Phase II study of combination therapy with CHOP Interferon (IFN) alpha and rituximab (R) in chemo-naive patients (pts) with diffuse large B cell non-Hodgkin’s lymphoma (NHL)

Abstract Background: Pixantrone is a novel aza-anthracenedione with less cardiotoxicity and superior activity compared to doxorubicin and mitoxantrone in murine leukemia and lymphoma tumor models. Pixantrone as single agent therapy led to major responses in patients (pts) with multiply relapsed aggressive non-Hodgkin’s lymphoma (NHL), including diffuse large B-cell lymphoma (DLCL). In a phase I dose-ranging study of pixantrone (80 to 180 mg/m2) replacing doxorubicin (CPOP) in a CHOP-like regimen, the optimal dose (RD) from that study was found to be 150 mg/m2. Methods: In this international, multi-center, phase II study the primary objective was to assess the efficacy and safety of the CPOP regimen (cyclophosphamide 750 mg/m2d1, pixantrone 150 mg/m2d1, vincristine 1.4 mg/m2 d1, limited to 2 mg, and prednisone 100mg d1 to 5) in pts with relapsed DLCL, transformed follicular lymphoma (tFL) and mantle cell lymphoma (MCL) for a total of 6 cycles, given every 3 weeks. Response was assessed according to the standardized response criteria for NHL. Hematopoietic growth factors were not permitted for the first cycle and were used thereafter according to the ASCO guidelines. Main eligibility criteria included at least one but not more than two previous chemotherapy lines containing an anthracycline/anthracenedione with a cumulative dose of less than 450 mg/m2doxorubicin equivalent, a left ventricular ejection fraction (LVEF) > 50%, absence of CNS lymphoma, and negative HIV serology. Results: Thirty pts were included in this phase II study and are available for efficacy and safety assessment. Main baseline characteristics were: median age, 66 y (range 26–76); median baseline International Prognostic Index (IPI), 2 (11/30 pts had IPI 3 or 4); median number of previous therapy lines, 2 (1–7); median time since last chemotherapy, 14 months (1–202). Median number of cycles of study drug received was 6 (1–6). The overall response rate (ORR) was 73%, with 14 (47%) pts achieving complete response (CR/CRu) and 8 (26%) pts with partial responses (PR). For responses lasting at least 8 weeks (63%), the median duration of response was 10.3 months (range 2.5 to 27). The most common severe toxicities were gr 3/4 neutropenia, 29 (97%) pts; gr 3 febrile neutropenia, 6 (20%); gr 3 anemia, 9 (30%); gr 3/4 thrombocytopenia, 6 (20%); gr 3/4 infections, 5 (17%). Four pts had a decrease in LVEF >10% and ≤20% as determined by MUGA-scan. One of these patients developed symptomatic right heart failure classified by the investigator as related to progressive NHL. Two pts experienced transient LVEF decline > 20% during long-term follow up. Conclusions: The CPOP combination therapy with 150 mg/m2 pixantrone results in a high ORR (73%) with 47% CRs. Furthermore, it exhibits an acceptable toxicity profile and can be administered safely in an outpatient setting even in this cohort of elderly, anthracycline-pretreated patients. Based on these results, a randomized Phase II study comparing CPOP-rituximab with CHOP-rituximab in patients with untreated diffuse large-B-cell NHL has been initiated.

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Phase II Study of Denileukin Diftitox for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2004.03.071 ◽

2004 ◽

Vol 22 (20) ◽

pp. 4095-4102 ◽

Cited By ~ 79

Author(s):

Nam H. Dang ◽

Fredrick B. Hagemeister ◽

Barbara Pro ◽

Peter McLaughlin ◽

Jorge E. Romaguera ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Stable Disease ◽

Hodgkin’S Lymphoma ◽

Phase Ii Study ◽

Hodgkin's Lymphoma ◽

Low Grade ◽

Denileukin Diftitox ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

Purpose Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. Patients and Methods Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 μg/kg once daily for 5 days every 3 weeks, up to eight cycles. Results Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25− histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. Conclusion Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25− B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.

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Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin’s lymphoma

Annals of Hematology ◽

10.1007/s00277-014-2269-8 ◽

2015 ◽

Vol 94 (4) ◽

pp. 633-641 ◽

Cited By ~ 22

Author(s):

Myron S. Czuczman ◽

Stephen Kahanic ◽

Andres Forero ◽

Glen Davis ◽

Mihaela Munteanu ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Hodgkin’S Lymphoma ◽

Phase Ii Study ◽

Hodgkin's Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

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Phase II study of cladribine with rituximab (R-2-CdA) therapy in patients with relapsed indolent B-cell non-Hodgkin's lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e19501 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e19501-e19501

Author(s):

H. Nagai ◽

S. Kusumoto ◽

K. Sawada ◽

M. Yamaguchi ◽

N. Takayama ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Hodgkin’S Lymphoma ◽

Phase Ii Study ◽

B Cell Lymphoma ◽

Hodgkin's Lymphoma ◽

Severe Neutropenia ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Previously Treated

e19501 Background: Although cladribine has been reported to be one of active purine analogs against indolent B-cell non-Hodgkin's lymphoma (B-NHL), there are few reports of combination usage of cladribine and rituximab. We conducted a multicenter phase II study to investigate efficacy and toxicity of cladribine with rituximab (R-2-CdA) therapy for relapsed indolent B-NHL. Methods: Eligibility criteria were as follows: relapsed pts with indolent B-NHL from systemic chemotherapy, ages less than 75 years; PS 0–2 by ECOG's scale. Patients received 0.09mg/kg of cladribine intravenously (2 hrs infusion) on days 1 to 5 and 375mg/m2 of rituximab intravenously on days 1 and 15, every 4 weeks, for a total of 4 cycles. Primary endpoint was overall response rate (ORR). Secondary endpoints were % complete response (%CR), 2 years progression free survival (2-y PFS), and 2 years overall survival (2-y OS). Results: A total of 20 out of 45 planned patients were enrolled and received R-2-CdA therapy from Apr 2005 to Jul 2007. Their median age was 58.5 (42–72), and the median number of prior regimens was 2 (1–3). Histologies included 16 follicular lymphomas, 2 MALT lymphomas, 1 nodal marginal B cell lymphoma, and 1 lymphoplasmacytic lymphoma. Fifteen pts (75%) were previously treated with rituximab. The ORR was 90% with 70% of % CR. Median PFS was 20.1 months (5.6–32.9 months) at a median follow-up time of 27 months. 2-y PFS and 2-y OS were 63.2% (95%CI, 28.1–67.8%), and 89.5% (95%CI, 69.8–97.2%), respectively. Severe neutropenia and thrombocytopenia of grade 3 or 4 were observed in 15% and 10% respectively. Conclusions: R-2CdA therapy was demonstrated to have high activity with durable PFS and acceptable toxicity in relapsed indolent B-NHL, even if patients were previously treated with rituximab. Although a large-scaled further trial remains to be needed, R-2-CdA therapy could be a good option of salvage therapy in relapsed indolent B-NHL. No significant financial relationships to disclose.

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Phase II Study of Oral Fludarabine Phosphate in Relapsed Indolent B-Cell Non-Hodgkin's Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.9313 ◽

2006 ◽

Vol 24 (1) ◽

pp. 174-180 ◽

Cited By ~ 30

Author(s):

Kensei Tobinai ◽

Takashi Watanabe ◽

Michinori Ogura ◽

Yasuo Morishima ◽

Yoshiaki Ogawa ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Hodgkin’S Lymphoma ◽

Response Rate ◽

Phase Ii Study ◽

Complete Response ◽

Hodgkin's Lymphoma ◽

Fludarabine Phosphate ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

Purpose Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkin's lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. Patients and Methods Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). Results Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. Conclusion Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

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