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Acute Myeloid LeukemiaPhase 1/2NCT00742625

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

A Phase 1/2 study testing daunorubicin hydrochloride, cytarabine and bortezomib in people with Acute Myeloid Leukemia and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 60 to 75 years
What is being tested?
daunorubicin hydrochloride, cytarabine and bortezomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
22 sitesUnited States
Study dates
Sep 2008to Dec 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 20Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • University of Chicago

    Chicago, Illinois, 60637

  • University of Missouri - Ellis Fischel

    Columbia, Missouri, 65212

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Kinston Medical Specialists PA

    Kinston, North Carolina, 28501

  • North Shore University Hospital

    Manhasset, New York, 11030

  • North Shore-LIJ Health System CCOP

    Manhasset, New York, 11030

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • North Shore-LIJ Health System/Center for Advanced Medicine

    New Hyde Park, New York, 11040

  • Mount Sinai Medical Center

    New York, New York, 10029

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Florida Hospital

    Orlando, Florida, 32803

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • Lombardi Comprehensive Cancer Center at Georgetown University

    Washington D.C., District of Columbia, 20057

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
daunorubicin hydrochloride, cytarabine, bortezomib
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • daunorubicin hydrochlorideDrug

    Also called Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin

    Given IV

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given IV

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

Study groups in NCT00742625
Study groupRoleWhat they receive
Treatment (daunorubicin hydrochloride and bortezomib)ExperimentalSee Detailed Description
Receives: Drug: daunorubicin hydrochloride; Drug: cytarabine; Drug: bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 months

  2. Participants Experiencing a Dose-limiting Toxicity (DLT) of Bortezomib When Administered in Combination With Intermediate-dose Cytarabine

    DLTs were considered only during the first cycle of consolidation therapy and included grade 3 or 4 sensory or autonomic neuropathy, persistent grade 4 thrombocytopenia or neutropenia at day 42 in the absence of AML,any grade 4 or 5 nonhematologic toxicity, and any grade 3 nonhematologic toxicity (excluding neuropathy and toxicities secondary to neutropenia and sepsis) that did not resolve to grade 2 by day 42 unless attributable to persistent or recurrent AML. Grade 4 anorexia (requiring total parenteral nutrition) and grade 4 fatigue (requiring bed rest) were not considered DLTs.

    Toxicity was graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grading scale is as follows: grade 1: mild; grade 2: moderate; grade 3: Severe; grade 4: Life Threatening; grade 5: Death.

    Measured: during consolidation cycle 1 (42 days)

Secondary outcomes (2)

  1. Disease-free Survival

    Disease-free survival (DFS) was measured as the interval from achievement of CR until relapse or death, regardless of cause. DFS was estimated using the Kaplan Meier method.

    Measured: Duration of study (up to 10 years)

  2. Overall Survival

    Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.

    Measured: Duration of study (up to 10 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionJul 2010
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00742625
Sponsor's protocol ID
NCI-2009-00443
Other IDs
NCI-2009-00443, CDR0000612758, CALGB 10502, CALGB-10502, U10CA031946, P30CA014236
Status last verified
Jun 2014
First submitted
27 Aug 2008
Last updated
12 Sep 2014

Publications

  • Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.

    PubMed 36184192

  • Walker CJ, Kohlschmidt J, Eisfeld AK, Mrozek K, Liyanarachchi S, Song C, Nicolet D, Blachly JS, Bill M, Papaioannou D, Oakes CC, Giacopelli B, Genutis LK, Maharry SE, Orwick S, Archer KJ, Powell BL, Kolitz JE, Uy GL, Wang ES, Carroll AJ, Stone RM, Byrd JC, de la Chapelle A, Bloomfield CD. Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia. Clin Cancer Res. 2019 Nov 1;25(21):6524-6531. doi: 10.1158/1078-0432.CCR-19-0725. Epub 2019 Aug 2.

    PubMed 31375516

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing daunorubicin hydrochloride, cytarabine and bortezomib in people with Acute Myeloid Leukemia and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Remission Induction Response (time frame: 2 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00742625, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2014.

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