Clinical trial of recombinant leukocyte A interferon as initial therapy for favorable histology non-Hodgkin's lymphomas and chronic lymphocytic leukemia. An Eastern Cooperative Oncology Group pilot study.

1986 ◽  
Vol 4 (2) ◽  
pp. 128-136 ◽  
Author(s):  
M J O'Connell ◽  
J P Colgan ◽  
M M Oken ◽  
R E Ritts ◽  
N E Kay ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Severe Toxicity ◽  
Favorable Histology ◽  
Initiation Of Therapy ◽  
Hodgkin's Lymphomas

Twenty patients with disseminated favorable histology non-Hodgkin's lymphomas (16 patients) or chronic lymphocytic leukemia (four patients) who had not received previous chemotherapy were treated with recombinant leukocyte A interferon (IFL-rA) (Hoffmann-La Roche, Nutley, NJ). Treatment was administered in a moderate dose (12 X 10(6) U/m2) by intramuscular (IM) injection three times weekly for 8 weeks, followed by weekly maintenance therapy for an additional 16 weeks in patients responding to therapy. Five patients with stable disease at 8 weeks received four additional weeks of three-times-weekly treatment at an escalated dose (25 X 10(6) U/m2). Interferon was tolerated without severe toxicity by most patients, although treatment was discontinued prematurely due to side effects in four patients. Objective tumor responses (one complete response [CR] and six partial responses [PRs]) were seen in seven of 16 patients with lymphoma (44%). One of four patients with chronic lymphocytic leukemia also experienced a PR. Median time-to-progression from initiation of therapy among responding patients was 26 + weeks (range, 7 + to 84 + weeks). This study has demonstrated single agent antitumor activity of IFL-rA given in a tolerable outpatient dosage regimen in patients with advanced favorable histology non-Hodgkin's lymphomas, and serves as a basis for further trials of IFL-rA combined with chemotherapy as initial therapy for such patients in the future.

Long-Term Follow-Up of Patients With Chronic Lymphocytic Leukemia (CLL) Receiving Fludarabine Regimens as Initial Therapy

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1165-1171 ◽  
Author(s):  
M.J. Keating ◽  
S. O’Brien ◽  
S. Lerner ◽  
C. Koller ◽  
M. Beran ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Response Rate ◽  
Single Agent ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Poor Correlation ◽  
American Society ◽  
Febrile Episodes

One hundred seventy-four patients with progressive or advanced chronic lymphocytic leukemia (CLL) have received initial therapy with fludarabine as a single agent or fludarabine combined with prednisone. The overall response rate was 78% and the median survival was 63 months. No difference in response rate or survival was noted in the 71 patients receiving fludarabine as a single agent compared with the 103 patients who received prednisone in addition. The median time to progression of responders was 31 months and the overall median survival was 74 months. Patients over the age of 70 years had shorter survivals. Patients with advanced stage disease (Rai III and IV) had a somewhat shorter survival than earlier stage patients. More than half the patients who relapsed after fludarabine therapy responded to salvage treatment, usually with fludarabine-based regimens. Second remissions were more common in patients who had achieved a complete remission on their initial treatment. The CD4 and CD8 T-lymphocyte subpopulations decreased to levels in the range of 150 to 200/μL after the first 3 courses of treatment. Although recovery towards normal levels was slow, the incidence of infections was low in patients in remission (1 episode of infection for every 3.33 patient years at risk) and decreased with time off treatment. There was no association of infections or febrile episodes with the use of corticosteroids or the CD4 count at the end of treatment and a poor correlation with the increase in CD4 counts during remission. Infectious episodes were less common in patients who had a complete response compared with partial responders. Richter’s transformation occurred in 9 patients and Hodgkin’s disease occurred in 4 patients. Five other patients died from other second malignancies. Fludarabine appears to be an effective initial induction therapy with a reasonable safety profile for patients with CLL. © 1998 by The American Society of Hematology.

Long-Term Follow-Up of Patients With Chronic Lymphocytic Leukemia (CLL) Receiving Fludarabine Regimens as Initial Therapy

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1165-1171 ◽  
Author(s):  
M.J. Keating ◽  
S. O’Brien ◽  
S. Lerner ◽  
C. Koller ◽  
M. Beran ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Survival ◽  
Response Rate ◽  
Single Agent ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Poor Correlation ◽  
American Society ◽  
Febrile Episodes

Abstract One hundred seventy-four patients with progressive or advanced chronic lymphocytic leukemia (CLL) have received initial therapy with fludarabine as a single agent or fludarabine combined with prednisone. The overall response rate was 78% and the median survival was 63 months. No difference in response rate or survival was noted in the 71 patients receiving fludarabine as a single agent compared with the 103 patients who received prednisone in addition. The median time to progression of responders was 31 months and the overall median survival was 74 months. Patients over the age of 70 years had shorter survivals. Patients with advanced stage disease (Rai III and IV) had a somewhat shorter survival than earlier stage patients. More than half the patients who relapsed after fludarabine therapy responded to salvage treatment, usually with fludarabine-based regimens. Second remissions were more common in patients who had achieved a complete remission on their initial treatment. The CD4 and CD8 T-lymphocyte subpopulations decreased to levels in the range of 150 to 200/μL after the first 3 courses of treatment. Although recovery towards normal levels was slow, the incidence of infections was low in patients in remission (1 episode of infection for every 3.33 patient years at risk) and decreased with time off treatment. There was no association of infections or febrile episodes with the use of corticosteroids or the CD4 count at the end of treatment and a poor correlation with the increase in CD4 counts during remission. Infectious episodes were less common in patients who had a complete response compared with partial responders. Richter’s transformation occurred in 9 patients and Hodgkin’s disease occurred in 4 patients. Five other patients died from other second malignancies. Fludarabine appears to be an effective initial induction therapy with a reasonable safety profile for patients with CLL. © 1998 by The American Society of Hematology.

Impact of Therapy With Chlorambucil, Fludarabine, or Fludarabine Plus Chlorambucil on Infections in Patients With Chronic Lymphocytic Leukemia: Intergroup Study Cancer and Leukemia Group B 9011

2001 ◽  
Vol 19 (16) ◽  
pp. 3611-3621 ◽  
Author(s):  
Vicki A. Morrison ◽  
Kanti R. Rai ◽  
Bercedis L. Peterson ◽  
Jonathan E. Kolitz ◽  
Laurence Elias ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Initial Therapy ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Best Response ◽  
Stage Disease ◽  
Group B ◽  
Leukemia Group

PURPOSE: We sought to determine whether therapy with single-agent fludarabine compared with chlorambucil alone or the combination of both agents had an impact on the incidence and spectrum of infections among a series of previously untreated patients with B-cell chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Five hundred fifty-four previously untreated CLL patients with intermediate/high-risk Rai-stage disease were enrolled onto an intergroup protocol. Patients were randomized to therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Data pertaining to infection were available on 518 patients. Differences in infections among treatment arms were tested with the Kruskal-Wallis, Wilcoxon, and χ2 tests. RESULTS: A total of 1,107 infections (241 major infections) occurred in 518 patients over the infection follow-up period (interval from study entry until either reinstitution of initial therapy, therapy with a second agent, or death). Patients treated with fludarabine plus chlorambucil had more infections than those receiving either single agent (P < .0001). Comparing the two single-agent arms, there were more infections on the fludarabine arm (P = .055) per month of follow-up. Fludarabine therapy was associated with more major infections and more herpesvirus infections compared with chlorambucil (P = .008 and P = .004, respectively). Rai stage and best response to therapy were not associated with infection. A low serum immunoglobulin G was associated with number of infections (P = .02). Age was associated with incidence of major infection in the combination arm (P = .004). CONCLUSION: Combination therapy with fludarabine plus chlorambucil resulted in significantly more infections than treatment with either single agent. Patients receiving single-agent fludarabine had more major infections and herpesvirus infections compared with chlorambucil-treated patients.

scholarly journals Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3489-3498 ◽  
Author(s):  
Xavier C. Badoux ◽  
Michael J. Keating ◽  
Sijin Wen ◽  
Bang-Ning Lee ◽  
Mariela Sivina ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Complete Response ◽  
Initial Therapy ◽  
Lymphocytic Leukemia ◽  
Common Grade ◽  
Grade 3

Abstract The best initial therapy for elderly patients with chronic lymphocytic leukemia (CLL) has not yet been defined. We investigated the activity of lenalidomide as initial therapy for elderly patients with CLL. Sixty patients with CLL 65 years of age and older received treatment with lenalidomide orally 5 mg daily for 56 days, then titrated up to 25 mg/d as tolerated. Treatment was continued until disease progression. At a median follow-up of 29 months, 53 patients (88%) are alive and 32 patients (53%) remain on therapy. Estimated 2-year progression-free survival is 60%. The overall response rate to lenalidomide therapy is 65%, including 10% complete response, 5% complete response with residual cytopenia, 7% nodular partial response, and 43% partial response. Neutropenia is the most common grade 3 or 4 treatment-related toxicity observed in 34% of treatment cycles. Major infections or neutropenic fever occurred in 13% of patients. Compared with baseline levels, we noted an increase in serum immunoglobulin levels across all classes, and a reduction in CCL3 and CCL4 plasma levels was noted in responding patients. Lenalidomide therapy was well tolerated and induced durable remissions in this population of elderly, symptomatic patients with CLL. This study was registered at www.clinicaltrials.gov as #NCT00535873.

Phase III Trial of Fludarabine Plus Cyclophosphamide Compared With Fludarabine for Patients With Previously Untreated Chronic Lymphocytic Leukemia: US Intergroup Trial E2997

2007 ◽  
Vol 25 (7) ◽  
pp. 793-798 ◽  
Author(s):  
Ian W. Flinn ◽  
Donna S. Neuberg ◽  
Michael R. Grever ◽  
Gordon W. Dewald ◽  
John M. Bennett ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Severe Thrombocytopenia ◽  
Severe Infections ◽  
Intergroup Trial

PurposeThe combination of fludarabine and cyclophosphamide is an effective regimen for patients with chronic lymphocytic leukemia (CLL). However, it may be accompanied by increased toxicity compared with fludarabine alone. E2997 is a phase III randomized Intergroup trial comparing fludarabine and cyclophosphamide (FC arm) versus fludarabine (F arm) alone in patients receiving their first chemotherapy regimen for CLL.Patients and MethodsSymptomatic, previously untreated patients with CLL were randomly assigned to receive either fludarabine 25 mg/m2intravenously (IV) days 1 through 5 or cyclophosphamide 600 mg/m2IV day 1 and fludarabine 20 mg/m2IV days 1 through 5. These cycles were repeated every 28 days for a maximum of six cycles.ResultsA total of 278 patients were randomly assigned in this Intergroup study. Treatment with fludarabine and cyclophosphamide was associated with a significantly higher complete response (CR) rate (23.4% v 4.6%; P < .001) and a higher overall response (OR) rate (74.3% v 59.5%, P = .013) than treatment with fludarabine as a single agent. Progression-free survival (PFS) was also superior in patients treated with fludarabine and cyclophosphamide than those treated with fludarabine (31.6 v 19.2 months, P < .0001). Fludarabine and cyclophosphamide caused additional hematologic toxicity, including more severe thrombocytopenia (P = .046), but it did not increase the number of severe infections (P = .812).ConclusionFludarabine and cyclophosphamide produced an increase in OR and CR, and it improved PFS in patients with previously untreated CLL compared with fludarabine alone and was not associated with an increase in infectious toxicity.

scholarly journals Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience

Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1910-1919 ◽  
Author(s):  
Susan O’Brien ◽  
Richard R. Furman ◽  
Steven Coutre ◽  
Ian W. Flinn ◽  
Jan A. Burger ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Key Points ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Over Time ◽  
Safety Signals

Key Points Our 5-year experience shows sustained single-agent efficacy of ibrutinib in CLL patients, with complete response rates increasing over time. Long-term ibrutinib was well tolerated with no new safety signals; rates of grade ≥3 cytopenias decreased with continued therapy.

Campath-1H and fludarabine in combination are highly active in refractory chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2245-2247 ◽  
Author(s):  
Ben Kennedy ◽  
Andy Rawstron ◽  
Chris Carter ◽  
Mary Ryan ◽  
Kevin Speed ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Chronic Lymphocytic Leukemia ◽  
Conventional Treatment ◽  
Single Agent ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Novel Therapy ◽  
Highly Active ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Campath-1H (alemtuzumab) is the most effective monoclonal antibody in single-agent use in B-cell chronic lymphocytic leukemia (CLL) with reported response rates of 33% to 70%. Combination therapy is now the conventional treatment for most hematologic malignancies. Monoclonal antibody treatments may sensitize tumor cells to subsequent chemotherapy. We report the combination of Campath-1H with fludarabine in patients with CLL refractory to each agent used singly. Six patients who had received a median of 8 courses of fludarabine (range, 4-10 courses) and 16 weeks of Campath-1H (range, 8-32 weeks) were treated. Five patients responded, including one who had a complete response by National Cancer Institute criteria. The responses observed were better in each patient than responses after each agent used singly. Complete morphologic bone marrow responses were seen in 3 patients, including eradication of disease measured by sensitive flow cytometry in 2. Campath-1H combined with fludarabine is a highly promising novel therapy for refractory CLL.

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