Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

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Brief Title

Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Official Title

Dose Escalation and Phase II Study of Bortezomib (IND #58443) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years

Brief Summary

      This phase II trial studies the side effects and best dose of bortezomib when given together
      with daunorubicin and cytarabine and to see how well it works in treating older patients with
      previously untreated acute myeloid leukemia. Bortezomib may stop the growth of cancer cells
      by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as
      daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells,
      either by killing the cells or by stopping them from dividing. Giving bortezomib together
      with combination chemotherapy may kill more cancer cells.
    

Detailed Description

      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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Remission Induction Response

Secondary Outcome

 Disease-free Survival

Condition

Acute Myeloid Leukemia

Intervention

daunorubicin hydrochloride

Study Arms / Comparison Groups

 Treatment (daunorubicin hydrochloride and bortezomib)
Description:  See Detailed Description

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

95

Start Date

September 2008

Completion Date

December 2012

Primary Completion Date

July 2010

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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)

          -  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:

               -  I) steroids administered for adrenal failure, hypersensitivity reactions, or
                  septic shock;

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

          -  No concurrent palliative radiotherapy
      

Gender

All

Ages

60 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Eyal Attar, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00742625

Organization ID

NCI-2009-00443

Secondary IDs

NCI-2009-00443

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Eyal Attar, Principal Investigator, Cancer and Leukemia Group B


Verification Date

June 2014