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AzTrials

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromePhase 2NCT00795002

Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

A Phase 2 study testing alvocidib, mitoxantrone hydrochloride and cytarabine in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 2 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 randomized phase II trial is studying two different schedules of alvocidib to compare how well they work when given together with cytarabine and mitoxantrone in treating patients with newly diagnosed acute myeloid leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alvocidib, mitoxantrone hydrochloride and cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
2 sitesUnited States
Study dates
Nov 2008to Sep 2012
Phase
Phase 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologically confirmed newly diagnosed acute myeloid leukemia (AML) meeting the following criteria:
  • Subtypes M0, M1, M2, M4-7
  • No acute promyelocytic leukemia (M3)
  • At least 50 years of age OR >= 18 years of age with >= 1 of the following poor-risk disease features:
  • Antecedent hematologic disorder, including myelodysplastic syndromes (MDS)-related AML or prior myeloproliferative disorder (MPD)
  • Treatment-related AML, AML with trilineage dysplasia
Show all 28Show fewer
  • Myeloid sarcoma, myeloid proliferations related to Down Syndrome, or blastic plasmacytoid dendritic cell neoplasm
  • AML with trilineage dysplasia
  • AML with adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q, or 17p; t[6;9]; t[9;22]; trisomy 8; trisomy 13, complex karyotypes [>= 3 unrelated abnormalities]),
  • No hyperleukocytosis with >= 50,000 blasts/uL (leukapheresis or hydroxyurea allowed for cytoreduction immediately prior to the first dose of alvocidib)
  • No active CNS leukemia
  • ECOG performance status 0-2
  • Serum creatinine =< 2.0 mg/dL
  • ALT/AST =< 5 times upper limit of normal
  • Bilirubin =< 2.0 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • No active uncontrolled infection
  • Infection that is under active treatment allowed provided it is controlled with antibiotics
  • No other life-threatening illness
  • No mental deficits and/or psychiatric history that would preclude giving informed consent or following study requirements
  • At least 24 hours since prior leukapheresis or hydroxyurea for cytoreduction
  • Prior non-cytotoxic therapies (e.g., thalidomide or lenalidomide, interferon, cytokines, low-dose 5-azacytidine, or low-dose cytoxan) for MDS or MPD allowed
  • Prior chemotherapy or bone marrow/stem cell transplantation for non-AML malignancy allowed
  • No prior alvocidib
  • No other concurrent chemotherapy, radiotherapy, or immunotherapy
  • No other concurrent investigational or commercially-available antitumor therapies for AML
  • LVEF >= 45%

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Randomized Phase II Study Comparing Two Administration Schedules of Flavopiridol (Alvocidib, NSC 649890, IND 46, 211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone Hydrochloride for Adults With Newly Diagnosed, Previously Untreated, Poor Risk Acute Myelogenous Leukemias (AML)

This randomized phase II trial is studying two different schedules of alvocidib to compare how well they work when given together with cytarabine and mitoxantrone in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as alvocidib, cytarabine, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known which schedule of alvocidib is more effective when given together with cytarabine and mitoxantrone in treating patients with acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the efficacy of two different schedules (bolus vs "hybrid bolus-infusion") of alvocidib followed by cytarabine and mitoxantrone hydrochloride in patients with newly diagnosed acute myeloid leukemia (AML) with poor-risk features.

SECONDARY OBJECTIVES:

  1. To compare the toxicities of these regimens. II. To determine the disease-free survival and overall survival of patients who demonstrate a response to these regimens.

III. To compare the pharmacokinetics of alvocidib when administered in two different schedules (bolus vs "hybrid bolus-infusion").

IV. To describe alvocidib-induced alterations in AML blast cell expression of selected target mRNA and proteins.

  1. To describe alvocidib-induced alterations in AML blast cell growth kinetic parameters.

OUTLINE: This is a multicenter study. Patients are stratified according to antecedent hematologic disorder of >= 6 months duration prior to transformation to acute myeloid leukemia (AML) and any prior antecedent therapy for myelodysplastic syndromes or myeloproliferative disorder. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.

ARM II: Patients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.

Patients achieving partial or complete response (CR) after the first course of treatment may receive a second course of treatment 35-63 days following blood count recovery and/or undergo allogeneic bone marrow transplantation. Patients >= 50 years of age with t (8;21), inv (16), or t(16;16) AML who achieve CR after the first course of treatment may receive 3-4 courses of high-dose cytarabine consolidation therapy.

Bone marrow and/or blood samples are collected at baseline and periodically during study for correlative laboratory studies, including pharmacokinetic studies by liquid chromatography and tandem mass spectrometry, analysis of blast cell growth kinetic parameters by flow cytometry, and blast cell expression of selected target mRNA and protein by quantitative RT-PCR and western blotting.

After completion of study therapy, patients are followed periodically.

Being tested
alvocidib, mitoxantrone hydrochloride, cytarabine, pharmacological study, laboratory biomarker analysis
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, 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.

  • alvocidibDrug

    Also called FLAVO, flavopiridol, HMR 1275, L-868275

    Given IV

  • mitoxantrone hydrochlorideDrug

    Also called CL 232315, DHAD, DHAQ, Novantrone

    Given IV

  • cytarabineDrug

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

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00795002
Study groupRoleWhat they receive
Arm IExperimentalPatients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV continuously over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 60-120 minutes on day 9.
Receives: Drug: alvocidib; Drug: mitoxantrone hydrochloride; Drug: cytarabine; Other: pharmacological study; Other: laboratory biomarker analysis
Arm IIExperimentalPatients receive alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 1-3. Patients also receive cytarabine and mitoxantrone hydrochloride as in arm I.
Receives: Drug: alvocidib; Drug: mitoxantrone hydrochloride; Drug: cytarabine; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. Complete Response

    Bone marrow showing less than 5% leukemic blasts with normal maturation of all cell lines, an ANC of at least 1000/uL and a platelet count of 100,000/uL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. Repeat marrow confirmation 4-6 weeks following the marrow documenting CR is not required due to the need for continued treatment in CR.

    Measured: 1 year

Secondary outcomes (2)

  1. Number of Participants Experiencing Death From Any Cause Within 60 Days of Starting FLAM

    Toxicity defined as death from any cause within 60 days of starting FLAM.

    Measured: 60 days

  2. Disease-free Survival

    This will be defined as the time between study entry and the first date that recurrent or progressive disease is objectively documented, or death from any cause occurs.

    Measured: up to 2 years

Timeline

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

  1. First posted21 Nov 2008 (estimated)
  2. Study startNov 2008
  3. Primary completionNov 2010
  4. Study completionSep 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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00795002
Sponsor's protocol ID
NCI-2009-00298
Other IDs
NCI-2009-00298, CDR0000625222, J0856, 8237, P30CA006973, U01CA070095
Status last verified
Aug 2018
First submitted
20 Nov 2008
Last updated
7 Aug 2018

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing alvocidib, mitoxantrone hydrochloride and cytarabine in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 2 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 28 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 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 phase mean?

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 Dec 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?

Complete Response (time frame: 1 year). 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 NCT00795002.

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 7 Aug 2018.

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