory patients were 93.3±6.4% and 91.04±6.1%, respectively; and the 18-month overall survival (OS) rates were 90.9±8.67% and 90.32±6.90%, respectively. Both regimens were well tolerated and the major toxicities were bone marrow suppression and gastrointestinal response. Conclusion: The FC and FMD regimens are effective and safe for indolent NHL patients.

Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

2009 ◽  
Vol 27 (32) ◽  
pp. 5404-5409 ◽  
Author(s):  
Thomas E. Witzig ◽  
Peter H. Wiernik ◽  
Timothy Moore ◽  
Craig Reeder ◽  
Craig Cole ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Wide Range

Purpose Lenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Patients and Methods Patients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety. Results Forty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusion Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.

Utility of PET/CT for therapy response assessment in non-Hodgkin's lymphoma

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Sally Mahmoud Abdel-Aziz Abdel-Aziz ◽  
Safaa Kamal Mohamed BadrElden ◽  
Asmaa Magdy Mohamed Salama
Keyword(s):  
Ct Scan ◽  
Hodgkin’S Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Whole Body ◽  
Non Hodgkin’S Lymphoma ◽  
Contrast Enhanced Ct ◽  
Pet Ct ◽  
Non Hodgkin's Lymphoma ◽  
Enhanced Ct

Abstract Aim of the study to evaluate the role of PET/CT in initial diagnosis and staging of lymphoma, and to determine the predictive value of 18F-FDG PET by monitoring the early response and final response after completion of chemotherapy in patients with non-Hodgkin's lymphoma. Patient and Methods our prospective study included 25 patients with pathologically confirmed nonHodgkin Lymphoma diffuse large B cell lymphoma selected from Department of Radiology at Ain Shams University Hospital from January 2019 to March 2020. The patients included in this study performed the followings: Initial PET/CT for staging, interim PET/CT and end of the treatment PET/CT. We performed low dose non enhanced CT scan first, then a whole body PET study followed by diagnostic enhanced whole body CT scan. The whole study took approximately 20-30 minutes. Results PET/CT has greater sensitivity 100% and specificity 68.8% than CT alone for detecting sites of nodal and extra-nodal involvement and for assessment of therapeutic response in non-Hodgkin lymphoma. Conclusion PET / CT is an accurate method for evaluating tumor viability in the post-therapy setting of Non-Hodgkin lymphomas. PET / CT has a significant advantage for the diagnosis of diffusely infiltrating organs without mass lesions or contrast enhancement compared to contrast enhanced CT.

scholarly journals A phase III, multicentric, open-label, two-arm, parallel group, active-control, randomized, comparative clinical study to evaluate efficacy and safety of RituxiRel™ arm (rituximab) with reference arm (rituximab) in patients with non-Hodgkin's lymphoma

2017 ◽  
Vol 03 (01) ◽  
pp. 017-022 ◽  
Author(s):  
Prasad Apsangikar ◽  
Sunil Chaudhry ◽  
Manoj Naik ◽  
Parvez Kozgi
Keyword(s):  
Partial Response ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Lymphatic System ◽  
Complete Response ◽  
Safety Analysis ◽  
Hodgkin's Lymphoma ◽  
Efficacy And Safety ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Introduction: Non-Hodgkin's lymphoma (NHL) is the sixth most common hematological malignancy in adults, with B-cell lymphomas accounting for 85% of all NHLs. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL and follicular lymphoma (FL) is the second most common form of B-cell NHL. Materials and Methods: The primary objective of this study is to assess the efficacy of Rituxirel™ arm with reference arm, whereas the secondary objective is to evaluate safety of Rituxirel™ arm with the reference arm in patients diagnosed with NHL. Results: The first patient was enrolled on April 30, 2012 and the efficacy and safety analysis was performed at 24 weeks. The objective response rate (ORR) was observed to be 87.87% in Rituxirel™ arm. 45.45% patients showed complete response and 42.42% patients showed partial response in Rituxirel™ arm. The ORR was observed to be 86.66% in the reference arm. 33.33% patients showed complete response and 53.33% patients showed partial response in reference arm in the Rituxirel™ arm, the most commonly reported treatment-emergent adverse events (TEAEs) related to blood and lymphatic system disorders were 52.94%, whereas in the reference arm, the reported TEAEs related to blood and lymphatic system disorders were 70%. Conclusion: Based on the results from the efficacy and safety analysis at week 24, Rituxirel™ arm was found to be as effective and safe as the reference arm. Rituxirel™ arm can be a prudent option to the reference arm, in patients undergoing treatment for DLBCL or FL.

Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma.

1998 ◽  
Vol 16 (10) ◽  
pp. 3246-3256 ◽  
Author(s):  
G L DeNardo ◽  
S J DeNardo ◽  
D S Goldstein ◽  
L A Kroger ◽  
K R Lamborn ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Radiation Dosimetry ◽  
Large Cell ◽  
Maximum Tolerated Dose ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Iodine 131 ◽  
Grade 3 ◽  
Dose Limiting Toxicity

PURPOSE Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. MATERIALS AND METHODS Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1 and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. RESULTS Mean radiation dose to the bone marrow from body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14 entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION (131)I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).

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