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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


Phase 2
60 Years
75 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

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


PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Unequivocally histologically confirmed acute myeloid leukemia (AML)

- At least 20% blasts in the bone marrow based on WHO criteria

- No acute promyelocytic leukemia (M3)

- Antecedent hematologic disorder or myelodysplastic syndromes allowed provided the
patient did not receive cytotoxic chemotherapy, including azacitidine and decitabine,
for their pre-leukemic disorder

- Concurrent enrollment on CALGB-8461 required

PATIENT CHARACTERISTICS:

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No ataxia, cranial neuropathy, or peripheral neuropathy ≥ grade 2

- LVEF ≥ 40% by ECHO or MUGA scan

- No signs or symptoms of congestive heart failure

- DLCO ≥ 50% (corrected for hemoglobin)

PRIOR CONCURRENT THERAPY:

- No prior therapy for leukemia or pre-leukemic disorders, except for the following:

- Emergency leukapheresis

- Emergency treatment for hyperleukocytosis with hydroxyurea

- Cranial radiotherapy for CNS leukostasis (one dose only)

- Growth factor/cytokine support

- No other concurrent chemotherapy, except for the following:

- Steroids administered for adrenal failure, hypersensitivity reactions, or septic
shock

- Hormones administered for non-disease-related conditions (e.g., insulin for
diabetes or estrogens or progestins for gynecologic indications)

- No concurrent palliative radiotherapy

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Remission Induction Response

Outcome Description:

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.

Outcome Time Frame:

2 months

Safety Issue:

No

Principal Investigator

Eyal C. Attar, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Massachusetts General Hospital

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00443

NCT ID:

NCT00742625

Start Date:

September 2008

Completion Date:

December 2012

Related Keywords:

  • Leukemia
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • untreated adult acute myeloid leukemia
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • adult acute megakaryoblastic leukemia (M7)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
University of Chicago Cancer Research CenterChicago, Illinois  60637
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - North Shore University HospitalManhasset, New York  11030
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Washington Cancer Institute at Washington Hospital CenterWashington, District of Columbia  20010
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Mount Sinai Medical CenterNew York, New York  10029
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
CancerCare of Maine at Eastern Maine Medical CenterBangor, Maine  04401
Don Monti Comprehensive Cancer Center at North Shore University HospitalManhasset, New York  11030
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Fort Wayne Medical Oncology and HematologyFort Wayne, Indiana  46815
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Union Hospital Cancer Program at Union HospitalElkton MD, Maryland  21921
Monter Cancer Center of the North Shore-LIJ Health SystemLake Success, New York  11042
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Dana-Farber/Brigham and Women's Cancer CenterBoston, Massachusetts  02115
Kinston Medical SpecialistsKinston, North Carolina  28501