scholarly journals A randomized phase II trial comparing chemoimmunotherapy with or without bevacizumab in previously untreated patients with chronic lymphocytic leukemia

Oncotarget ◽  
2016 ◽  
Vol 7 (48) ◽  
pp. 78269-78280 ◽  
Author(s):  
Neil E. Kay ◽  
Paolo Strati ◽  
Betsy R. LaPlant ◽  
Jose F. Leis ◽  
Daniel Nikcevich ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Lymphocytic Leukemia ◽  
Randomized Phase Ii

Effects of motexafin gadolinium in a phase II trial in refractory chronic lymphocytic leukemia

2009 ◽  
Vol 50 (12) ◽  
pp. 1977-1982 ◽  
Author(s):  
Thomas S. Lin ◽  
Louie Naumovski ◽  
Philip S. Lecane ◽  
Margaret S. Lucas ◽  
Mollie E. Moran ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Lymphocytic Leukemia ◽  
Motexafin Gadolinium

NCRI CLL201 Trial: A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) with or without Rituximab in Previously Treated CLL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 752-752 ◽  
Author(s):  
Peter Hillmen ◽  
Christopher Pocock ◽  
Dena Cohen ◽  
Kim Cocks ◽  
Hazem A. Sayala ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Residual Disease ◽  
Early Death ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Color Flow ◽  
Randomized Phase Ii ◽  
Number Of Patients

Abstract Standard front-line therapy for chronic lymphocytic leukemia (CLL) is fludarabine plus cyclophosphamide. Adding mitoxantrone (FCM) or rituximab (FCR) appears to improve responses although no large randomized trials have been reported. We report a randomized Phase II trial of FCM and FCM-R in relapsed CLL. FCM was oral fludarabine (24mg/m2 for 5 days) and cyclophosphamide (150mg/m2 for 5 days) plus i.v. mitoxantrone (6mg/m2) on Day 1 of each cycle. FCM-R was identical with rituximab on Day 1 of each cycle (375mg/m2 cycle 1; 500mg/m2 cycles 2 to 6). Prophylaxis with aciclovir and co-trimoxazole was given. The primary end-point was response by NCI Criteria 2 months after therapy. Complete remission with incomplete marrow recovery (CR(i)) was defined according to the 2007 CLL Guidelines - clinical CR with a morphologically normal marrow but persistent cytopenias (i.e. platelets <100x109/l and/or neutrophils <1.5x109/l). In addition, minimal residual disease in the marrow was studied 2 months after therapy by four-color flow cytometry with MRD negativity defined as <0.01% CLL cells. 52 patients were entered into the trial with 26 in each arm. The median age was 65 (32–79) with 79% men. 42% had a β2m >4. The median number of prior therapies was 2 (1–6), 31 had prior fludarabine and 6 (12%) were refractory to or relapsed <6 months after fludarabine. 26/44 (59%) had unmutated VH genes (15/22 FCM-R; 11/22 FCM). 11 patients had deletion of 11q (FCM-R 5, FCM 6) and 1 patient had >20% 17p deleted cells (FCM-R). 36/52 (69%) received 4 or more cycles of therapy with no difference between FCM and FCM-R (18/26). Responses are shown in the Table. 35 SAE’s were reported in 23 patients. There was no difference in the number of patients with SAE’s between the arms (FCM 11, FCM-R 12). 6/7 patients (86%) who had 4 or more prior therapies reported an SAE, compared to 17/45 patients (38%) who had less than 4. 16 SAE’s were suspected to be related to FCM-R and 10 related to FCM. In summary, FCM-R is an effective therapy for relapsed CLL with over two-thirds of patients responding. The study design does not allow a statistical comparison between FCM and FCM-R but the results suggest that adding rituximab to FCM results in a higher complete response rate (CR + CR i = 43% for FCM-R and 13% for FCM) with more patients achieving MRD negativity (5 after FCM-R; 2 after FCM). The results of this randomised Phase II trial justify the study of FC with mitoxantrone and/or rituximab in larger randomized Phase III trials. Responses in 46 evaluable patients (remaining 6 not yet evaluable) All patients FCM FCM-R Number of patients 46 23 23 Overall response rate 29 (63%) 13 (57%) 16 (70%) CR 5 (11%) 1 (4%) 4 (17%) CR(i) 8 (17%) 2 (9%) 6 (26%) PR 16 (35%) 10 (43%) 6 (26%) SD/PD 12 (26%) 7 (30%) 5 (22%) Early Death (before assessment) 4 (9%) 2 (9%) 2 (9%) Withdrew consent (before assessment) 1 (2%) 1 (4%) 0 (0%) MRD negative 7 (15%) 2 (9%) 5 (22%)

Phase II trial of daily, oral green tea extract in patients with asymptomatic, Rai stage 0-II chronic lymphocytic leukemia (CLL).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 6522-6522
Author(s):  
T. D. Shanafelt ◽  
T. Call ◽  
C. S. Zent ◽  
B. LaPlant ◽  
J. F. Leis ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Green Tea ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Green Tea Extract ◽  
Lymphocytic Leukemia ◽  
Tea Extract

Phase II trial of recombinant leukocyte A interferon in patients with advanced chronic lymphocytic leukemia

1985 ◽  
Vol 78 (2) ◽  
pp. 216-220 ◽  
Author(s):  
Kenneth A. Foon ◽  
Gino C. Bottino ◽  
Paul G. Abrams ◽  
Mehmet F. Fer ◽  
Dan L. Longo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Lymphocytic Leukemia

Phase II Trial of Pulse Dosed Lenalidomide In Previously Treated Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1383-1383 ◽  
Author(s):  
Georg Aue ◽  
Susan Soto ◽  
Janet Valdez ◽  
Diane C Arthur ◽  
Xin Tian ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Lymphocytic Leukemia ◽  
Bulky Disease ◽  
Starting Dose ◽  
Duration Of Response

Abstract Abstract 1383 Introduction: Lenalidomide (L) has activity in relapsed chronic lymphocytic leukemia (CLL). The mechanism of action is not well understood but may involve stimulation of anti-leukemic immune responses. Myelosuppression especially neutropenia is a concerning side effect. We reasoned that pulsed dosing of lenalidomide could reduce myelosuppression while maintaining the immune stimulatory effect. To test this concept we initiated a single center, phase II trial (ClinicalTrials.gov Identifier: NCT00465127) of lenalidomide given in cycles of 3 weeks on, 3 weeks off drug (42 day cycles). Methods: Patients (pts) with relapsed CLL or small lymphocytic lymphoma with ANC>500/ul and platelets >20,000/ul were eligible. The primary endpoint defined as response after 4 cycles has been recorded for all participants. Pts with partial response were allowed to receive up to 4 additional cycles. The starting dose for the first 10 pts was 20 mg daily; the starting dose for pt 11 onwards was lowered to 10 mg daily because of toxicities observed in other L trials for CLL. TLS prophylaxis with Allopurinol was mandated during cycle 1–3. Deep venous thrombosis (DVT) prophylaxis was not mandated unless risk factors were present. Ibuprofen and corticosteroids were allowed to treat symptoms of a cytokine release syndrome (CRS, defined by LN swelling, fever, fatigue, pain, chills, dehydration). Responses were assessed by IWCLL criteria and included CT scanning. Patient characteristics (n=33) were: median age 64 years (36-78); median number of prior therapies 3 (range 1–7); 52% Rai stage III-IV; 70% bulky disease; 30% fludarabine refractory; 56% (of 27 pts) ZAP70 pos; 64% (of 25 pts) unmutated immune globulin VH mutation status; 43% del 17p; 15% del 11q. Results: A total of 131 cycles of L were given. 31 pts received at least 2 cycles of therapy (range 2–8) and were evaluable for response: 5 (16%) partial response (PR), 18 (58%) stable disease, and 8 (26%) progressive disease. 4 of 5 responding pts had del 17p and bulky disease. In responders (n=5, PR) vs non responders (n=26, SD+PD) the PFS was 16 vs 6 months (p>0.01), and the time to next therapy was 17 vs 6 months (p>0.01), respectively. Once treatment was stopped, duration of response was short lived (median 6 months, range 2–18). 4 out of 5 responders were observed in the 20 mg dose starting group versus only 1 responder in the 10 mg group (p=0.03). There was no difference in the CRS score between the 2 groups (2.5 vs 1.5, p=0.17). Hematologic responses were observed in 11 out of 24 CLL pts (45%). At the completion of 4 cycles CD4 and CD8 counts increased by 20%, while NK cell counts remained unchanged. Dose modifications/withdrawl: 41% of cycles required dose adjustments prior to or during cycles 1–4. 9 pts (27%) did not complete 4 cycles of L because of: autoimmune cytopenias (2 pts), side effects (4 pts; CRS 1 pt, neutropenia 3 pts), withdrawal from study (2 pts), and disease progression (1 pt). Toxicity: Gr 3/4 neutropenia was observed in 56% of 131 cycles, often worsening with cumulative cycles. Gr 3/4 thombocytopenia and anemia were seen in 30% and 15% of cycles, respectively. Gr 1/2 and 3/4 infections occurred in 23% and 11% of cycles, respectively, 8 of those in the setting of neutropenia. Gr 3 CMV colitis, PCP pneumonia and Candedemia each were observed once. 1 patient died from streptococcal sepsis in cycle 4. Gr 1/2 and 3/4 CRS were observed in 43% and 10% of cycles, respectively. A CRS was encountered in 78% of first cycles typically within the first week, and in 48%, 38% and 30% of cycles 2–4, respectively. 6 DVTs (Gr 3) were diagnosed in 5 pts. Other common side effects were fatigue (62%), rash (39%) and muscle cramps (27%), all Gr 1/2. No case of tumor lysis syndrome was seen. Conclusion: L cycled 3 weeks on, 3 weeks off led to stable disease in the majority of pts and induced PRs in 16% of relapsed CLL patients with high risk disease. Pulse dosing of L did not lead to reduced toxicities. Myelosuppression and infections remain a major concern. 4 out of 5 responders were observed in the 20 mg cohort arguing for higher L starting doses. Notably, side effects, particularly the CRS, were similar in the two cohorts. Once L was discontinued, the duration of response was short, suggesting a need for continued therapy in pts who are able to tolerate the drug. Disclosures: Off Label Use: Lenalidomide is not FDA approved in Chronic Lymphocytic leukemia.

Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B.

1989 ◽  
Vol 7 (4) ◽  
pp. 433-438 ◽  
Author(s):  
R O Dillman ◽  
R Mick ◽  
O R McIntyre
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Active Agent ◽  
Lymphocytic Leukemia ◽  
Prior Treatment ◽  
Eligibility Criteria ◽  
Group B ◽  
Leukemia Group

We conducted a phase II trial of deoxycoformycin (pentostatin [DCF]) in chronic lymphocytic leukemia (CLL). Eligibility criteria included age greater than 18 years, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, lymphocyte count greater than or equal to 15,000 cells/microL, international stage B or C disease (multiple lymph nodes involved and/or hemoglobin [Hgb] less than 11 g and/or platelets less than 100,000/microL) and no more than one prior treatment regimen. DCF dose was 4 mg/m2 intravenously (IV) weekly for 3 weeks and then every 2 weeks. There were 39 eligible patients (35 men and four women; median age, 63 years; median time from diagnosis to study entry, 3 years). Of these 39 patients, 31% were stage B and 33% had no prior treatment. Median laboratory values at entry were Hgb 10.5 g, WBC 96,100/microL, and platelets 93,500/microL. Nodal involvement was present in 90%, splenomegaly in 81%, and hepatomegaly in 47%. Patients received a median of nine DCF injections, with a range of four to 26. Three patients were not evaluable for response. Overall, 3% achieved a complete response (CR), 23% a partial response (PR), 28% showed clinical improvement (CI), and 38% had stable disease (SD). Associated toxicities (grade 2 or worse) observed were infections (52%), worsening of thrombocytopenia (26%) or anemia (33%), nausea and vomiting (31%), rash or pruritus (20%), and stomatitis (8%). We conclude that DCF is an active agent in CLL with acceptable toxicity.

Bendamustine Combined With Rituximab in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group

2011 ◽  
Vol 29 (26) ◽  
pp. 3559-3566 ◽  
Author(s):  
Kirsten Fischer ◽  
Paula Cramer ◽  
Raymonde Busch ◽  
Stephan Stilgenbauer ◽  
Jasmin Bahlo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Refractory Disease ◽  
Overall Response

Purpose The objective of this trial was to evaluate safety and efficacy of bendamustine combined with rituximab (BR) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL). Patients and Methods Seventy-eight patients, including 22 patients with fludarabine-refractory disease (28.2%) and 14 patients (17.9%) with deletion of 17p, received BR chemoimmunotherapy. Bendamustine was administered at a dose of 70 mg/m2 on days 1 and 2 combined with rituximab 375 mg/m2 on day 0 of the first course and 500 mg/m2 on day 1 during subsequent courses for up to six courses. Results On the basis of intent-to-treat analysis, the overall response rate was 59.0% (95% CI, 47.3% to 70.0%). Complete response, partial response, and nodular partial response were achieved in 9.0%, 47.4%, and 2.6% of patients, respectively. Overall response rate was 45.5% in fludarabine-refractory patients and 60.5% in fludarabine-sensitive patients. Among genetic subgroups, 92.3% of patients with del(11q), 100% with trisomy 12, 7.1% with del(17p), and 58.7% with unmutated IGHV status responded to treatment. After a median follow-up time of 24 months, the median event-free survival was 14.7 months. Severe infections occurred in 12.8% of patients. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia were documented in 23.1%, 28.2%, and 16.6% of patients, respectively. Conclusion Chemoimmunotherapy with BR is effective and safe in patients with relapsed CLL and has notable activity in fludarabine-refractory disease. Major but tolerable toxicities were myelosuppression and infections. These promising results encouraged us to initiate a further phase II trial evaluating the BR regimen in patients with previously untreated CLL.

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