Phase II trial of clofarabine and daunorubicin as induction therapy for acute myeloid leukemia patients greater than or equal to 60 years of age

Vigil, Carlos Enrique; Tan, Wenfeng; Deeb, G. Michael; Sait, Sheila N.J.; Block, AnneMarie W.; Starostik, Petr; Griffiths, Elizabeth A.; Thompson, James E.; Greene, Jessica Davila; Ford, Laurie; Wang, Eunice S.; Wetzler, Meir

doi:10.1016/j.leukres.2013.07.036

Cited by 7 publications

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clofarabine was approved in 2004 for the treatment of relapsed or refractory ALL, and has been further studied as an effective regimen in both MDS and AML (20-23). In 2006, we developed a phase 1-2 protocol incorporating clofarabine at escalating doses into a cytoreductive regimen for hematologic malignancies in order to avoid the use of TBI.…”

Section: Discussionmentioning

confidence: 99%

Second Allogeneic Stem Cell Transplantation for Acute Leukemia Using a Chemotherapy-Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa

Spitzer

Perales

Kernan

et al. 2016

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains one of the leading causes of mortality in patients with leukemia. Treatment options in this population remain limited, with concern for both increased toxicity and further relapse. We treated 18 patients with acute leukemia for marrow +/- extramedullary relapse after a prior alloHSCT, with a myeloablative cytoreductive regimen including clofarabine, melphalan, and thiotepa, followed by a second or third transplant (HSCT2/3) from the same or different donor. All patients were in remission at the time of HSCT2/3. All evaluable patients engrafted. The most common toxicity was reversible transaminitis associated with clofarabine. Two patients died from transplant-related causes. Seven patients relapsed post-HSCT2/3 and died of disease. Nine of 18 patients are alive and disease-free, with a three-year 49% probability of overall survival. Patients whose remission duration after initial alloHSCT was >6 months achieved superior outcomes (3-year OS 74%, 95% CI: 53-100%), compared with those relapsing within 6 months (0%), (p<0.001). This new cytoreductive regimen has yielded promising results with acceptable toxicity for second transplants in patients with high-risk ALL and AML who relapsed after a prior transplant, using various graft and donor options,. This approach merits further evaluation in collaborative group studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Second Allogeneic Stem Cell Transplantation for Acute Leukemia Using a Chemotherapy-Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa

Spitzer

Perales

Kernan

et al. 2016

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation

et al. 2020

View full text Add to dashboard Cite

Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18‐ to 65‐year‐old AML patients refractory to first‐line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high‐dose cytarabine consolidation, with clofarabine (30 mg/m2/d, Days 1‐5), cytarabine (750 mg/m2/d, Days 1‐5), and mitoxantrone (12 mg/m2/d, Days 3‐5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo‐HSCT). The mutational profile of a 69‐gene panel was evaluated. Twenty‐six men and 26 women at a median age of 46 (22‐65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty‐two CR/CRi patients underwent allo‐HSCT. The 2‐year overall survival (OS), relapse‐free survival (RFS), and event‐free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo‐HSCT (P = .005), and superior RFS and EFS were associated with allo‐HSCT (P < .001). Remarkably, CR after CLAM and allo‐HSCT resulted in 2‐year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment‐related mortality and the performance of allo‐HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).

show abstract

The role of Clofarabine in the treatment of adults with acute myeloid leukemia

Fozza

2015

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

Phase II trial of clofarabine and daunorubicin as induction therapy for acute myeloid leukemia patients greater than or equal to 60 years of age

Cited by 7 publications

References 14 publications

Second Allogeneic Stem Cell Transplantation for Acute Leukemia Using a Chemotherapy-Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa

Second Allogeneic Stem Cell Transplantation for Acute Leukemia Using a Chemotherapy-Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa

Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation

The role of Clofarabine in the treatment of adults with acute myeloid leukemia

Contact Info

Product

Resources

About