Flavopiridol Can Be Safely Administered Using a Pharmacologically Derived Schedule and Demonstrates Activity In Relapsed and Refractory Non-Hodgkin's Lymphoma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2834-2834
Author(s):  
Jeffrey A. Jones ◽  
Leslie Andritsos ◽  
Robert Baiocchi ◽  
Don M Benson ◽  
Kristie A. Blum ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Hodgkin's Lymphoma ◽  
Hematologic Toxicity ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3 ◽  
Elevated Transaminases

Abstract Abstract 2834 Background: A phase 2 study of flavopiridol administered according to a pharmacokinetically- (PK-) derived schedule has demonstrated significant activity in CLL, irrespective of high-risk genomic features. In combination with fludarabine and rituximab, flavopiridol has further shown promising activity in mantle cell lymphoma (MCL) and indolent B-cell non-Hodgkin's lymphoma (NHL). However, the safety and efficacy of single-agent flavopiridol administered on this schedule has not yet been characterized in patients with relapsed/refractory NHL. Methods: We conducted a standard cohorts-of-3 phase 1 trial to determine the maximum tolerated dose (MTD) and safety of single-agent flavopiridol in each of 4 groups: indolent B-NHL, aggressive B-NHL, MCL, and T-NHL. Adult patients (age >18y) with previously-treated (T-NHL '1 prior; B-NHL ≥2 prior), preserved end-organ function, adequate hematologic parameters (unless attributable to disease), and preserved performance status (≤ECOG 2) were eligible. Further, pts were only eligible if they had exhausted all other therapeutic options. All pts signed informed consent. Flavopiridol was given as a 30 min loading dose followed by a 4 hr infusion weekly for 4 weeks of a 6 week cycle (max 6 cycles). Dose levels (DL) 1, 2, and 3 were 30 mg/m2 + 30 mg/m2, 30 mg/m2 + 50 mg/m2, and 50 mg/m2 + 50 mg/m2, respectively. The first infusion was administered in hospital, but treatment could continue outpatient thereafter. Pts received allopurinol, phosphate binders, and Kayexalate (if pre-treatment K+ >4.5) prophylaxis for tumor lysis syndrome (TLS). Steroid pre-medication and/or treatment for cytokine release syndrome (CRS) was given at the discretion of the treating clinician. Dose-limiting toxicity (DLT) was generally defined as any grade 3/4 non-hematologic toxicity not resolving to ≤grade 2 within 2 wks or any grade 4 hematologic toxicity (except leukopenia/neutropenia) resulting in >1 wk treatment delay. Results: 28 pts evaluable for toxicity have thus far completed cycle 1, which was used to define DLT: median age 66 years (range 34–84), 13 female (46%), median prior therapies 3 (range 1–8). All B-NHL patients received prior rituximab. Subsequent dose evaluation continues in the MCL and T-NHL arms. Across all pt groups, there were 11 pts at DL 1, 11 pts at DL 2, and 6 pts at DL 3. No DLTs have been observed to date. Median number of cycles received was 2. Seven pts completed all 6 cycles: 4 pts 30+30, 2 pts 30+50, 1 pt 50+50. Although no DLTs were observed, grade 3/4 hematologic toxicity was seen in 26 pts: neutropenia (23 pts), thrombocytopenia (3 pts), and anemia (7 pts). Grade 3 neutropenic fever and infection, however, were only observed in 2 and 5 pts, respectively. Common grade 3 non-hematologic toxicities included diarrhea (15 pts), fatigue (8 pts) and elevated transaminases (3 pts). Grade 3 CRS and TLS occurred in only 2 pts, both during cycle 1. Only 2 grade 4 non-hematologic toxicities (elevated transaminases, elevated lipase) were observed, both of which resolved without sequelae. Among pts completing ≥1 cycle, the most common reason for discontinuing treatment was disease progression (17 pts). One pt withdrew after diagnosis of a second cancer, 2 pts proceeded to transplant, and 2 pts withdrew for toxicity (1 persistent fatigue, 1 persistently elevated transaminases/malaise). Four pts expired on study: 3 progression, 1 sudden cardiac death unrelated to flavopiridol. Of 26 pts evaluable for response, 6 pts (21%) had partial responses: 2 follicular (30+30, 30+50), 1 SLL (50+50), 2 MCL (30+30, 30+50), and 1 DLBCL (50+50). Seven pts had stable disease for ≥1 cycle: 1 follicular (30+50), 1 MCL (30+30), 1 Richter's CLL (30+30), 1 DLBCL (50+50), and 3 PTCL (2 pts 30+30, 1 pt 30+50). Conclusions: Administered according to a PK-derived schedule, single-agent flavopiridol can be successfully delivered to multiply relapsed and/or refractory NHL pts with acceptable hematologic and non-hematologic toxicity. Both the promising activity and relative safety observed in these heavily pre-treated NHL pts warrant further investigation of this agent earlier in the course of disease and/or in combination with other agents, particularly in indolent B-cell and mantle cell NHL. Disclosures: Blum: Celgene : Research Funding.

Phase II Multicenter Study of Bendamustine Plus Rituximab in Patients With Relapsed Indolent B-Cell and Mantle Cell Non-Hodgkin's Lymphoma

2008 ◽  
Vol 26 (27) ◽  
pp. 4473-4479 ◽  
Author(s):  
K. Sue Robinson ◽  
Michael E. Williams ◽  
Richard H. van der Jagt ◽  
Philip Cohen ◽  
Jordan A. Herst ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

PurposeBendamustine HCl is a bifunctional mechlorethamine derivative with clinical activity in the treatment of non-Hodgkin's lymphoma. This study evaluated bendamustine plus rituximab in 67 adults with relapsed, indolent B-cell or mantle cell lymphoma without documented resistance to prior rituximab.Patients and MethodsPatients received rituximab 375 mg/m2intravenously on day 1 and bendamustine 90 mg/m2intravenously on days 2 and 3 of each 28-day cycle for four to six cycles. An additional dose of rituximab was administered 1 week before the first cycle and 4 weeks after the last cycle. Sixty-six patients (median age, 60 years) received at least one dose of both drugs.ResultsOverall response rate was 92% (41% complete response, 14% unconfirmed complete response, and 38% partial response). Median duration of response was 21 months (95% CI, 18 to 24 months). Median progression-free survival time was 23 months (95% CI, 20 to 26 months). Outcomes were similar for patients with indolent or mantle cell histologies. The combination was generally well tolerated; the primary toxicity was myelosuppression (grade 3 or 4 neutropenia, 36%; grade 3 or 4 thrombocytopenia, 9%).ConclusionBendamustine plus rituximab is an active combination in patients with relapsed indolent and mantle cell lymphoma.

Phase I trial of combination therapy with 90Y ibritumomab tiuxetan and gemcitabine in patients with non-Hodgkin’s lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17514-17514
Author(s):  
H. Borghaei ◽  
M. Smith ◽  
M. Millenson ◽  
K. Krieger ◽  
A. Rogatko ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Hematologic Toxicity ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

17514 Background: Zevalin (Z) is an effective therapy in patients with relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). Gemcitabine (gem) also is active against NHL and is a potent radiation sensitizer. We are conducting a phase I trial to assess the safety of concomitant administration of Z and gem in patients with NHL. Methods: The starting gem dose is 250 mg/m2 on days 1 and 8. Nine patients in three cohorts will be treated with 250 mg/m2 of gem with 0.2, 0.3 or 0.4 mCi/kg of Z. The next cohort can accrue after all patients in the prior cohort have hematologic toxicity has recovered to grade 2 or after 60 days from the date of the last treated patient in the previous cohort. Once it is confirmed that a Z dose of 0.4 mg/kg can be safely administered with gem 250 mg/m2, gem will be escalated according to a Bayesian based system. Response evaluation is based on the International Workshop on Standardized Response Criteria for Non-Hodgkin’s lymphomas. Eligibility criteria include: any histology of recurrent NHL (not candidates for high dose therapy), platelets ≥ 150,000/ul; < 25% bone marrow involvement by lymphoma; prior radiation to < 25% radiation of bone marrow and no prior bone marrow or stem cell transplant. Results: Five patients have been treated thus far, two with follicular NHL (FL) and three with diffuse large B cell (DLBCL). Median age is 75 (range 55–82). The median number of prior treatments is 2 (range 1–6). One patient with DLBCL is not evaluable. The first three patients received 0.2 mCi/kg and next two patients 0.3 mCi/kg of Zevalin. Toxicity consists of grades 2 & 3 myelosuppression in the first 3 weeks in 3 pts. due to gem and then of grade 2 in 1 pt. at 6 to 8 weeks as is usually seen with Z. One grade 3 leukopenia and one grade 2 thrombocytopenia have been observed resolving within one week. One grade 3 infection occurred, unrelated to the protocol or the study drugs. No grade 3 or 4 non-hematologic toxicity has been seen. In follow up, two patients with FL and one with DLBCL achieved CRu. One patient with DLBCL has progressed and one is not yet evaluable. Conclusions: Our preliminary findings suggest that Z can be safely combined with gem 250 mg/m2 in the treatment of patients with NHL. Dose escalation to full dose Zevalin and then of gemcitabine is continuing. [Table: see text]

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.

A Multicenter Phase II Trial of Etoposide, Methylprednisolone, High-Dose Cytarabine, and Oxaliplatin (ESHAOx) for Patients with Refractory/Relapsed Aggressive Non-Hodgkin’s Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3446-3446
Author(s):  
Sun Jin Sym ◽  
Hye Jin Kang ◽  
Seung-Hyun Nam ◽  
Hoyoung Kim ◽  
Seok Jin Kim ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Hematopoietic Stem ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
High Dose Cytarabine

Abstract Etoposide (E), methylprednisolone (S), high-dose cytarabine (HA), and cisplatin (P) (ESHAP) combination is commonly used salvage regimen for non-Hodgkin’s lymphoma (NHL). Oxaliplatin (Ox), a new platinum derivative, showed substantially different cytotoxic activity and adverse effects from both cisplatin and carboplatin. In addition, single-agent oxaliplatin was reportedly active in patients with NHL. We conducted to investigate the efficacy and toxicity of ESHAOx combination, substituting oxaliplatin for cisplatin in ESHAP combination, for relapsed/refractory aggressive NHL patients. Main eligibility criteria included aggressive NHL and failure to achieve a complete remission or recurrent disease after previous chemotherapy. ESHAOx consisted of E, 40 mg/m2 on days 1 to 4; S, 500 mg on days 1 to 5; HA, 2 g/m2 on day 5; and Ox, 130 mg/m2 on day 1, every 3 weeks. Eligible patients were scheduled to receive a maximum of 6 cycles, and high dose chemotherapy and hematopoietic stem cell rescue allowed. Responses were evaluated every 3 cycles. All patients gave written informed consent before study entry. Between May 2006 and January 2007, 27 patients were enrolled. Nineteen (70%) patients with relapsed, 8 patients with refractory, and 10 (37%) patients with IPI 3–5 were included in this study. A total of 102 cycles were administered for a median number of 4 (range 1–6 cycles) per patient. There were 8 (30%) complete responses and 9 (33%) partial responses, producing an overall response rate of 63% (95% CI, 45–81%). Most common grade 3/4 toxicity of the courses was myelosuppression with including neutropenia (55%) and thrombocytopenia (33%). Non-hematologic toxicity was very favorable. No significant renal and neurotoxicity was demonstrated. There was one treatment-related death due to neutropenic sepsis. The results of ESHAOx combination showed highly antitumor activity and favorable toxicity profile, suggesting it can be used as salvage regimen for relapsed/refractory aggressive NHL patients.

Phase I Trial of Combination Therapy with 90Y Ibritumomab Tiuxetan and Gemcitabine in Patients with Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4710-4710
Author(s):  
Hossein Borghaei ◽  
Mitchell Smith ◽  
Michael Millenson ◽  
Danielle Shafer ◽  
Linda Thibodeau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

Abstract Y90-ibritumomab tiuxetan, or Zevalin (Z), is an effective therapy against CD20+ lymphomas and is approved for use in patients with relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). Gemcitabine also is active against NHL and is a potent radiation sensitizer. We are conducting a phase I trial to assess the safety of concomitant administration of Z and gemcitabine in patients with NHL. Nine patients in three cohorts will be treated with 250 mg/m2 of gemcitabine IV on days 1 and 8 of the Z treatment program of rituximab + In 111-ibritumomab on day 1 and rituximab + Y90 ibritumomab on day 8, with Z at 0.2, 0.3 or 0.4 mCi/kg respectively. The next cohort can only accrue after all patients in the prior cohort have hematologic toxicity that has recovered to grade 0–2 or after 60 days from the date of the last treated patient in the previous cohort. Once it is confirmed that a Z dose of 0.4 mg/kg can be safely administered with gemcitabine 250 mg/m2, Z will remain constant at 0.4 mCi/kg while gemcitabine will be escalated according to a Bayesian based system. Response evaluation is by standard criteria. Eligibility criteria include: any histology of recurrent NHL (not candidates for high dose therapy), platelets ≥ 150,000/ul; &lt; 25% bone marrow involvement by lymphoma; prior radiation to &lt;25% radiation of bone marrow and no prior bone marrow or stem cell transplant. Seven patients have been treated thus far, four with follicular NHL (FL) and three with diffuse large B cell (DLBCL). Median age is 74 (range 55–82). The median number of prior treatments is 3 (range 1–6). The first three patients received Z at 0.2 mCi/kg, next three patients 0.3 mCi/kg and the seventh patient has received standard 0.4 mCi/kg of Z, all with 250 mg/m2 of gemcitabine on days 1 and 8. Toxicity has consisted of: one grade 3 and two grade 2 neutropenia in the first three weeks, three grade 3 leukopenia and one grade 2 in the first 4 weeks of the trial, three grade 2 anemia (one patient has remained with grade 2 anemia for 14 weeks), four grade 2 thrombocytopenia in weeks 6 through 12, and one grade 3 thrombocytopenia in weeks 8&9 resolving to grade 2 (this patient received standard dose of Z). One grade 3 infection occurred, unrelated to the protocol or the study drugs. No grade 3 or 4 non-hematologic toxicity has been seen. In follow up, two patients with FL and one with DLBCL achieved CRu. Two patients with DLBCL and one with FL have progressed. One patient with FL is not yet evaluable. Conclusion: Our preliminary findings suggest that Zevalin can be safely combined with gemcitabine 250 mg/m2 in the treatment of patients with NHL. Accrual to the cohort with full dose Zevalin and gemcitabine is continuing.

Phase II Study of Rituximab Combined with Cladribine and Mitoxantrone in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4946-4946
Author(s):  
Shuichi Ota ◽  
Junji Tanaka ◽  
Masanobu Nakata ◽  
Kiyotoshi Imai ◽  
Masahiro Ogasawara ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Median Time ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Severe Neutropenia ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

Abstract BACKGROUND. Synergistic or additive activities for rituximab and cladribine have been shown in preclinical studies. Indolent Non-Hodgkin’s lymphoma (I-NHL) tends to recur with shortening intervals of remission after standard chemotherapy. New modalities of treatment are necessary. Therefore, we evaluated the feasibility, efficacy, and toxicity of combined regimen that consisted of rituximab plus cladribine plus mitoxantrone (the RCM regimen) in the treatment of patients with relapsed or refractory I-NHL. METHODS. The RCM protocol consisted of rituximab at a dose of 375 mg/m2 on Day 1, cladribine at a dose of 0.09 mg/kg per day on Days 2 through 6, and intravenous mitoxantrone at a dose of 6 mg or 10 mg/m2 per day on Day 2. The RCM courses were repeated at 4-week intervals, for up to 4 cycles. RESULTS. Fourteen patients with I-NHL and one patient with mantle cell lymphoma entered in the study. The median age was 60 (range 47–77) and 8 were females. Histology was small lymphocytic lymphoma (n=1), follicular lymphoma (n=13), mantle cell lymphoma (n=1). Median time from diagnosis to RCM treatment was 3.6 (range 0.2–8.1) years and median number of prior treatment regimen was 2 (range 1–4). Twelve patients (80%) had recurrent disease after prior therapy including high dose therapy with autologous stem cell transplant, and 3 patients (20%) had refractory disease. Thirteen patients were treated on the RCM regimen, and 8 patients (61.5%) achieved a complete response, 3 patients (23.1%) achieved a partial response. Therefore, the overall response rate was 92.3%. Median time to response was 2.8 months (range 1.0–6.7). Median progression free survival of responders was 16.5 (range 1.3–25.5) months. The treatment revealed tolerability, with episodes of severe neutropenia (grade 3 and 4) observed in 12 patients (85.7%), episodes of grade 3 and 4 thrombocytopenia observed in 2 patients (15.4%). However, severe infections were not observed in any patients. CONCLUSIONS. The RCM regimen is highly effective and well tolerated modalities of treatment in heavily pretreated and relapsed or refractory patients with I-NHL.

Osteopenia and osteoporosis in untreated non-Hodgkin's lymphoma patients: An important and potentially treatable survivorship issue in lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9055-9055 ◽  
Author(s):  
M. A. Thompson ◽  
A. Huen ◽  
B. B. Toth ◽  
R. Vassilopoulou-Sellin ◽  
A. O. Hoff ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Loss ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Alkylating Agents ◽  
Hodgkin's Lymphoma ◽  
Mineral Density ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell

9055 Background: Alkylating agents and steroids can cause premature osteoporosis, increasing the risk of vertebral and hip fracture. The bisphosphonate pamidronate every 3 months can reduce bone loss and the risk of new vertebral fractures in lymphoma patients receiving chemotherapy.(Kim et al., 2004 Am J Med) We are conducting a randomized study of the more potent bisphosphonate zoledronic acid in untreated non-Hodgkin's lymphoma (NHL) patients to study chemotherapy induced bone loss. Methods: During the accrual period, we report the baseline bone mineral density (BMD) characteristics for screened untreated NHL patients. Exclusion criteria included bone fractures, BMD T-scores worse than -2.0, CrCl < 60 mL/min, dental problems, prior bisphosphonate or significant steroid use. Patients accrued to the study were randomized to receive either: 1) oral calcium and vitamin D (Ca+D) or 2) Ca+D and 4 mg zoledronic acid IV at baseline and at 6 months. Results: Patient characteristics: 59 males and 55 females with median age 63 (range: 18–87). Lymphoma types: B-cell n=111, T-cell 3; follicular (FL) 56, diffuse large B-cell (DLBCL) 33, mantle cell 8, and others, totaling 114 patients. Of untreated NHL individuals screened for baseline BMD to date 11/114 (10%) had osteoporosis and 62/114 (54%) had osteopenia or osteoporosis. The lowest BMD was a T-score of -4.4. Other bone, dental, and endocrine abnormalities excluded some patients from treatment randomization. Patients with T scores < -2.0 were considered for off-study treatment with bisphosphonates. Osteopenia and osteoporosis were common across lymphoma subtypes: FL 25/56 (45%), DLBCL 20/33 (61%), mantle cell 6/8 (75%), and marginal zone 5/6 (83%). The low rate of osteopenia/osteoporosis of 25% for Burkitt/Burkitt-like lymphoma may reflect fast lymphoma kinetics without associated increase in bone loss. Conclusions: Baseline testing of BMD revealed osteopenia or osteoporosis in the majority of untreated NHL patients. This widely available and non-invasive test should be considered in untreated NHL patients. Our ongoing clinical trial will address the potential role of zoledronic acid in preserving bone density for survivors of NHL. ClinicalTrials.gov Identifier: NCT00352846 [Table: see text]

Phase IIa study of single-agent MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8500-8500 ◽  
Author(s):  
Wojciech Jurczak ◽  
Pier Luigi Zinzani ◽  
Andre Goy ◽  
Mariano Provencio ◽  
Zsolt Nagy ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Phase II Window Study on Rituximab in Newly Diagnosed Pediatric Mature B-Cell Non-Hodgkin's Lymphoma and Burkitt Leukemia

2010 ◽  
Vol 28 (19) ◽  
pp. 3115-3121 ◽  
Author(s):  
Andrea Meinhardt ◽  
Birgit Burkhardt ◽  
Martin Zimmermann ◽  
Arndt Borkhardt ◽  
Udo Kontny ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Corticosteroid Treatment ◽  
Hodgkin's Lymphoma ◽  
Newly Diagnosed ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL. Patients and Methods Patients younger than age 19 years with CD20+ B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m2 administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had ≥ 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity. Results From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007). Conclusion Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.

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