Dose Escalation and Phase II Study of Bortezomib (IND #58443, NSC # 681239) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years
I. To define the remission induction response rate (complete response [CR] and CR with
incomplete platelet recovery [CRp]) in older patients with previously untreated acute
myeloid leukemia treated with induction therapy comprising bortezomib in combination with
daunorubicin hydrochloride and cytarabine.
II. To define the maximum tolerated dose of bortezomib when administered in combination with
intermediate-dose cytarabine after induction therapy.
I. To describe the disease-free survival of patients treated with this regimen.
II. To describe the overall survival of patients treated with this regimen.
III. To evaluate the treatment-related toxicities in these patients.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Doses of bortezomib are
escalated during remission consolidation therapy.
- Remission induction therapy:
- Remission induction course 1: Patients receive bortezomib IV over 3-5 seconds on
days 1, 4, 8, and 11; daunorubicin hydrochloride IV on days 1-3; and cytarabine IV
continuously over 168 hours on days 1-7.
After completion of remission induction course 1, patients undergo bone marrow aspiration
and biopsy for evaluation of response. Patients achieving a complete response (CR) or
partial response (PR) proceed to remission consolidation therapy. Patients achieving a CR
with incomplete platelet recovery (CRp) proceed to remission consolidation therapy after
platelet counts recover. Patients with persistent leukemia (≥ 20% bone marrow cellularity
and ≥ 5% bone marrow myeloblasts) proceed to remission induction course 2.
- Remission induction course 2: Patients receive bortezomib IV over 3-5 seconds on days 1
and 4; daunorubicin hydrochloride IV on days 1 and 2; and cytarabine IV continuously
over 120 hours on days 1-5.
After completion of remission induction course 2, patients undergo bone marrow aspiration
and biopsy for evaluation of response. Patients achieving a CR or PR proceed to remission
consolidation therapy. Patients achieving a CRp proceed to remission consolidation therapy
after platelet counts recover. Patients with residual leukemia who do not meet the criteria
for PR are removed from the study.
- Remission consolidation therapy: Patients receive bortezomib IV over 3-5 seconds on
days 1, 4, 8, and 11 and intermediate-dose cytarabine IV over 3 hours on days 1-5.
Patients then undergo bone marrow aspiration and biopsy for evaluation of response.
Patients achieving a CR or who demonstrate continuing CR receive a second course of
remission consolidation therapy beginning 2-4 weeks after blood counts recover.
After completion of study therapy, patients are followed every 2 months for 2 years, every 3
months for 2 years, and then annually for up to 10 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Remission Induction Response
Response was calculated according to Revised International Working Group (IWG) criteria for Acute myeloid leukemia (AML) A response was defined as the portion of participants who achieved a complete response (CR) or CR with incomplete platelet recovery(CRp) during induction. A CR is defined as those with > 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, <5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils > 1000 mL and platelets >= 100,000 mL). A CRp is defined as a CR except platelets < 100,000 mL without need for transfusion.
Eyal C. Attar, MD
Massachusetts General Hospital
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - North Shore University Hospital||Manhasset, New York 11030|
|Holden Comprehensive Cancer Center at University of Iowa||Iowa City, Iowa 52242-1002|
|Ellis Fischel Cancer Center at University of Missouri - Columbia||Columbia, Missouri 65203|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Washington Cancer Institute at Washington Hospital Center||Washington, District of Columbia 20010|
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|Florida Hospital Cancer Institute at Florida Hospital Orlando||Orlando, Florida 32803-1273|
|Mount Sinai Medical Center||New York, New York 10029|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Wayne Memorial Hospital, Incorporated||Goldsboro, North Carolina 27534|
|Greenebaum Cancer Center at University of Maryland Medical Center||Baltimore, Maryland 21201|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center||Omaha, Nebraska 68198-7680|
|Lombardi Comprehensive Cancer Center at Georgetown University Medical Center||Washington, District of Columbia 20007|
|CancerCare of Maine at Eastern Maine Medical Center||Bangor, Maine 04401|
|Don Monti Comprehensive Cancer Center at North Shore University Hospital||Manhasset, New York 11030|
|Virginia Commonwealth University Massey Cancer Center||Richmond, Virginia 23298-0037|
|Fort Wayne Medical Oncology and Hematology||Fort Wayne, Indiana 46815|
|Cancer Institute of New Jersey at Cooper - Voorhees||Voorhees, New Jersey 08043|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|
|Tunnell Cancer Center at Beebe Medical Center||Lewes, Delaware 19958|
|Union Hospital Cancer Program at Union Hospital||Elkton MD, Maryland 21921|
|Monter Cancer Center of the North Shore-LIJ Health System||Lake Success, New York 11042|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center||Columbus, Ohio 43210-1240|
|Dana-Farber/Brigham and Women's Cancer Center||Boston, Massachusetts 02115|
|Kinston Medical Specialists||Kinston, North Carolina 28501|