CULMINATE: A phase II study of cusatuzumab + azacitidine in patients with newly diagnosed AML, ineligible for intensive chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS7565-TPS7565 ◽  
Author(s):  
Geralyn Carol Trudel ◽  
Angela J. Howes ◽  
Neelum Jeste ◽  
Jeffrey J. Tryon ◽  
Liang Xiu ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Phase Ii Study ◽  
Standard Dose ◽  
Intensive Therapy ◽  
Moderate Hepatic Impairment ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Hematopoietic Stem

TPS7565 Background: AML, the most common acute leukemia in adults, is a heterogeneous malignancy characterized by uncontrolled clonal expansion of hematopoietic progenitor cells. Median diagnosis age is ~67 yrs. Despite current therapies prognosis is poor with 5-yr OS ~25% for patients (pts) ≥65 yrs. For pts unable to receive intensive chemotherapy, survival rates are worse, indicating a critical need to develop better treatments. CD70 is expressed on >95% of AML blasts harvested from newly diagnosed AML pts but not on normal hematopoietic stem cells nor most normal tissues. Cusatuzumab is a first-in-class, high-affinity anti-CD70 monoclonal antibody with multiple mechanisms of action, including Fc-mediated cytotoxicity with enhanced ADCC and inhibition of CD70/CD27 signaling, resulting in leukemia blast and stem cell cytotoxicity. As cusatuzumab and azacitidine target distinct pathways of myeloblast propagation, a combination may have a synergistic therapeutic effect and overcome treatment resistance. Initial data from a Phase I study (NCT03030612) with cusatuzumab (1–20 mg/kg) + standard dose azacitidine in AML pts ineligible for intensive chemotherapy showed no dose-limiting toxicity and a CR/CRi (CR with partial/incomplete hematologic recovery) in 10 of 12 pts (ASH 2019, Abs #234). This abstract describes a follow-on Phase II study (NCT04023526). Methods: CULMINATE is a 2-part study of cusatuzumab + azacitidine to determine the optimal dose of cusatuzumab (Table). Inclusion criteria: ≥18 yrs with de novo or secondary AML unfit for intensive therapy (≥75 or <75 yrs with a comorbidity [i.e. ≥1 of: ECOG 2, severe cardiac/pulmonary or moderate hepatic impairment]). In Part 1, pts are randomized 1:1 to cusatuzumab 10 or 20 mg/kg (IV, on Days 3 and 17 of each 28-day cycle) + azacitidine (75 mg/m2 SC or IV on Days 1–7). Data will be reviewed after 15, 30 and 50 pts are enrolled into each arm to select the cusatuzumab dose for the Part 2 expansion cohort in which efficacy and safety will be further evaluated. Follow-up continues until death, loss to follow-up or study end. The primary objective is to determine CR rate. Secondary objectives include rate of CRi/CRh, rate of MRD-negativity, ORR, time to and duration of response, pharmacokinetics, immunogenicity, transfusion independence and safety. Enrollment began in Sept 2019 and is currently two-thirds complete. Clinical trial information: NCT04023526 . [Table: see text]

A Phase II Study of Intravenous Azacitidine Alone in Patients with Myelodysplastic Syndromes NCT00384956.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1451-1451
Author(s):  
Richard Walgren ◽  
Crystal Dao ◽  
Frederieke Kreisel ◽  
Peter Westervelt ◽  
Camille Abboud ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
De Novo ◽  
Phase Ii Study ◽  
Study Drug ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Open Label ◽  
Erythroid Response

Abstract Rationale: 5-Azacytidine (Aza), a DNA hypomethylating agent, has now been shown in 2 clinical trials involving high-risk MDS patients to provide a survival benefit over supportive/conventional care regimens. While one phase II study used a continuous 7-day IV infusion, Aza was administered subcutaneously (SQ) in most pre-approval studies. However, injection site reactions are not uncommon with SQ dosing, especially in thrombocytopenic patients. Aza given as a short intravenous (IV) infusion is anticipated to be efficacious from pharmacokinetic profiling and is FDA approved, but prospective efficacy data for short IV infusion are lacking. Study aim and design: To determine the efficacy of IV Aza when given as a short infusion, we have undertaken an open-label, single-arm, single-center phase II study of Aza in patients with MDS, either de novo or secondary, defined by FAB classification. Previously treated subjects were ineligible if they had already received Aza or decitabine. Treatment consisted of Aza 75 mg/m2 given as a 20 minute IV infusion once daily on Days 1–5 of a 28-day cycle. Response was evaluated by IWG 2000 criteria. After two cycles at the 75 mg/m2 dose, patients failing to achieve a CR were eligible for an increased dose of 100 mg/m2. After 6 cycles of therapy, patients must have demonstrated at least a hematologic improvement to continue on study. Study endpoints include determination of the complete response (CR) and partial response (PR) rates, and secondary endpoints examined the rates of hematological improvement, time to progression, and cytogenetic response. Results: Accrual began 8/17/06 with a target of 21 subjects. As of 7/31/07, 15 subjects have accrued with a median follow-up of 77 days (range 4 to 246). Subjects consisted of 9 males and 6 females with a median age of 69.6 yr (range 53 to 82). The median time from diagnosis is 213 days (range 0 days to 4 yr). By FAB criteria, subjects consist of 4 RA, 9 RAEB, 1 RAEB-t, and 1 CMML, and subjects are categorized by IPSS risk as 1 Low, 4 Int-1, and 10 Int-2. Two patients had therapy related MDS. The data remain preliminary with subjects having completed a mean of 3 cycles (range 1 to 6). None of the 5 subjects who have completed at least 4 cycles of therapy have achieved a CR. However, 2 (40%) of these subjects achieved a PR. Additionally, 1 (20%) patient had a major erythroid response, while another had a minor erythroid response. Median time to response was 2 months. Ten subjects remain on study, 1 patient withdrew due to progressive disease (in first week of therapy), and 4 deaths have occurred on study (2 due to sepsis, 1 each due to pneumonia and acute MI). No deaths were attributed to study drug. Common adverse events include nausea, emesis, and hematologic toxicities. Grade 2–3 nausea and grade 2–3 emesis each occurred in 5 subjects. Observed grade 3 or 4 hematologic toxicities included: anemia (n=7), thrombocytopenia (n=4), leukopenia (n=3), neutropenia (n=7), and febrile neutropenia (n=1). Hematologic toxicities have resulted in transient treatment delays (&lt; 4 weeks) and dose reduction, but hematologic toxicities have not prevented subsequent treatment on study. Conclusions: Although follow-up is short for assessment of efficacy, this is the first prospective study to report on efficacy and toxicity of short infusional Aza in the treatment of MDS.

High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed BCR-ABL–Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group

2006 ◽  
Vol 24 (3) ◽  
pp. 460-466 ◽  
Author(s):  
Masamitsu Yanada ◽  
Jin Takeuchi ◽  
Isamu Sugiura ◽  
Hideki Akiyama ◽  
Noriko Usui ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Severe Toxicity ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Short Period

Purpose A novel therapeutic approach is urgently needed for BCR-ABL–positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib. Patients and Methods A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL–positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005. Results Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not. Conclusion Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL–positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.

Phase II Study of Sphingosomal Vincristine in CHOP+/ − Rituximab for Patients with Aggressive Non-Hodgkin’s Lymphoma (NHL): Promising 3 Year Follow-Up Results in Elderly Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 943-943
Author(s):  
Maria Alma Rodriguez ◽  
Nam H. Dang ◽  
Luis Fayad ◽  
Andre Goy ◽  
Fredrick Hagemeister ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Standard Dose ◽  
Age Groups ◽  
B Cell Lymphoma ◽  
Younger Patients

Abstract Background: Individuals older than 60 years have a worse prognosis than younger patients with aggressive NHL. Vincristine is an active drug in the treatment of malignant lymphomas. Sphingosomal vincristine (SV) was well tolerated with 45% ORR in patients with multiple relapses of aggressive NHL (ASH abst. 412, 1999). Based on these data, a phase II study of CHOP with rituximab (no rituximab for T-cell histology), and substituting SV for free vincristine, was undertaken in patients with previously untreated aggressive NHL. Methods: Aggressive NHL histologies eligible for study were diffuse large B-cell lymphoma (DLCL), peripheral T-cell lymphoma (PTCL), follicular lymphoma grade 3 (FL gr3), anaplastic large cell lymphoma (ALCL), and indolent lymphomas with aggressive transformation (TL). Patients were treated with standard dose CHOP that included SV 2.0 mg/m2 without dose capping, ± rituximab 375 mg/m2, given every 21 days for 6 to 8 courses (ASH abst. 338, 2002). Results: Of 73 patients enrolled on study, 68 were evaluable for response. Median age was 61 (range 22–80), 36 patients (53%) were &gt;60 years old. Overall, 24 patients (23 elderly) had an IPI score ≥3. Patients received a median of 6 study treatments (range 1–8). Diagnoses were: DLCL = 56; FL gr 3 = 4; PTCL = 4; ALCL = 2 and TL = 2. ORR was 92.6% (63/68 pts) with 55 pts achieving CR (80.1%), 7 CRu (10.3%), and 1 PR (1.5%); 3 patients had PD (4.4%) and 2 were not assessed for response (2.9%). ORR was similar in both elderly (&gt;60) and younger pts (≤60): 91.9% and 93.5% respectively. Neuropathy was generally mild (Gr.1–2). Hematological toxicities were as follows: 56% Gr.3–4 neutropenia, 6% Gr.3 anemia, and 13% Gr.3–4 thrombocytopenia. Toxicites were comparable in elderly and younger patients. The median follow up for the study is 39.6 months (mos), and overall survival 94%. There have been 9 relapses (5 DLCL, 3 T-cell, 1 FL gr3, 1 transformed) for elderly patients and 5 relapses (4 DLCL, 1 T-cell) for patients ≤60. The table below shows progression free survival (PFS) at 3 years, for all histologies, and DLCL by age. There is no difference between the age groups. Conclusions: This regimen, with sphingosomal vincristine in CHOP +/− Rituximab, has a high overall response rate. It is a well-tolerated therapy with mild neurotoxicity for all patients. At 3 years, the PFS in elderly patients with DLCL treated with RCHOP is comparable to that of younger patients, despite a larger fraction of high risk IPI in the older patients. This regimen merits randomized comparison to RCHOP in DLCL. Age (Yrs) All Histologies (n=68) DLCL (n=56) ≤60 84%, CI [66–93] 85%, CI [66–94] &gt;60 83%, CI [66–92] 86%, CI [66–94]

A Prospective Phase II Study on Tandem Autografting-Nonmyeloablative Allografting for Newly Diagnosed Myeloma: Final Results of the Gruppo Italiano Trapianto Midollo Osseo.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3026-3026
Author(s):  
B. Bruno ◽  
M. Rotta ◽  
F. Patriarca ◽  
D. Mattei ◽  
B. Allione ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Chronic Gvhd ◽  
New Drugs ◽  
Newly Diagnosed ◽  
Disease Response ◽  
Post Transplant ◽  
Primary Endpoints ◽  
Prospective Phase

Abstract The development of nonmyeloablative conditionings has recently reduced the transplant-related mortality (TRM) and extended the eligible age for transplantation up to 65–70 years. From January 2000 to June 2005, 106 newly diagnosed patients younger than 65 years were enrolled in a prospective phase II study at 15 Italian Centers. Fifty-eight were also previously described in a comparison of autografting with allografting based on a genetic randomisation (Bruno et al. N Engl J Med 2007). Here we report on a larger GITMO experience with a longer follow-up. Induction chemotherapy consisted of VAD-based regimens, followed by a cytoreductive autograft with melphalan 200 mg/m2, and by a non-myeloablative 2 Gy TBI-based allograft from an HLA-identical sibling. Graft-vs-host disease (GVHD) prophylaxis included cyclosporin and mycophenolate mofetil. Primary endpoints were overall (OS) and event-free (EFS) survivals. Secondary endpoint was TRM. One-hundred-two (96%) patients, median age 54 (30–65), completed the tandem program whereas 4 withdrew their consent. After a median follow-up of 54 (21–94) months, OS was not reached and median EFS was 35 (31–56) months post-transplant. Incidences of acute grade II-IV GHVD and extensive chronic GVHD were 40% and 50% respectively. Fourteen (13%) patients died from TRM, 14 (13%) from disease progression, 2 from lung cancer (2%) and 1 from lymphoma (1%). Overall response, defined as complete (CR) and partial remission, was 91% (93/102), with 53 patients achieving CR. Overall 39/102 patients relapsed, however only 8/53 of those who reached CR post-transplant. By multivariate-analysis disease response prior to allografting was significantly associated with longer OS (HR 0.27, CI 0.09–0.80, p<0.018) and longer EFS (HR 0.23, CI 0.11–0.49, p<0.001). Interestingly, chronic GVHD was not correlated with either the achievement of post-transplant CR (HR 0.87, CI 0.45–1.65, p<0.66) or its duration (HR 0.79, CI 0.45–1.40, p<0.42). Presence of del(13) was evaluated only in a subset of 39 patients: 13 carried del(13) and 26 did not. OS was not reached in the patients without del(13) and was 52 months in patients with del(13) (p=0.32), however EFS was not reached in the patients without del(13) whereas was 27 months for patients with del(13) (p=0.04). Given the encouraging results, the design of prospective studies that incorporate new drugs to cytoreduce the disease pre-transplant and enhance graft-vs.-myeloma are warranted to lower relapse rates and improve clinical outcomes.

A phase II study of voreloxin as single agent therapy for elderly patients (pts) with newly diagnosed acute myeloid leukemia (AML)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7048-7048
Author(s):  
M. B. Maris ◽  
F. Ravandi ◽  
R. Stuart ◽  
R. Stone ◽  
L. Cripe ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Phase Ii Study ◽  
Ex Vivo ◽  
Single Agent ◽  
Clinical Activity ◽  
Newly Diagnosed ◽  
Elderly Age ◽  
Secondary Aml ◽  
Early Results

7048 Background: Voreloxin is a naphthyridine analog that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Interim results of REVEAL-1, a phase II study of single agent voreloxin in newly diagnosed elderly AML pts, are reported. Methods: Phase II study of 3 voreloxin schedules (approximately 30 pts/schedule): A) 72 mg/m2qw x 3; B) 72 mg/m2qw X 2; or C) 72 mg/m2/dose on D1 and D4. Eligibility: newly diagnosed AML (de novo or secondary AML), pts age ≥ 60 and ≥ 1 additional adverse risk factor (age ≥ 70, secondary AML, intermediate or unfavorable cytogenetics, or PS 2). PK were evaluated in a pt subset in cycle 1. ex vivo sensitivity of pt BMA to voreloxin was evaluated by CellTiter-Glo proliferation assay. Results: Enrollment targets for schedules: A) (29) and B) (31) are met. Demographics (N = 54): 66% male, 35% female; median age 75 years; ECOG PS 0–1 90%, PS 2 10%. 20% AHD and cytogenetics were intermediate in 29%, unfavorable in 34%, and unknown in 36%. Final CR + CRp rate: A) 38%; B) too early to evaluate. Median duration of remission has not been reached. Thirty day all-cause mortality: A) 17%; B) 1 of 22, 4.5%. Infection was the most common cause of early mortality. Tolerability improved markedly in B): G3 or higher pneumonia (A 24%, B 11%) and mucositis (A 21%, B 11%) incidence were reduced. Voreloxin PK were similar to those in an earlier single agent phase I study in relapsed/refractory AML. C) enrollment is pending. Ex-vivo sensitivity did not predict clinical response. Conclusions: In REVEAL-1, voreloxin demonstrates clinical activity with 2 dosing schedules in previously untreated elderly (age ≥ 60) patients with AML who are unlikely to benefit from standard chemotherapy. CR + CRp rate was 38% (11 of 29 pts) for 3 weekly voreloxin doses (A). Early results from 2 weekly voreloxin doses (B) show 6 CR + CRp of 21 evaluable pts, with 2 pts in heme recovery, and improved tolerability. Enrollment to (C), voreloxin dosed D1 and D4, is pending. [Table: see text]

scholarly journals A Phase II Study of Bortezomib-GIFOX (Gemcitabine, Ifosfamide, Oxaliplatin) in Patients with Newly Diagnosed Natural-Killer/T-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5353-5353 ◽  
Author(s):  
Tiffany Tang ◽  
Kevin Tay ◽  
Miriam Tao ◽  
Richard Hong Hui Quek ◽  
Mohamad Farid ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Stage Ii ◽  
Newly Diagnosed ◽  
Natural Killer T Cell ◽  
Killer T Cell

Abstract Background: Natural-killer/T-cell lymphoma (NKTL) is a subtype of non-Hodgkin's lymphoma with poor response to conventional chemotherapy. Gene expression profiling of NKTL revealed overexpression of NF-kB. Bortezomib (B) is a potent and reversible proteasome inhibitor which has shown single agent activity in preclinical models of NKTL in vitro and in vivo. Further, drug testing in mouse NKTL xenograft suggest gemcitabine (G), oxaliplatin (ox) and ifosfamide (if) were effective in inducing tumor regression. We have also previously published a patient with relapsed NKTL that was successfully treated with GIFOX therapy. Hence we conducted a study to evaluate the clinical efficacy of B-GIFOX in patients with newly diagnosed NKTL. Methods: This was an open-labelled prospective phase II study approved by the institutional review board. Patients with histologically confirmed NKTL with stage IB or bulky(X) and stage II-IV disease were included. Patients with stage IB/IX or II were treated with 4 cycles of B-GIFOX followed by radiotherapy. Patients with advanced stage disease were treated with 6 cycles of B-GIFOX. Intravenous B was dosed at 1.3mg/m2 on days 1, 4, 8, and 11 every 21 days. Dose and schedule of G, If and Ox were 1000mg/m2 on day 1, 5g/m2 on day 2 and 85mg/m2 on day 2 respectively. The primary objective was to estimate the overall response rates (ORR) and the secondary objectives were to estimate the progression free survival (PFS), overall survival (OS) and toxicities of this regimen. PFS was calculated from the start of treatment to the date of progression or last follow-up. OS was calculated from the start of treatment to the date of death or last follow-up. Both median PFS and OS were estimated using Kaplan-meier curves. Results: There were 7 patients recruited into the study; 3 had stage II disease and 4 had stage IV disease. The median age was 50 years (range: 34-61) and 5 (71.4%) were male. Four patients had B symptoms and all but one patient had elevated LDH at diagnosis. Six patients completed their planned treatment and one patient had disease progression through the first cycle of chemotherapy. The ORR was 42.8%; one patient had a complete response, two had partial responses and 4 had progressive disease. The median PFS was 4.3months (95% confidence interval [CI] 4.0-4.6 months) and the median OS was 14.9months (95% CI 0.6-29.2 months). The following grade 1-2 toxicities were seen in at least 1 patient: anemia (7), thrombocytopenia (5), fever (3), ALT increase (3), nausea (2), vomiting (2), ALP increase (2), AST increase (1), alopecia (1), fatigue (1), and body ache (1). The following grade 3-4 toxicities were seen in at least 1 patient: thrombocytopenia (2), and tumor lysis syndrome (1). Conclusion: This study showed that B-GIFOX induced an ORR of 43% in patients with newly diagnosed NKTL however the median PFS was short at around 4months. Disclosures No relevant conflicts of interest to declare.

scholarly journals Epigenetic Priming Using Decitabine Followed By Cytarabine As an Induction Regimen in Older Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2265-2265
Author(s):  
Annie Im ◽  
Jing-Zhou Hou ◽  
Anastasios Raptis ◽  
Mounzer Agha ◽  
Rafic Farah ◽  
...  
Keyword(s):  
Older Adults ◽  
Phase Ii ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Phase Ii Study ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Induction Regimen ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background: Acute myeloid leukemia (AML) in older patients is associated with a poor prognosis, with lower complete remission (CR) rates and worse overall survival compared to younger patients. Moreover, most older patients over the age of 70 years do not tolerate standard induction chemotherapy. Alternative therapy with hypomethylating agents can improve CR rates and survival compared to best supportive care, but overall outcomes remain poor after current therapeutic options in this patient population. Preclinical studies suggest that “epigenetic priming” using decitabine followed by cytarabine increases the cytotoxicity of cytarabine. It is hypothesized that this is due to the reactivation of genes that have been silenced by the malignancy. The aim of this phase II study is to evaluate the efficacy and safety of a novel induction regimen using decitabine followed by cytarabine in older patients with newly diagnosed AML who are not candidates for intensive chemotherapy. Here we present response rates and treatment-related mortality for the first 23 evaluable subjects. Methods: A phase II, single arm study of decitabine and cytarabine is ongoing at the University of Pittsburgh Cancer Institute (NCT 01829503) for patients over the age of 70 years with newly diagnosed AML, or patients over the age of 60 years who are considered not to be candidates for intensive chemotherapy. The induction regimen consists of decitabine 20mg/m² intravenously (IV) x 5 days followed by standard dose cytarabine 100mg/m² continuous IV infusion x 5 days. Patients with no evidence of disease on day 15 bone marrow biopsy proceed with maintenance decitabine. Patients with persistent disease but no evidence of progression proceed with a second cycle of induction using the same regimen. Patients with progressive disease after 1 cycle are taken off study. After a second induction cycle, patients with no evidence of disease, or persistent disease but no evidence of progression, proceed with maintenance decitabine. Maintenance cycles consist of decitabine 20mg/m² IV x 5 days every 4-8 weeks until disease progression. Response rates are evaluated by the International Working Group Response Criteria in AML. Treatment-related mortality is defined at mortality within 8 weeks of initiation of induction therapy. Results: Twenty-five subjects of a planned 37 subjects have been enrolled as of August 2014, 23 of whom were evaluable for response at the time of analysis. At the time of this preliminary analysis, the median age was 76 years (range 68-82 years). There are 11 females (44%) and 14 males (56%). The median ECOG performance status was 1 (range 0-2). There were 14 patients with poor risk cytogenetics at diagnosis. Of the 23 patients who are evaluable for response, there were 14 (61%) patients with a CR and 2 patients with a CRi (CR+CRi rate 70%). Two patients had a partial remission, 1 patient had a morphologic leukemia free state, and 4 patients had resistant disease. All patients except for 2 received 2 cycles of induction. Of the 14 patients who had poor risk cytogenetics at diagnosis, 10 (71%) had a CR, and 8 had normalization of their previous cytogenetic abnormalities. There have been no treatment-related mortalities to date. Conclusion: We have shown that an induction regimen using decitabine as an epigenetic primer followed by cytarabine induces high CR+CRi rates with no treatment-related mortality in older adults with newly diagnosed AML who are not candidates for intensive chemotherapy, a patient population in whom there exists a dire need for novel treatment strategies. In the first report of this phase II study, 70% of patients achieved a CR or CRi, and there were no treatment related mortalities. This compares favorably with historical outcomes of both intensive chemotherapy and decitabine monotherapy in older adults in terms of safety and efficacy, respectively. Final analysis of this clinical trial will include overall survival analysis, rate of grade III and IV adverse events, and epigenetic correlative studies. We have demonstrated that decitabine followed by cytarabine is a safe and effective regimen in older adults with newly diagnosed AML. Disclosures No relevant conflicts of interest to declare.

Durable Event-Free and Overall Survival (EFS/OS) in Mantle Cell Lymphoma (MCL) without Rituximab: Long-Term Follow-Up of a Phase II Trial with Intensive Chemotherapy (CTAP/VMAC) Followed by Autologous Hematopoietic Stem Cell Transplant (aHSCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2448-2448
Author(s):  
Andrew M. Evens ◽  
Jane N. Winter ◽  
Nanjiang Hou ◽  
Fred Rademaker ◽  
Katalin Kelemen ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Survival Rates ◽  
Interleukin 2 ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Hematopoietic Stem

Abstract MCL is associated with high relapse rates and poor survival when treated with standard chemotherapy (chemoTx). We report long-term outcomes with intent-to-treat (ITT) analysis of a prospective phase II protocol of intensive induction chemoTx, followed by HSCT in first complete or partial remission (CR/PR). MCL diagnosis was based on histology with cyclin D1+ or CCND1/IGH fusion. Induction chemoTx consisted of cyclophosphamide 1.5 gm/m2, teniposide 100 mg/m2, and doxorubicin 50 mg/m2 all given day 1 and prednisone 100 mg/m2 days 1–5 (CTAP); this was followed by vincristine 1.4 mg/m2 and methotrexate 3.0 gm/m2 on day 21 and cytarabine 3.0 gm/m2 × 2 doses 12 hours apart day 22 (VMAC). Patients (pts) who achieved CR/PR after 2 cycles CTAP/VMAC (1 cycle=42 days) received 1 additional cycle. Pts ≤ age 65 then proceeded to aHSCT, while pts < 50 with a matched sibling donor had allogeneic HSCT, both with busulfan/cyclophosphamide200 conditioning. After aHSCT, pts received maintenance αinterferon/interleukin-2 (αIFN/IL-2) given together QD Monday-Friday every other month (mos) × 3 mos (both dosed at 3×106 IU/m2). Responding pts > age 65 proceeded directly to αIFN/IL-2 after 3 cycles chemoTx. 25 newly diagnosed MCL pts were entered onto trial from 2/97 through 11/02. Median age was 57 (range 39–76; 16M/9F); 83% had bone marrow involvement, and 32% had other extranodal disease at diagnosis. On ITT analysis, overall response rate (ORR) was 68% after chemoTx (CR 28%/PR 40%). 17 pts received HSCT (13 autologous and 4 allogeneic); 4 eligible pts did not proceed to transplant due to progressive disease. Following HSCT, ORR was 77%. There were no treatment-related deaths. 5 pts experienced reversible non-hematologic grade 4 toxicities (2 bilirubin, 1 stomatitis, 1 infection, and 1 renal failure). On ITT, 5-year EFS and OS for all pts is 35% and 50%, respectively (Figure 1). With a median follow-up of 61 mos, 5-year EFS and OS for pts who received aHSCT is 54% and 75%, respectively (Figure 2). This includes 7/13 aHSCT pts who are alive and disease free at 49, 51, 61, 63, 61, 77, and 80 mos. Patients who received aHSCT had significantly improved survival compared to pts who received allogeneic or no HSCT (p=0.003 EFS and p=0.001 OS by logrank test). We conclude that CTAP/VMAC induction chemoTx followed by aHSCT in first remission for newly diagnosed MCL results in durable EFS and OS. Incorporation of monoclonal antibody and other novel targeted agents should further improve pt outcomes. Figure 1. 5-year survival rates (confidence interval, CI) for all 25 newly diagnosed MCL pts: EFS 35% (CI, 17%–53%), OS 50% (CI, 29%–68%). Figure 1. 5-year survival rates (confidence interval, CI) for all 25 newly diagnosed MCL pts: EFS 35% (CI, 17%–53%), OS 50% (CI, 29%–68%). Figure 2. 5-year survival rates (confidence interval, CI) for 13 pts who received aHSCT in first CR/PR: EFS 54% (CI, 25%–76%), OS 75% (CI, 41%–91%). Figure 2. 5-year survival rates (confidence interval, CI) for 13 pts who received aHSCT in first CR/PR: EFS 54% (CI, 25%–76%), OS 75% (CI, 41%–91%).

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