A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma

Abstract Introduction: Mantle-cell lymphoma (MCL) is a type of B-cell non-Hodgkin lymphoma (NHL) that typically responds to initial chemo-immunotherapy, but with a relatively short duration of response (DR) and progression-free survival (PFS) when treated with conventional chemotherapy agents. Although the overall survival (OS) of MCL has improved, most patients are not cured and new agents are needed. A sub-analysis of a recent phase II trial (NHL-002) investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL, demonstrated a promising overall response rate (ORR) of 53% with a median DR of 11.9 months. A confirmatory international phase II trial (NHL-003) of single-agent lenalidomide was initiated for patients with relapsed/refractory aggressive NHL that had received at least one prior treatment and had measurable disease. In this report, we analyze the current results from the MCL patients enrolled in this trial. Methods: Patients with relapsed or refractory MCL and measurable disease ≥2 cm after at least 1 prior treatment regimen were eligible. Patients received 25 mg of lenalidomide orally once daily on days 1–21 of every 28-day cycle. Patients continued therapy until disease progression or toxicity. The 1999 IWLRC methodology was used to assess response and progression. Results: This report focuses on the 39 MCL patients that were enrolled and evaluable for response assessment. Median age was 66 (33–82) years and 29 (74%) patients were male. Median time from diagnosis to lenalidomide treatment was 3.4 (0.4–9) years. Patients had received a median of 3 (1–8) prior treatments, and 23% (9/39) of patients had received prior bortezomib treatment. The ORR with lenalidomide was 41% (16/39), including 13% (5/39) complete response (CR)/unconfirmed CR, and 28% (11/39) partial responses. Ten (26%) patients had stable disease. The most common grade 3 or 4 adverse events were neutropenia (51%) and thrombocytopenia (25%), anemia (13%), fatigue (10%) and febrile neutropenia (10%). Conclusion: These results confirm that lenalidomide oral monotherapy is effective in the treatment of patients with relapsed or refractory MCL, with manageable side effects.

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Phase II trial of single agent ofatumumab in relapsed/refractory mantle cell lymphoma

http://isrctn.org/> ◽

10.1186/isrctn32524443 ◽

2013 ◽

Author(s):

Sheila Bullard

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

Single Agent ◽

Mantle Cell

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Phase II trial and prediction of response of single agent tipifarnib in patients with relapsed/refractory mantle cell lymphoma: a Groupe d’Etude des Lymphomes de l’Adulte trial

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-009-1185-4 ◽

2009 ◽

Vol 65 (4) ◽

pp. 781-790 ◽

Cited By ~ 14

Author(s):

Delphine Rolland ◽

Vincent Ribrag ◽

Corinne Haioun ◽

Herve Ghesquieres ◽

Fabrice Jardin ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

Single Agent ◽

Prediction Of Response ◽

Mantle Cell

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COMBINATION OF IBRUTINIB WITH RITUXIMAB (IR) IS HIGHLY EFFECTIVE IN PREVIOUSLY UNTREATED ELDERLY (>65 YEARS) PATIENTS (PTS) WITH MANTLE CELL LYMPHOMA (MCL) - PHASE II TRIAL

Hematological Oncology ◽

10.1002/hon.11_2629 ◽

2019 ◽

Vol 37 ◽

pp. 42-42

Author(s):

P. Jain ◽

J. Romaguera ◽

K. Nomie ◽

S. Zhang ◽

L. Wang ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

Mantle Cell ◽

Highly Effective

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A multicentre phase II trial of gemcitabine for the treatment of patients with newly diagnosed, relapsed or chemotherapy resistant mantle cell lymphoma: SAKK 36/03

Hematological Oncology ◽

10.1002/hon.891 ◽

2009 ◽

Vol 27 (3) ◽

pp. 154-159 ◽

Cited By ~ 6

Author(s):

F. Hitz ◽

G. Martinelli ◽

E. Zucca ◽

R. von Moos ◽

W. Mingrone ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

Newly Diagnosed ◽

Multicentre Phase ◽

Mantle Cell

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Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS

Annals of Oncology ◽

10.1093/annonc/mdr450 ◽

2012 ◽

Vol 23 (6) ◽

pp. 1555-1561 ◽

Cited By ~ 32

Author(s):

R. Houot ◽

S. Le Gouill ◽

M. Ojeda Uribe ◽

C. Mounier ◽

S. Courby ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Mantle Cell

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Durable Responses with Bendamustine Monotherapy In Patients with Relapsed/Refractory Indolent B-Cell Non-Hodgkin Lymphoma (B-NHL) and Mantle-Cell Lymphoma (MCL): Updated Follow-up Data From a Japanese Multicenter Phase II Study

Blood ◽

10.1182/blood.v116.21.4884.4884 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4884-4884 ◽

Cited By ~ 1

Author(s):

Kuniaki Itoh ◽

Kiyoshi Ando ◽

Michinori Ogura ◽

Kenichi Ishizawa ◽

Takashi Watanabe ◽

...

Keyword(s):

B Cell ◽

Mantle Cell Lymphoma ◽

Phase Ii ◽

Group Performance ◽

Phase Ii Study ◽

Cell Lymphoma ◽

Multicenter Phase ◽

Short Period ◽

Mantle Cell

Abstract Abstract 4884 Background: Bendamustine is an alkylating agent with a unique mechanism of action and has demonstrated efficacy as a single agent for the treatment of relapsed or refractory indolent B-NHL or MCL. We conducted a multicenter, phase II study of bendamustine in Japanese patients with indolent B-cell NHL or MCL, reporting an overall response rate of 91% (90% in indolent B-NHL and 100% in MCL) according to International Workshop Response Criteria after a median follow-up of 12.6 months (Ohmachi et al. Cancer Sci 2010 [Epub ahead of print]). Here we report the updated progression-free survival (PFS) data, including median PFS, which had not been reached at the time of previous reports. Patients and Methods: Eligible patients (aged 20–75 years; Eastern Cooperative Oncology Group performance status of 0 or 1) with measurable, pathologically confirmed indolent B-NHL or MCL that failed to respond to, or relapsed after, prior therapy were enrolled. Bendamustine 120 mg/m2 was administered intravenously over 60 minutes on days 1 and 2 every 21 days for up to 6 cycles. PFS was assessed 3 months after completion of the last cycle, and then at 3-month intervals. Results: A total of 69 patients, aged 33–75 years, were enrolled: 58 with indolent B-NHL, mainly follicular lymphoma (n = 52), and 11 with MCL. Patients had primarily stage III or IV disease. The median number of prior regimens was 2 (range, 1–9) for patients with indolent B-NHL and 4 (range, 1–16) for those with MCL. A median of 5 (range, 1–6) bendamustine cycles were administered, with 72% of patients completing 3 or more cycles. The median follow-up time for all patients is 20.6 months (range, 2.5–27.2 months). The median PFS was 21.1 months (95% CI, 15.8-NA; NA = not available due to short period of observation): 20.0 months (95% CI, 12.3-NA) in indolent B-NHL, and 21.7 months (95% CI, 16.5-NA) in MCL. Estimated 2-year PFS rates were 45.2% and 34.1% in indolent B-NHL and MCL, respectively. Conclusions: Bendamustine monotherapy is highly effective in patients with relapsed or refractory indolent B-NHL and MCL. The durable responses observed in this study strongly support the use of bendamustine in these patients and are particularly encouraging in the relapsed or refractory MCL population. Disclosures: Off Label Use: Bendamustine is a novel alkylator that has shown efficacy and safety in patients with indolent lymphomas, and particularly encouraging is the activity in patients with mantle cell lymphoma, which is difficult to treat. Although bendamustine is currently investigational in Japan, approval for relapsed/refractory indolent NHL and mantle cell lymphoma is anticipated in October 2010.

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