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Acute Myeloid LeukemiaPhase 1NCT03298984

Ph I Study of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML).

A Phase 1 study testing Alvocidib, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by Sumitomo Pharma America, Inc. at 3 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

The purpose of this Phase I study is to determine the safety and tolerability including the maximum dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Alvocidib, Cytarabine and Daunorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
3 sitesUnited States
Study dates
25 Sep 2017to 20 Mar 2020
Phase
Phase 1
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To be eligible for participation in the study, patients must meet all of the following inclusion criteria:
  • Be between the ages of ≥18 and ≤65 years
  • Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria with ≥20% bone marrow blasts based on histology or flow cytometry
  • Be newly diagnosed and previously untreated
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
  • Have a serum creatinine level ≤1.8 mg/dL
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  • Have an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN)
  • Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)
  • Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
  • Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry, for the duration of study participation, and for at least 6 months after the last dose of study drug.
  • Be able to comply with the requirements of the entire study.
  • Provide written informed consent prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.)

Who cannot join

  • Patients meeting any one of these exclusion criteria will be prohibited from participating in this study.
  • Received any previous treatment for AML
  • Diagnosed with APL-M3 or CBF-AML
  • Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting Induction therapy.
  • Received >200 mg/m2 equivalents of daunorubicin
  • Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #3 above)
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  • Have active central nervous system (CNS) leukemia
  • Have evidence of uncontrolled disseminated intravascular coagulation
  • Have an active, uncontrolled infection
  • Have other life-threatening illness
  • Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
  • Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
  • Are pregnant and/or nursing

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Sidney Kimmel Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Columbia University

    New York, New York, 10032

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Dose-escalation, Safety and Biomarker Prediction of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

The purpose of this Phase I study is to determine the safety and tolerability including the maximum dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML

Read the detailed description

Primary Objective:

  • To determine the safety and tolerability including the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML

Secondary Objectives:

  • To observe patients for any evidence of antileukemic activity of alvocidib plus 7+3 using the 2017 ELN response criteria
  • To establish the Recommended Phase 2 Dose (RP2D) for future studies with alvocidib in combination with 7+3

Exploratory Objective:

  • To assess levels of minimal residual disease (MRD) using standardized techniques (ie, multiparametric flow cytometry [MPFC] and next generation sequencing [NGS] and evaluate other potential biomarkers including, but not limited to, MCL-1 dependency.
Being tested
Alvocidib, Cytarabine, Daunorubicin
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • AlvocidibDrug

    IV bolus followed by IV infusion

  • CytarabineDrug

    continuous infusion

  • DaunorubicinDrug

    IV bolus

Study groups in NCT03298984
Study groupRoleWhat they receive
Alvocidib and Cytarabine/DaunorubicinExperimentalThe starting dose of alvocidib will be 20 mg/m2 as a 30-minute intravenous (IV) bolus followed by 30 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 of Induction. Patients will have a one day drug holiday (Day 4) before initiation of the 7+3 regimen. Beginning on Day 5, cytarabine will be administered as a 100 mg/m2/day continuous IV infusion for seven consecutive days (Days 5-11) plus daunorubicin administered at a dosage of 60 mg/m2 IV on Days 5-7.
Receives: Drug: Alvocidib; Drug: Cytarabine; Drug: Daunorubicin

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Alvocidib

    Determine the safety and tolerability including the maximum tolerated dose (MTD) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML

    Measured: During the first cycle

  2. Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) of Alvocidib

    Determine the safety and tolerability including dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML

    Measured: During the first cycle

Secondary outcomes (2)

  1. Antileukemic Activity of Alvocidib Plus 7+3 - Response to Treatment Based on 2017 ELN Response Criteria

    CR: Measurable residual disease is positive or unknown; BM blasts (bls) <5%; no circulating bls and bls w/ Auer rods; no extramedullary disease; ANC >1.0 x 109/L; platelets >100 x 109/L. CRMRD-: CR w/ negativity genetic marker. CRi: CR except residual neutropenia or thrombocytopenia. MLFS: BM bls <5%; no bls with Auer rods; no extramedullary disease; no hematologic recovery required. PR: all hematologic CR criteria; decrease (dec) BM bls % to 5-25%; dec pretreatment BM bls % by >50%. SD: no CRMRD-/CR/CRi/PR/MLFS; PD criteria not met. PD: increase (inc) BM bls % and/or inc absolute bls in blood: 50% inc BM bls over baseline (>15% point inc required in cases w/ <30% bls at baseline or persistent BM bls % of >70% over at least 3 months; without at least 100% improvement in ANC to absolute level [>0.5 x 109/L and/or platelet count to >50 x 109/L non-transfused); or >50% inc in peripheral bls to >25 x 109/L (in the absence of differentiation syndrome); or new extramedullary disease.

    Measured: Best response during duration of study

  2. Recommended Phase 2 Dose (RP2D) of Alvocidib in Combination With 7+3

    The dose at which < 1 of 6 patients experience a DLT during Cycle 1 with the next higher dose having at least 2 of 3 to 6 patients experiencing a DLT during Cycle 1

    Measured: During Cycle 1 beginning at 1st dose of study drug through Day 50 + or - 3 days

Timeline

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

  1. First posted2 Oct 2017
  2. Study start25 Sep 2017
  3. Primary completion20 Mar 2020
  4. Study completion20 Mar 2020

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03298984
Sponsor's protocol ID
TPI-ALV-101
Status last verified
Nov 2023
First submitted
27 Sep 2017
Last updated
15 Nov 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zeidner JF, Lee DJ, Frattini M, Fine GD, Costas J, Kolibaba K, Anthony SP, Bearss D, Smith BD. Phase I Study of Alvocidib Followed by 7+3 (Cytarabine + Daunorubicin) in Newly Diagnosed Acute Myeloid Leukemia. Clin Cancer Res. 2021 Jan 1;27(1):60-69. doi: 10.1158/1078-0432.CCR-20-2649. Epub 2020 Sep 30.

    PubMed 32998965

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alvocidib, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by Sumitomo Pharma America, Inc. at 3 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 12 inclusion and 13 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 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 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.

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 24 May 2021). 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?

Maximum Tolerated Dose (MTD) of Alvocidib (time frame: During the first cycle). 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 NCT03298984, which also lists 1 linked publication.

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 15 Nov 2023.

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