Phase II trial of hyper CVAD and dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia.
Dasatinib is a second generation tyrosine kinase inhibitor, with activity in imatinib resistant Ph-positive ALL.We have treated 34 patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia(ALL) (n519) or lymphoid blast phase of chronic myelogenous leukemia (CML-LB) (n515) with the combination of dasatinib and the hyper CVAD regimen. Prior regimens included hyper CVAD plus imatinib(n511, 4 had transplant in first CR), other combination chemotherapy (n512), monotherapy with kinase inhibitors other than dasatinib (n59), and investigational agents (n52). Pretreatment ABL mutations were noted in 10 patients. The overall response rate was 91%, with 24 patients (71%) achieving complete response(CR), and 7(21%) CR with incomplete platelet recovery (CRp). Two patients died during induction and one had progressive disease. Twenty-six patients (84%) achieved complete cytogenetic remission after one cycle of therapy. Overall, 13 patients (42%) achieved complete molecular response, and 11 patients (35%) had major molecular response (BCR-ABL/ABL<0.1%). Nine patients proceeded to allogeneic transplantation.Grades 3 and 4 toxicities included hemorrhage, pleural and pericardial effusions and infections. The median follow-up for patients with CML-LB is 37.5 months (range, 7–70 months) with a 3-year overall survival of 70%;68% remained in CR at 3 years. For ALL patients, the median follow-up is 52 months (range, 45–59 months)with a 3-year survival of 26%; 30% remain in CR at 3 years. The combination of Hyper CVAD regimen with dasatinib is effective in patients with relapsed Ph-positive ALL and CML-LB.
Ohad
O
Benjamini
Theresa Liu
TL
Dumlao
Hagop
H
Kantarjian
Susan
S
O'Brien
Guillermo
G
Garcia-Manero
Stefan
S
Faderl
Jeffrey
J
Jorgensen
Rajyalakshmi
R
Luthra
Rebecca
R
Garris
Deborah
D
Thomas
Partow
P
Kebriaei
Richard
R
Champlin
Elias
E
Jabbour
Jan
J
Burger
Jorge
J
Cortes
Farhad
F
Ravandi
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D000069439:Dasatinib; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
D011743:Pyrimidines; D013844:Thiazoles; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069439:Dasatinib