A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Bulky Stage II, Stage III or IV, Low-Grade B-Cell NHL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4709-4709
Author(s):  
Raul R. Mena ◽  
Neal P. Christiansen ◽  
Yudishtra Markan ◽  
Lalita Pandit
Keyword(s):  
B Cell ◽  
Stage Ii ◽  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Purine Analog ◽  
Grade 3 ◽  
Intent To Treat ◽  
Anti Cd20

Abstract The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody. P+C+R represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Eligibility criteria allow both treated and treatment-naïve patients diagnosed with Bulky Stage II or low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation was performed after cycles 2, 4, 6, 8 and 10 (if necessary). The intent-to-treat (ITT) population consisted of 76 NHL patients (median age 65, range 29–84) who received a total of 385 cycles (median 6 per patient). The ECOG status was 0 (64%), 1 (36%) and 2 (0%). The overall response rate (CR+Cru+PR) of the 69 evaluable patients was 72% (CR 11.6%, Cru 11.6%, PR 47.8%, SD 27.5% and PD or RD 1.4%). 12 grade 4 and 23 grade 3 neutropenias were documented. There were a total of 5 deaths due to acute myocardial infarction, NSCLC, a suspected cardiac event and 2 unknown cause of death. This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. The results will be updated at the meeting.

A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade B-cell non-Hodgkin lymphoma (NHL) or bulky stage II lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8071-8071
Author(s):  
N. P. Christiansen ◽  
R. Mena ◽  
Y. Markan ◽  
L. Pandit
Keyword(s):  
B Cell ◽  
Stage Ii ◽  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Non Hodgkin Lymphoma ◽  
Purine Analog ◽  
Treatment Naïve ◽  
Anti Cd20

8071 Background: The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological variations. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with these agents, pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation was performed after cycles 2, 4, 6 and 8 and 10 (if necessary). Results: The intent-to-treat (ITT) population consisted of 87 NHL patients (median age 62.5, range 29–84) who received a total of 476 cycles (median 6 per patient). The ECOG status was 0 (62.4%), 1 (37.6%) and 2 (0%). The overall response rate of the 80 evaluable patients was 72.5% (CR 11.3%, Cru 12.5%, PR 48.8%). 14 cases of grade 4 and 17 cases of grade 3 neutropenia were documented. There were a total of 4 deaths due to acute myocardial infarction, NSCLC, a suspected cardiac event and 1 unknown cause of death. Conclusions: This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Future trials evaluating the use of rituximab as maintenance therapy following this PCR regimen may also be warranted with a future goal towards possibly increasing the overall survival of patients with NHL. The presented results are preliminary and the study is currently on-going. No significant financial relationships to disclose.

A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade B-Cell NHL

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7591-7591
Author(s):  
R. R. Mena ◽  
N. P. Christiansen ◽  
D. W. Nyman ◽  
Y. Markan ◽  
N. M. Chowhan
Keyword(s):  
B Cell ◽  
Objective Response ◽  
Stage Iii ◽  
Second Primary ◽  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Purine Analog ◽  
Treatment Naïve ◽  
Anti Cd20

7591 Background: The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with these agents, pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation was performed after cycles 2, 4, 6 and 8. Patients were stratified by disease and by prior treatment status. Results: The intent-to-treat (ITT) population consisted of 54 NHL patients (median age 65, range 30–86) who received a total of 330 cycles (median 6 per patient). The ECOG status was 0 (31%), 1 (58%) and 2 (12%). The overall objective response rate was 71% (CR 15%, Cru 13%, PR 43%). Eight grade 4 neutropenias were documented along with a single grade 4 leukopenia. There were a total of 3 deaths which occurred within 30 days of the last dose. The first death was due to a second primary, NSCLC, diagnosed after treatment began. The second death occurred in an 81 year-old female, who had achieved PR, and her death was due to CHF. The last death, due to MI/CAD, occurred in an 84 year-old woman with SD. Conclusions: This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Updated trial results will be presented at the ASCO annual meeting. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. No significant financial relationships to disclose.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage III or IV, Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) or Bulky Stage II Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1354-1354
Author(s):  
Raul R. Mena ◽  
Neil P. Christiansen ◽  
Yudhishtra Markan ◽  
Lalita Pandit
Keyword(s):  
Febrile Neutropenia ◽  
B Cell ◽  
Single Agent ◽  
Stage Ii ◽  
Stage Iii ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade 3

Abstract The decision to treat indolent B-cell NHL is often based on progression of the disease. Most regimens have utilized fludarabine as the purine analog but the myelosuppression and immunosuppression of fludarabine combinations frequently results in severe infections. Combination therapy with pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, based on the single-agent activities, documented synergy, and non-overlapping toxicity profiles, may represent a promising approach in the treatment of these patients. To further investigate the efficacy of the PCR regimen for the treatment of indolent NHL, we conducted a phase II study. Patients diagnosed of bulky stage II, stage III/IV low-grade NHL (REAL classification), previously untreated or treated, were eligible. All patients were treated with intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for at least 8 cycles. 2 additional cycles were given for patients with PR or SD after cycle 8 or patients with CR/CRu first evident at cycle 8. Clinical evaluation was performed after cycles 2, 4, 6, 8, and 10 if necessary. Dose modification for hematologic toxicity may be increased to the previous higher level when a hematologic toxicity returned to normal. Two 25% dose reductions or one 50% dose reduction were allowed for nonhematologic toxicity. One hundred patients with indolent NHL, 68 previously untreated, 26 previously treated, and 6 with unknown treatment history, were enrolled in the study. The median age was 61 years (range 29–84) and 63.4% were ECOG PS 0, 36.6% PS1. A total of 550 cycles were given, with a median of 6 cycles per patient. 8 patients were not evaluated for response due to withdrawal of consent (n=1), unacceptable toxicities (n=3), and missing data (n=4). 92 patients received at least two cycles of treatment and were evaluated for response. The highest response rate (RR) achieved was 68%, with 10 (10%) CR, 12 (12%) CRu, 46 (46%) PR, 23 (23%) SD, and 1 (1%) disease progression. Stratified according to previous treatment status, patients with previously untreated NHL had an RR of 47% (CR, CRu 17%) while that of the previously treated was 17% (CR 7%). 14 (14.0%) patients discontinued treatment due to toxicities. Grade 3/ 4 hematological adverse events documented included 10 grade 4 and 16 grade 3 neutropenia. Infectious complications were noted in 8 patients including 3 grade 3 febrile neutropenia, 2 grade 4 febrile neutropenia, and 3 grade 3 infections. A total of 4 deaths were recorded, including 1 due to acute myocardial infarction, 1 suspected cardiac event and 2 unknown causes. This immunochemotherapeutic regimen is active in patients with indolent NHL. The study is currently on-going and updated results will be presented.

A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated stage III or IV, low-grade CLL

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6606-6606
Author(s):  
D. W. Nyman ◽  
R. Mena ◽  
R. Robles ◽  
M. Auerbach ◽  
L. Pandit
Keyword(s):  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Bulky Disease ◽  
Treatment Naïve ◽  
Acute Mi ◽  
Asco Meeting ◽  
Intent To Treat ◽  
Anti Cd20

6606 Background: The decision to treat indolent CLL is often based on progressive bulky disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are sensitive to combination immunochemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), a potent anti-CD20 monoclonal antibody. P+C+R represents a promising new approach in the treatment of patients with low grade CLL. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with low-grade stage III/IV CLL (modified Rai classification). Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation (including CT scan) was performed after cycles 2, 4, 6, and 8. Patients were stratified by disease and by prior treatment status. Results: The intent-to-treat (ITT) population consisted of 41 CLL patients (median age 64, range 36–85) who received a total of 207 cycles (median 4 per patient). ECOG status at enrollment was 0 (66%), 1 (27%) and 2 (7%). The overall response rate was 61% (CR 13%, PR 48%). One grade 4 neutropenia was documented. Four deaths have been recorded. An 81 YO patient was hospitalized 8 days after cycle 1; death, due to sepsis, occurred 22 days later. The death of an 83 YO was reported 10 days after cycle 2 as a result of an acute MI. An 83 YO patient, who developed gastroenteritis, was hospitalized 10 days after cycle 2. This progressed to dehydration and atrial flutter. Death came as a result of pulmonary edema and ASHD. An 82 YO man was hospitalized 4 days after completing cycle 2. He presented with extreme dyspnea but cause of death was CLL. Conclusions: This immunochemotherapeutic regimen is active in Grade III/IV CLL and the incidence of significant toxicities was low with deaths occurring only in elderly (>80 YO) patients. Updated results of this trial will be presented at the ASCO meeting. No significant financial relationships to disclose.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage II, III or IV CLL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4978-4978
Author(s):  
Raul R. Mena ◽  
Robert Robles ◽  
Michael Auerbach ◽  
Mehdi M. Moezi ◽  
David Headley
Keyword(s):  
Stage Ii ◽  
Open Label ◽  
Eligibility Criteria ◽  
Bulky Disease ◽  
Old Patients ◽  
Open Label Study ◽  
New Approach ◽  
Study Results ◽  
Intent To Treat ◽  
Anti Cd20

Abstract The decision to treat indolent CLL is often based on progressive bulky disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are sensitive to combination immunochemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody. P+C+R represents a promising new approach in the treatment of patients with CLL. Eligibility criteria allow both treated and treatment-naïve patients diagnosed with Stage II/III/IV CLL (modified Rai classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation (including CT scan) was performed after cycles 2, 4, 6, 8 and 10 (if necessary). The intent-to-treat (ITT) population consisted of 70 CLL patients (median age 64, range 35–83) who received a total of 286 cycles (median 4.5 per patient). ECOG status at enrollment was 0 (68%), 1 (28%) and 2 (4%). The overall response rate (CR+Cru+PR) of the 50 evaluable patients was 52% (CR 8%, Cru 14%, PR 30%, SD 46% and PD or RD 2%). 2 grade 4 neutropenia and 1 grade 4 respiratory distress was documented. 4 deaths have been recorded, all in elderly patients (>80 years old), due to acute respiratory failure, myocardial infarction, pulmonary edema and sepsis. This immunochemotherapeutic regimen is active in Stage II/III/IV CLL and the incidence of significant toxicities was low with deaths occurring only in elderly (>80 years old) patients. The study results will be updated at the meeting.

A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade CLL

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17508-17508
Author(s):  
R. R. Mena ◽  
R. Robles ◽  
M. Auerbach ◽  
M. Moezi ◽  
D. Headley
Keyword(s):  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Bulky Disease ◽  
Clinical Evaluations ◽  
Treatment Naïve ◽  
Grade Ii ◽  
Previously Treated ◽  
Intent To Treat ◽  
Anti Cd20

17508 Background: The decision to treat indolent CLL is often based on progressive bulky disease, worsening symptoms, and increasing hematological variations. When treatment is indicated, these lymphoproliferative disorders are sensitive to combination immunochemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody. PCR represents a promising new approach in the treatment of patients with low grade CLL. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with low-grade stage II/III/IV CLL (modified Rai classification). Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluations (including CT scan) were performed after cycles 2, 4, 6, 8, and 10 (if necessary). Results: The intent-to-treat (ITT) population consisted of 80 CLL patients (median age 64, range 35–83) who received a total of 368 cycles (median 5 per patient). ECOG status at enrollment was 0 (68.4%), 1 (27.6%) and 2 (3.9%). The overall response rate of the 59 evaluable patients was 61% (CR 6.8%, Cru 16.9%, PR 37.3%). 7 cases of grade 4 neutropenia, 2 cases of grade 4 respiratory distress, and 1 case of grade 4 anemia were reported. 5 deaths, all in elderly patients (>70 years old), have been recorded, due to acute respiratory failure, myocardial infarction, pulmonary edema, sepsis, and one unknown cause of death. Conclusions: This immunochemotherapeutic regimen is active in Grade II/III/IV CLL and the incidence of significant toxicities was low with deaths occurring only in elderly (>80 YO) patients. The presented results are preliminary and this study is currently on-going. No significant financial relationships to disclose.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated Bulky Stage II or Stage III or IV, Low-Grade B-Cell NHL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4750-4750
Author(s):  
Raul R. Mena ◽  
Neal P. Christiansen ◽  
David W. Nyman ◽  
Yudhishtra Markan ◽  
Naveed M. Chowhan
Keyword(s):  
Combination Therapy ◽  
B Cell ◽  
Stage Ii ◽  
Research Network ◽  
Stage Iii ◽  
Low Grade ◽  
Bulky Disease ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade Iii

Abstract Introduction: The decision to treat indolent B-cell NHL is often based on progressing bulky disease, worsening symptoms, and increasing hematologic derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with pentostatin (P), purine analog, cyclophosphamide (C), alkylator, and rituximab (R), anti-CD20 monoclonal antibody, represents a promising new approach in the treatment of patients with low grade NHL. Most regimens have utilized fludarabine as the purine analog, but the myelosuppression and immunosuppression of these combinations frequently results in severe infections. We have previously reported our experience with pentostatin and rituximab in a cohort of 133 previously treated and untreated patients with Grade III/IV NHL or CLL (2005 Pan-Pacific Lymphoma Conference). Methods: Fifty-five patients have been enrolled in this study with an expected accrual of 100. Patients are being enrolled through the Pharmatech Research Network. Eligibility criteria allows previously treated and treatment naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification). Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation was performed after even-numbered cycles. Patients were stratified by disease and by prior treatment status. Results: Forty-seven patients have been eligible for evaluation. NHL patients (median age 64, range 30–84) received a total of 236 cycles (median 6). The ECOG status was 0 (65%) and 1 (33%). The overall objective response rate was 70% (CR 21%, Cru 13%, PR 36%). There were 3 grade 4 neutropenias documented and there was a single grade 4 leukopenia. There were a total of 3 deaths all of which occurred within 30 days of the last dose. The first death was due to a second primary, NSCLC, diagnosed after treatment began. The second death occurred in a 81 year-old female (PR) due to CHF and the last death, due to CAD, occurred in an 84 year-old woman (SD). Conclusions: This immunochemotherapeutic regimen is very active in indolent Grade III/IV NHL and the incidence of significant toxities was extremely low. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. The use of combination therapy in elderly patients should be used with caution due to associated co-morbidities.

Phase I, Multicenter, Open Label, Dose Escalation of 90yttrium-Ibritumomab Tiuxetan Radioimmunotherapy Using a Modified Regimen for Relapsed or Refractory Follicular or Transformed CD20+ B-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1648-1648
Author(s):  
Christos Vaklavas ◽  
Ruby F Meredith ◽  
Susan J. Knox ◽  
Gregory Wiseman ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
B Cell ◽  
Dose Escalation ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Open Label ◽  
Complete Clearance ◽  
Grade 3

Abstract Abstract 1648 Introduction Radioimmunotherapy capitalizes on the radiosensitivity of non-Hodgkin lymphoma (NHL) and the targeted nature of monoclonal antibody therapy. In an attempt to reverse bone marrow infiltration with B-cells and, hence, optimize the biodistribution and tumor dosimetry of 90Y-ibritumomab tiuxetan, we conducted a multicenter, dose escalation, open label study to determine maximum tolerated dose (MTD), safety, and efficacy of a single course of 90Y-ibritumomab tiuxetan after four weekly doses of rituximab in relapsed or refractory low-grade or follicular or transformed CD20+ B-cell NHL. Methods A course of therapy included an initial dose of rituximab 250 mg/m2 plus 5 mCi of 111In- ibritumomab tiuxetan followed by three weekly doses of rituximab at 375 mg/m2 followed two weeks later by rituximab 250 mg/m2 plus 5 mCi of 111In-ibritumomab tiuxetan. Gamma camera imaging for dose estimates was conducted on days 1 and 36 following infusion of 111In- ibritumomab tiuxetan. If dose estimates were in the safe defined limits, and bone marrow on day 29 had less than 25% involvement by NHL, patients received on day 43 250 mg/m2 of rituximab plus a dose of 90Y-ibritumomab tiuxetan. Patients were scheduled to receive 90Y- ibritumomab tiuxetan in one of the dose escalation cohorts (0.4, 0.5, 0.6, 0.7 mCi/kg). Eligible patients were required to have histologically confirmed, relapsed or refractory low-grade or follicular or transformed B-cell NHL with demonstrable monoclonal CD20+ B-cell population in the lymph nodes or bone marrow. Patients with impaired bone marrow reserve, as indicated by prior myeloablative therapies with stem cell rescue, hypocellular marrow, history of failed stem cell collection or external beam radiation therapy to >25% of active bone marrow, and marked reduction in bone marrow precursors of one or more cell lines, were excluded. Results Cohort 1 (0.4 mCi/kg) enrolled 5 patients. Dose escalation was held after significant hematologic toxicity was observed in those patients (1 patient developed grade 4 and 3 grade 3 reversible thrombocytopenia, 4 patients developed grade 4 reversible leukopenia and neutropenia, and 1 patient developed grade 4 febrile neutropenia). One patient in this cohort did not receive the study drug due to the toxicity observed in the previous patients. The protocol was amended and 6 patients were enrolled at a lower dose cohort (0.3 mCi/kg); 1 patient experienced grade 4 neutropenia, whereas grade 3 leukopenia, neutropenia, and thrombocytopenia were seen in 2, 3, and 3 patients respectively. As the 0.3 mCi/kg dose was well tolerated, the 0.4 mCi/kg cohort was expanded to enroll 6 additional patients. In the expansion cohort, Grade 4 leukopenia and neutropenia were seen in 1 and 2 patients respectively; also, grade 3 leukopenia, neutropenia, and thrombocytopenia were seen in 3, 4, and 4 patients, respectively. All hematologic toxicities were reversible and no non-hematologic toxicities were seen with the exception of grade 1 fatigue in 2 patients. Among those who developed hematologic toxicities, the median duration of at least grade 3 leukopenia, neutropenia, and thrombocytopenia were 12 (range, 7–37), 10 (7–30), and 12 (3–44) days, respectively. Six patients had bone marrow involvement by NHL at registration ranging from <5% to 20%. Following 4 weekly doses of rituximab, marrow involvement decreased in all patients with complete clearance in 3 of them. In an intention-to-treat analysis, complete remission, partial remission, stable and progressive disease was achieved in 6 (35%), 8 (47%), 2 (12%), and 1(6%) patients, respectively (fig 1). With a median follow up of 31.7 months (range, 4.3 – 92.6 months), the median progression free survival (fig 2) and time to next treatment (fig 3) were 12.3 and 10.9 months, respectively. The median overall survival has not been reached. Conclusion The MTD of 90Y-ibritumomab tiuxetan administered to patients who have NHL marrow infiltration <25% following 4 weekly doses of rituximab was 0.4 mCi/kg. A 4 weekly course of rituximab decreased NHL marrow infiltration in all patients with marrow involvement and led to complete clearance in 50% of them. Although this regimen was associated with a high response rate, the hematologic toxicity was significant. Disclosures: No relevant conflicts of interest to declare.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage III or IV, Low-Grade CLL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5045-5045
Author(s):  
Raul R. Mena ◽  
Robert Robles ◽  
David W. Nyman ◽  
Michael Auerbach ◽  
Lalita Pandit
Keyword(s):  
Combination Therapy ◽  
Elderly Patients ◽  
Research Network ◽  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Bulky Disease ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade Iii

Abstract Introduction: The decision to treat indolent CLL is often based on progressing bulky disease, worsening symptoms, and increasing hematologic derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with pentostatin (P), purine analog, cyclophosphamide (C), alkylator, and rituximab (R), anti-CD20 monoclonal antibody, represents a promising new approach in the treatment of patients with low grade CLL. Most regimens have utilized fludarabine as the purine analog, but the myelosuppression and immunosuppression of these combinations and the disease of CLL frequently results in severe infections. We have previously reported our experience with pentostatin and rituximab in a cohort of 133 previously treated and untreated patients with Grade III/IV NHL or CLL (2005 Pan-Pacific Lymphoma Conference). Methods: Thirty-five patients have been enrolled in this study through the Pharmatech Research Network (64 sites). The expected accrual is 180 patients. Eligibility criteria allows previously treated and treatment naïve patients diagnosed with low-grade stage III/IV CLL (modified Rai classification). Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation (including CT scan) was performed after even-numbered cycles. Patients were stratified by disease and by prior treatment status. Results: CLL patients (median age 63, range 35–84) have received 138 cycles (median 5.5) so far. ECOG status at enrollment was 0 (80%) and 1 (14%). Overal response rate (N=29 evaluable) was 65% (CR 14%, CRu 7%, PRu 3%, PR 41%). One grade 4 neutropenia has been documented in this cohort. Five deaths have been recorded. One death occurred within 30 days of receiving chemotherapy. This patient (81 YO) was hospitalized 4 days after cycle 1 and death was due to sepsis and multi-organ failure occurred 18 days later. Another death (76 YO) was reported 30 days after cycle 1 due to pneumonia/respiratory insufficinency. An 84 YO patient had treatment delayed after cycle 2, she died at home of an apparent MI. An 83 YO man was hospitalized 2 weeks after completing cycle 2. This patient was dehydrated as a result of gastroenteritis however he developed atrial flutter and died as a result of pulmonary edema. The last patient discontinued therapy after achieving CRu following 3 cycles. Three months later she died of sepsis and pneumonia. Conclusions: This immunochemotherapeutic regimen is active in Grade III/IV CLL and the incidence of significant toxities was low with deaths occurring in elderly patients. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with CLL. The use of combination therapy in elderly patients should be used with caution due to associated co-morbidities.

Flavopiridol, fludarabine and rituximab (FFR) is an active regimen in indolent B-cell lymphoproliferative disorders and mantle cell lymphoma (MCL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7599-7599 ◽  
Author(s):  
T. S. Lin ◽  
B. Fischer ◽  
M. E. Moran ◽  
R. S. Shank ◽  
E. Kraut ◽  
...  
Keyword(s):  
B Cell ◽  
Kinase Inhibitor ◽  
Lymphocytic Leukemia ◽  
Stage Iii ◽  
Clinical Activity ◽  
Low Grade ◽  
Dose Escalation Study ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Cycle Growth ◽  
Grade 3

7599 Background: The cyclin-dependent kinase inhibitor flavopiridol is active in MCL and chronic lymphocytic leukemia (CLL) when given by 1-hr IV bolus dosing. Flavopiridol induces apoptosis independent of p53 and may eliminate tumor cells resistant to fludarabine and rituximab. Methods: We performed a phase I dose escalation study of flavopiridol, fludarabine and rituximab (FFR) in patients (pts) with MCL, CLL and indolent B-cell non-Hodgkin’s lymphoma (NHL). Pts received fludarabine 25 mg/m2 IV day 1–5 and rituximab 375 mg/m2 day 1 every 28 days for up to 6 cycles. Flavopiridol was given 50 mg/m2 by 1-hr IV bolus day 1 (cohort 1), day 1–2 (cohort 2), or day 1–3 (cohort 3) of each cycle. Growth factor support was prohibited. Results: Twenty-one pts were enrolled and are evaluable for toxicity and response. Median age was 62 years (range, 43–81); 8 pts had CLL, 5 MCL, 4 follicular NHL (FL), and 4 other low-grade NHL. Nine pts had received 1–2 prior therapies; 12 pts were previously untreated. CLL pts were Rai stage III/IV (5) or required treatment for stage I/II disease (3). NHL pts had stage III/IV (10) or progressive stage II disease (3). Dose limiting toxicity (DLT) was not observed in 3 pts in cohort 1. Two of 6 pts in cohort 2 developed DLT (grade 3 seizures; grade 3 renal failure due to nausea and diarrhea). Twelve additional pts were enrolled at the cohort 1 dose level, to define toxicity and efficacy. Pts received a median of 4 cycles (range 1–6), and 9 of 21 pts completed 6 cycles. Therapy was stopped early due to cytopenias (7), infection (2), DLT (2) or progressive disease (1). Response was graded by NCI 96 (CLL) or IWG (NHL) criteria. Overall response rate was 90%, and 14 pts achieved CR (67%). Six pts relapsed a median of 7.5 months (range 4–18) after finishing therapy; 13 pts remain in remission a median of 13.5 months (range 4–25) after therapy. All 9 MCL/FL pts responded (8 CR, 1 PR), and 8 pts remain in remission a median of 17 months (range 6–25) after therapy. Conclusions: FFR showed significant clinical activity in a small group of pts, but cytopenias limited therapy. We are currently studying a modified FFR regimen using a more active flavopiridol schedule (30-min IV bolus followed by 4-hr IV infusion) and allowing the use of prophylactic filgrastim. [Table: see text]

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