(F7) Randomized phase II study with GM-CSF and low-dose ARAC in patients with “high risk” myelodysplastic syndromes

1991 ◽  
Vol 15 ◽  
pp. 14
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Myelodysplastic Syndromes ◽  
Low Dose ◽  
Phase Ii Study ◽  
Gm Csf ◽  
Randomized Phase Ii

A phase II study of intensive chemotherapy with fludarabine, cytarabine, and mitoxantrone in P glycoprotein-negative high-risk myelodysplastic syndromes

2004 ◽  
Vol 5 (3) ◽  
pp. 209-215 ◽  
Author(s):  
Thomas Prébet ◽  
Sophie Ducastelle ◽  
Stephan Debotton ◽  
Aspasia Stamatoullas ◽  
Eric Deconinck ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Myelodysplastic Syndromes ◽  
Phase Ii Study ◽  
Intensive Chemotherapy ◽  
P Glycoprotein

Rituximab for Graft-Versus-Host-Disease-Prophylaxis after Allogeneic Stem Cell Transplantation Given as Treatment of High Risk Relapse of Aggressive Lymphoma: Results of a Randomized Phase II Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1974-1974 ◽  
Author(s):  
Bertram Glass ◽  
Justin Hasenkamp ◽  
Anke Görlitz ◽  
Peter Dreger ◽  
Jörg Schubert ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Randomized Phase Ii ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors

Abstract Background: High dose therapy (HDT) followed by autologous stem cell support has poor outcome in patients with primary progressive lymphoma or relapse after primary HDT. Allogeneic SCT may help these patients by exerting an GVL effect. Its use however is hampered by high incidence of severe GVHD and non-relapse mortality in this population. Rituximab has been claimed to reduce the incidene of GVHD without negative impact on the relapse rate. Patients and Methods : We initiated a randomized phase II study using intermediate conditioning (Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg) followed by GVHD prophylaxis with short term mycophenolat mofetil plus tacrolimus. Anti-thymozyte globulin (ATG) was given due to center decision. Patients were randomized to receive two times four doses of rituximab (375 mg/m2) post transplant starting day +21 and day +175 or no additional GVHD prophylaxis. From June 2004 to July 2007 sixty five patients with aggressive NHL were enrolled and 59 were eligible for analysis. Thirty one pts had diffuse large B cell NHL, 3 patients follicular lymphoma grade 3, 7 pts blastic mantle cell lymphoma, 2 pts aggressive marginal zone lymphoma, 2 patients lymphoblastic B cell lymphoma, and 12 T cell lymphoma. 42 (71%) pts received at least one cycle of HDT and autologous SCT prior to alloSCT; 78% had early relapse ( < 12 months) or primary progressive disease, 59% chemo-refractory disease and 48% had progressive disease with high or high intermediate age adjusted IPI immediately prior to conditioning. Results: Allo-PBPC were obtained from HLA-identical siblings in 17 pts, from matched unrelated donors in 32 pts and from one locus mismatched unrelated donors in 10 pts. 33 patients did receive ATG. Median observation time of surviving patients is 1,8 years. 30 pts died, in 19 patients death was attributed to treatment related causes. After one year, estimated overall survival is 49%, progression free survival is 39%, relapse rate is 28 % and incidence of GVHD > grade 1 is 73%. The last documented lymphoma progress occurred at day 288 after alloSCT. There are no significant differences in OS, PFS and GvHD in relationship to the application of Rituximab. Conclusion: Intermediate intensity conditioning followed by allogeneic SCT is a valuable treatment option in patients with high-risk relapse of aggressive NHL. The incidence of GVHD and non-relapse mortality is high. On the background of this very high basic incidence of GVHD, we did not find a significant impact of post transplant rituximab on GVHD, relapse rates or survival, respectively. Therefore, ATG will be added as an obligatory part of the conditioning regimen in the next study phase in additional 30 patients

Long-Term Follow Up Of a Randomized Phase II Study Of The JAK2-Selective Inhibitor Fedratinib (SAR302503) In Patients With Myelofibrosis (MF)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4047-4047 ◽  
Author(s):  
Animesh Pardanani ◽  
Ayalew Tefferi ◽  
Catriona HM Jamieson ◽  
Nashat Y Gabrail ◽  
Claudia Lebedinsky ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Hematologic Toxicity ◽  
Costal Margin ◽  
Spleen Volume ◽  
Randomized Phase Ii ◽  
Grade 3

Abstract Background We previously reported that patients with MF enrolled in a randomized Phase II study of fedratinib (SAR302503) (ARD11936; NCT01420770) had clinically meaningful reductions in splenomegaly and improvements in MF-associated constitutional symptoms after 24 weeks of treatment (Haematologica 2013;98:S1113). Here, we report updated efficacy and safety results from this study after 48 weeks of treatment (end of Cycle 12). Methods Patients with intermediate risk-2 or high-risk MF were randomized to receive once-daily fedratinib at doses of 300 mg, 400 mg, or 500 mg, for consecutive 4-weekly cycles, until disease progression or unacceptable toxicity. Eligible patients were aged ≥18 years, with palpable splenomegaly (5 cm below costal margin), and a platelet count ≥50 × 109/L. The primary measure for this study was percent change in spleen volume from baseline at the end of Cycle 3 (Blood 2012:120;Abstract 2837. Haematologica 2013;98:S1113). Endpoints for the current analysis included spleen response (≥35% reduction in spleen volume from baseline, assessed by a blinded independent central review by MRI), safety, and changes in bone marrow fibrosis (BMF). Results A total of 31 patients were randomized and treated: median age 63 years, 52% male, 58% primary MF, 58% high-risk MF, 90% JAK2V617F positive. The median numbers of treatment cycles were 12, 14, and 13 in the 300 mg, 400 mg and 500 mg dose groups, respectively, with median durations of exposure of 48.2, 56.2, and 52.4 weeks. At the cut-off date for this analysis, 21 patients (68%) remained on treatment; the most common reasons for treatment discontinuation were adverse events (AEs) (n=5) and withdrawal of consent (n=2). Overall, 58% (18/31) of patients achieved a spleen response at any time during treatment. The median spleen response duration was >35 weeks at all doses (Table). At Week 48, a spleen response was achieved by 30% (3/10), 80% (8/10), and 45% (5/11) of patients in the 300 mg, 400 mg, and 500 mg groups, respectively. Responses were generally maintained across all treatment groups. From Week 24 to Week 48 two additional patients achieved a spleen response (both in the 400 mg group), while one patient in the 500 mg group did not maintain a response (this patient had a fedratinib dose reduction to 200 mg). Changes in BMF up to Week 48 are being evaluated. The most common non-hematologic AE was diarrhea, with a Grade 3 rate of 13% (4/31 patients) but no Grade 4 cases were recorded. The rates of diarrhea decreased after the first cycle of treatment; from Cycle 2, the incidence of diarrhea (any grade) did not exceed 16% (5/31) at any cycle, and only one case of diarrhea was reported at Week 48 (end of Cycle 12). Anemia was the most-common hematologic toxicity, with a Grade 3 rate of 58% (18/31); no Grade 4 cases were reported. All Grades thrombocytopenia occurred in 55% (17/31) of patients, Grade 3 in three patients, and Grade 4 in two patients. Discontinuation of treatment due to AEs occurred in five patients over the 48 weeks (300 mg [n=2]; 400 mg [n=2]; 500 mg [n=1]), with two cases reported after Week 24 (dyspnea and leukocytosis [400 mg]; anemia and thrombocytopenia [500 mg]). There were 2 deaths (one in the 300 mg group due to unknown reasons [85 days after fedratinib discontinuation] and one in the 500 mg group due to disease progression [36 days after fedratinib discontinuation]). No cases of leukemic transformation were reported. Conclusions This updated analysis of the ARD11936 Phase II trial shows that treatment with fedratinib results in durable reductions in splenomegaly in patients with MF. No additional safety signals were observed with prolonged exposure to fedratinib. This study was sponsored by Sanofi. Disclosures: Pardanani: Sanofi, Bristol Myers Squibb, PharmaMar and JW Pharma: Clinical trial support Other. Jamieson:J&J, Roche: Research Funding; Sanofi: Membership on an entity’s Board of Directors or advisory committees. Lebedinsky:Sanofi: Employment. Gao:Sanofi: Employment. Talpaz:Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Research Funding; Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Speakers Bureau.

Elotuzumab with lenalidomide and low-dose dexamethasone in patients with relapsed multiple myeloma: A randomized phase II study.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 8014-8014 ◽  
Author(s):  
P. G. G. Richardson ◽  
P. Moreau ◽  
A. J. Jakubowiak ◽  
T. Facon ◽  
S. Jagannath ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Study ◽  
Randomized Phase Ii

Randomized phase II study of 6 versus 12 months of adjuvant imatinib for patients with intermediate- or high-risk GIST.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 9-9
Author(s):  
Kazuya Muguruma ◽  
Yukinori Kurokawa ◽  
Toshimasa Tsujinaka ◽  
Junya Fujita ◽  
Takuya Nakai ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Hazard Ratio ◽  
P Value ◽  
Adjuvant Imatinib ◽  
Randomized Phase Ii ◽  
Ecog Ps

9 Background: The Z9001 study revealed adjuvant imatinib for 1 year significantly improved RFS in GIST patients (pts). The SSGXVIII study compared 3 years with 1 year of adjuvant imatinib for high risk GIST pts, but there was no study to evaluate shorter period of imatinib administration than 1 year. We conducted a randomized phase II study to compare 6 months (6-mo) with 12 months (12-mo) adjuvant imatinib for intermediate or high risk GIST pts. Methods: Inclusion criteria included ECOG-PS of 0 or 1, age between 20 and 79 years, and primary KIT-positive GIST with intermediate or high risk according to the Fletcher criteria. Pts were randomized assigned to the 6-mo or 12-mo treatment of imatinib 400 mg/day after complete resection. The primary endpoint was recurrence-free survival (RFS). The study was designed as a randomized screening trial to evaluate non-inferiority with margin of hazard ratio 1.67, 1-sided alpha 0.2 and power 0.8. Results: Ninety-two pts were randomly allocated the 6-mo group (n=45) or the 12-mo group (n=47) between Dec 2007 and Aug 2011, which was well balanced for baseline characteristics. One patient was ineligible due to non-GIST (desmoid) tumor at a central review. The proportions of pts completed their assigned adjuvant treatment were 80% in the 6-mo and 70% in the 12-mo group. The first interim analysis was conducted at Sep 2012 with the median follow-up time of 33 months. The 1- and 2-year RFS were 82% and 65% in the 6-mo group and 96% and 86% in the 12-mo group, respectively. Hazard ratio of recurrence was 1.81 (95%CI: 0.84-3.91), and the 2-sided log-rank p value was 0.12. Adjuvant imatinib was well tolerated, with one patient of Gr. 4 rash and no treatment-related death. Because of the lower efficacy of the 6-mo group than expected, the Data and Safety Monitoring Committee recommended the early release of first interim analysis results. Conclusions: Adjuvant Imatinib for 6-mo was inferior in efficacy to that for 12-mo in terms of RFS. Shortening of the adjuvant imatinib duration is not recommended for intermediate or high risk GIST pts. Clinical trial information: UMIN000000950.

scholarly journals Addition of Lenalidomide (LEN) to Azacitidine (AZA) (Combined vs Sequential Treatment) in High-Risk Myelodysplastic Syndromes (MDS): A Randomized Phase II Multicenter Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4648-4648 ◽  
Author(s):  
Carlo Finelli ◽  
Cristina Clissa ◽  
Matilde Y Follo ◽  
Marta Stanzani ◽  
Paolo Avanzini ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Phase Ii ◽  
Myelodysplastic Syndromes ◽  
Single Agent ◽  
Sequential Treatment ◽  
Refractory Anemia ◽  
Hematologic Toxicity ◽  
Mutational Status ◽  
Randomized Phase Ii

Abstract Introduction. Azacitidine (AZA) as single agent has been shown to improve overall survival in high-risk myelodysplastic syndromes (MDS), with an overall response rate (ORR) of 50-60% (Silverman 2002; 2006; Fenaux 2009). However as a significant proportion of patients (pts) do not respond to treatment, and moreover, as the the duration of therapeutic response to AZA is limited, several attempts have been made to associate AZA with other drugs, with the aim to improve the outcome. In particular, the addition of lenalidomide (LEN) to AZA, either administered concurrently (Sekeres, 2010; 2012), or sequentially (Platzbecker, 2013), has shown promising results, although these data await confirmation by larger series of pts. The aim of this study was to evaluate the efficacy (ORR) and safety of the combination vs the sequential use of AZA and LEN in high-risk MDS pts. Moreover, as in previous studies we demonstrated that the increase in PI-PLCβ1 gene expression during AZA treatment is related to haematological response and frequently anticipates the response (Follo, 2009; 2012), another aim of our study was to assess the evaluation of PI-PLCβ1 expression as early predictive biomarker of response also with the association of AZA and LEN, and to look for other possible biomarkers able to predict response, as the mutational status assessed by next generation sequency (NGS). Methods. This is a randomized, phase II, multicenter, open label study, including pts with MDS (according to WHO 2008 classification) with International Prognostic Scoring System (IPSS) risk High or Intermediate-2, without previous treatment with AZA or LEN. ARM 1 (combined treatment): AZA: 75 mg/m2/day (days 1-5) I.C. + LEN: 10 mg/day (days 1-21), orally, every 4 weeks. ARM 2 (sequential treatment): AZA: 75 mg/m2/day (days 1-5) I.C. + LEN: 10 mg/day (days 6-21), orally, every 4 weeks. The treatment for both arms was planned for 8 cycles (32 weeks) in the absence of disease progression or unacceptable toxicity. A sample size of 44 pts was planned. Results. From March 2013, 40 pts (23 males), with a median age of 72 (48-83 yrs) were enrolled, from 13 hematologic italian Centers. At baseline, WHO diagnosis was: Refractory Cytopenia with Multilineage Dysplasia (RCMD): 3 pts; Refractory Anemia with Excess of Blasts-1 (RAEB-1): 9 pts; RAEB-2: 23 pts; MDS-unclassified (MDS-U): 5 pts; IPSS risk was: Intermediate-2: 29 pts; High: 6 pts; not determined (N.D.) (because of lack of cytogenetic data): 5 pts. (all with RAEB-2). IPSS cytogenetic risk was: intermediate in 10 pts and high in 9 pts (3 with complex karyotypes and 6 with isolated -7 or 7q-). 5 pts showed del5q (in 3 cases in the context of a complex karyotype, and in 1 case associated with another single additional cytogenetic alteration). 2 pts had therapy-related MDS. 21 pts (52.5%) were transfusion-dependent at baseline. 19 pts were randomly assigned to ARM 1, and 21 pts to ARM 2. At the time of this analysis, 22/40 pts (55%) completed ≥ 6 cycles of treatment, and are evaluable for response. 13/22 pts (59,1%) showed a favourable response to treatment, following the International Working Group (IWG) criteria (Cheson, 2006): 2 pts achieved Complete Remission (CR), 2 pts attained Partial Remission (PR), 2 pts showed Marrow Complete Remission (mCR), and 7 pts obtained Hematological Improvement (HI), while the 9 non responder pts maintained a Stable Disease (SD). Responder pts were 7/10 (70%) in ARM 1 (2 CR; 1 PR; 4 HI), and 6/12 (50%) in ARM 2 (1 CR; 1 PR; 2 mCR; 2 HI), respectively. Median time to first response: 2 (2-7) months. A significant toxicity (grade > 2) was observed in 10/40 (25%) pts. 15/40 pts (37,5%) had a dose reduction of LEN because of hematologic or non-hematologic toxicity. 8 pts (20%) early discontinued therapy before completing the planned 8 cycles, because of prolonged thrombocytopenia (1 pt), death (3 pts), evolution into acute myeloid leukemia (AML) (2 pts) and withdrawal of consent (2 pts), respectively. Causes of death were: febrile neutropenia, myocardial infarction and sudden death, respectively . Conclusions. Our results, although preliminary, seem to confirm the feasibility of the association of AZA and LEN in high-risk MDS pts. More data are needed in order to compare the efficacy and safety of combined vs sequential treatment and vs AZA monotherapy. Moreover, possible relationships with signal transduction pathways and with mutational status are under evaluation. Disclosures Finelli: Celgene: Research Funding, Speaker Other; Novartis: Speaker, Speaker Other; Janssen: Speaker, Speaker Other. Off Label Use: Lenalidomide in higher-risk MDS and AML. Cavo:Celgene: Consultancy, Honoraria, Speakers Bureau.

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