scholarly journals A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 117 (6) ◽  
pp. 1828-1833 ◽  
Author(s):  
Todd A. Fehniger ◽  
Geoffrey L. Uy ◽  
Kathryn Trinkaus ◽  
Alissa D. Nelson ◽  
Jeffery Demland ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Initial Therapy ◽  
Clinical Activity ◽  
High Dose ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Acute Myeloid

Abstract Older patients with acute myeloid leukemia (AML) have limited treatment options and a poor prognosis, thereby warranting novel therapeutic strategies. We evaluated the efficacy of lenalidomide as front-line therapy for older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received high-dose (HD) lenalidomide at 50 mg daily for up to 2 28-day cycles. If patients achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) or did not progress after 2 cycles of HD lenalidomide, they received low-dose lenalidomide (10 mg daily) until disease progression, an unacceptable adverse event, or completion of 12 cycles. Thirty-three AML patients (median age, 71 years) were enrolled with intermediate (55%), unfavorable (39%), or unknown (6%) cytogenetic risk. Overall CR/CRi rate was 30%, and 53% in patients completing HD lenalidomide. The CR/CRi rate was significantly higher in patients presenting with a low (< 1000/μL) circulating blast count (50%, P = .01). The median time to CR/CRi was 30 days, and duration of CR/CRi was 10 months (range, 1- ≥ 17 months). The most common grades ≥ 3 toxicities were thrombocytopenia, anemia, infection, and neutropenia. HD lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of lenalidomide in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as #NCT00546897.

scholarly journals Current Therapeutic Results and Treatment Options for Older Patients with Relapsed Acute Myeloid Leukemia

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 224 ◽  
Author(s):  
Felicetto Ferrara ◽  
Federica Lessi ◽  
Orsola Vitagliano ◽  
Erika Birkenghi ◽  
Giuseppe Rossi
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Randomized Clinical Trials ◽  
Clinical Decision Making ◽  
New Drugs ◽  
Clinical Activity ◽  
High Dose ◽  
Therapeutic Results ◽  
Acute Myeloid

Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months. A general agreement exists concerning the administration of aggressive salvage therapy in young adults followed by allogeneic stem cell transplantation; on the contrary, different therapeutic approaches varying in intensity, from conventional salvage chemotherapy based on intermediate–high-dose cytarabine to best supportive care, are currently considered in the relapsed, older AML patient population. Either patients’ characteristics or physicians’ attitudes count toward the process of clinical decision making. In addition, several new drugs with clinical activity described as “promising” in uncontrolled single-arm studies failed to improve long-term outcomes when tested in larger randomized clinical trials. Recently, new agents have been approved and are expected to consistently improve the clinical outcome for selected genomic subgroups, and research is in progress in other molecular settings. While relapsed AML remains a tremendous challenge to both patients and clinicians, knowledge of the molecular pathogenesis of the disease is fast in progress, potentially leading to personalized therapy in most patients.

scholarly journals Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study

2019 ◽  
Vol 3 (4) ◽  
pp. 508-518 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Yasmin Abaza ◽  
Koichi Takahashi ◽  
Bruno C. Medeiros ◽  
Martha Arellano ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Intensive Therapy ◽  
Single Agent ◽  
Response To Treatment ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Study ◽  
Acute Myeloid

Abstract Pracinostat, a potent oral pan-histone deacetylase inhibitor with modest single-agent activity in acute myeloid leukemia (AML), has shown synergistic antitumor activity when combined with azacitidine. This single-group, multicenter phase 2 study assessed the safety and efficacy of pracinostat combined with azacitidine in patients who were at least 65 years old with newly diagnosed AML and who were ineligible for standard induction chemotherapy. Patients received pracinostat 60 mg/d, 3 d/wk, for 3 consecutive weeks, plus azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle. Primary endpoints were complete remission (CR), CR with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS) rates of the combination. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS) of the regimen. Fifty patients (33 de novo, 12 secondary, and 5 therapy-related AML) were enrolled. Twenty-six patients (52%) achieved the primary endpoint of CR (42%), CRi (4%), and MLFS (6%). Median OS and PFS were 19.1 months (95% confidence interval [CI], 10-26.5 months) and 12.6 months (95% CI, 10-17.7 months), respectively, with a 1-year OS rate of 62%. Forty-three patients (86%) experienced at least 1 grade 3 or worse treatment-emergent adverse event with the combination, with infections (52%), thrombocytopenia (46%), and febrile neutropenia (44%) reported as the most common toxicities. The 30- and 60-day all-cause mortality rates were 2% and 10%, respectively. DNA sequencing revealed somatic mutations at baseline, and clearance rates correlated with response to treatment. Pracinostat plus azacitidine is a well-tolerated and active regimen in the frontline treatment of older patients with AML unfit for intensive therapy. A larger controlled trial is ongoing. This trial was registered at www.clinicaltrials.gov as #NCT01912274.

A Phase 2 Study of Actinium-225 (225Ac)-lintuzumab in Older Patients with Untreated Acute Myeloid Leukemia (AML)

2019 ◽  
Vol 50 (4) ◽  
pp. S109
Author(s):  
Ehab Atallah ◽  
Mark Berger ◽  
Joseph Jurcic ◽  
Gail Roboz ◽  
William Tse ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Acute Myeloid

scholarly journals A Phase 2 Study of Actinium-225 (225Ac)-lintuzumab in Older Patients with Untreated Acute Myeloid Leukemia (AML)

2019 ◽  
Vol 50 (1) ◽  
pp. S37 ◽  
Author(s):  
Ehab Atallah ◽  
Mark Berger ◽  
Joseph Jurcic ◽  
Gail Roboz ◽  
William Tse ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Acute Myeloid

scholarly journals Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation

Blood ◽  
2013 ◽  
Vol 121 (23) ◽  
pp. 4655-4662 ◽  
Author(s):  
Farhad Ravandi ◽  
Mona Lisa Alattar ◽  
Michael R. Grunwald ◽  
Michelle A. Rudek ◽  
Trivikram Rajkhowa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Phase 2 ◽  
Internal Tandem Duplication ◽  
Phase 2 Study ◽  
Key Points ◽  
Acute Myeloid

Key Points Azacytidine and sorafenib are effective in patients with relapsed and refractory FLT3-mutated AML.

scholarly journals A phase 1 study of azacitidine with high-dose cytarabine and mitoxantrone in high-risk acute myeloid leukemia

2020 ◽  
Vol 4 (4) ◽  
pp. 599-606 ◽  
Author(s):  
Kirk E. Cahill ◽  
Yasmin H. Karimi ◽  
Theodore G. Karrison ◽  
Nitin Jain ◽  
Margaret Green ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Phase 1 ◽  
High Dose ◽  
Phase 2 ◽  
Phase 1 Study ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract In this phase 1 study, azacitidine (AZA) was given before high-dose cytarabine (HiDAC) and mitoxantrone (mito) based on the hypothesis that epigenetic priming with a hypomethylating agent before cytotoxic chemotherapy would improve response rates in patients with high-risk acute myeloid leukemia (AML), including relapsed/refractory disease. The primary objective was to establish the recommended phase 2 dose of AZA given before standard HiDAC/mito. In a dose escalation scheme, 46 patients (median age, 66 years) received AZA at 37.5, 50, or 75 mg/m2 subcutaneously or IV once daily on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10 (the HiDAC/mito dose was reduced 33% in elderly subjects). Two dose-limiting toxicities occurred (both in the same patient): acute liver failure and kidney injury at the 50 mg/m2 dose. The 30-day induction death rate was 2.2% (1 of 46). The overall response rate, including complete remission and complete remission with incomplete count recovery, was 61% (28 of 46). Previously untreated patients aged ≥60 years with therapy-related AML and de novo AML were more likely to respond than untreated patients with AML progressing from an antecedent hematologic disorder (myelodysplastic syndrome and chronic myelomonocytic leukemia). Patients with favorable European Leukemia Network risk (P = .008), NPM1 mutations (P = .007), or IDH2 mutations (P = .03) were more likely to respond, and those with TP53 mutations (P = .03) were less likely to respond. The recommended phase 2 dose of AZA is 75 mg/m2 per day on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10. This trial was registered at www.clinicaltrials.gov as #NCT01839240.

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