AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1/2NCT01606579

Safety and Efficacy Study of PRI-724 in Subjects With Advanced Myeloid Malignancies

A Phase 1/2 study testing PRI-724 in people with Acute Myeloid Leukemia and Chronic Myeloid Leukemia, run by Prism Pharma Co., Ltd. at 6 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

PRI-724 is a new investigational drug being studied to treat subjects with cancer who have advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling pathway that cancer cells need to grow and spread (metastasize). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PRI-724
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
6 sitesUnited States
Study dates
Jul 2012to 30 Dec 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Patients 18 years or older
  • Part I: Patients with one of the following histologically- or cytologically-proven conditions: relapsed/refractory AML, relapsed/refractory MDS, or advanced CML in AP or BP (i.e., Acute Group patients).
  • Part II: Patients with one of the following documented conditions: CML in CP that is Philadelphia chromosome (Ph)-positive (by cytogenetics) or BCR-ABL1-positive by fluorescent in situ hybridization [FISH], or PCR), as well as resistant to at least 2 FDA-approved tyrosine kinase inhibitors (TKIs); or a myeloproliferative neoplasia which includes: PMF and myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) myelofibrosis (MF) (with intermediate-1, intermediate-2 or high risk disease according to the International Working Group [IWG] prognostic scoring system) (i.e., Non-Acute Group patients).
  • Part III:
  • Arm A: Patients with AML who are 65 years of age or older with refractory or relapsed disease, or who have not received prior therapy but are not eligible to receive intensive frontline chemotherapy (i.e., Acute Group patients);
  • Arm B: Patients with CML in AP or BP, either newly diagnosed or failing TKI therapy (i.e., Acute Group patients);
Show all 15Show fewer
  • Arm C: Patients with CML in CP after failure of 2 FDA-approved TKIs (i.e., Non-Acute group patients)
  • Performance status 0-2 of the Eastern Cooperative Oncology Group (ECOG) scale
  • Patients must have been off all prior therapy for leukemia except hydroxyurea for 1 week prior to entering this study and recovered from the toxic effects of that therapy
  • Adequate organ function as defined by:
  • Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥60 mL/min
  • Total bilirubin ≤2 x ULN (≤5 x ULN if considered due to Gilbert's syndrome or hemolysis)
  • Alanine aminotransferase (ALT) ≤3xULN
  • Patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
  • Women of childbearing potential and men should practice effective methods of contraception. Women of childbearing potential should have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin within 7 days prior to the start of PRI 724.

Who cannot join

  • Patients receiving any other investigational agents
  • Patients who are pregnant or breast-feeding
  • Known hypersensitivity to any of the components of PRI-724
  • Pretreatment QTcF interval >470 msec (females) or >450 msec (males)
  • Known active hepatitis B, hepatitis C
  • Serious uncontrolled medical disorder or active systemic infection or current unstable or decompensated medical condition, which makes it undesirable or unsafe for the patient to participate in the study including: New York Heart Association (NYHA) Class 3 or 4, myocardial infarction within 3 months, uncontrolled angina within 3 months, history of clinically significant ventricular arrhythmia, diabetes mellitus with ketoacidosis, or chronic obstructive pulmonary disease (COPD) requiring hospitalization in 6 months prior to the start of treatment with PRI-724.
Show all 9Show fewer
  • Any other condition, including mental illness or substance abuse deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate, and participate in the study
  • Patients on full dose anticoagulants or any dose of warfarin; patients on prophylactic dose of low-molecular weight or unfractionated heparin are allowed.
  • Patients who have demonstrated intolerance to dasatinib 100 mg daily will not be eligible for Part III/Arm B or C of the study.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • New Mexico Cancer Care Alliance

    Albuquerque, New Mexico, 87106

  • Emory University / Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Ohio State University

    Columbus, Ohio, 43210-1267

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77030

  • University of Massachusetts Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: An Open-Label, Dose-Escalation Phase I/II Study of PRI-724 for Patients With Advanced Myeloid Malignancies

PRI-724 is a new investigational drug being studied to treat subjects with cancer who have advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling pathway that cancer cells need to grow and spread (metastasize).

Read the detailed description

PRI-724 is a new investigational drug being studied to treat subjects with cancer who have advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling pathway that cancer cells need to grow and spread (metastasize).

Purpose:

  • To test the safety of PRI-724 when taken intravenously (through the vein).
  • To observe whether PRI-724 can slow or stop the progression of leukemia.
  • To find the Maximum Tolerated Dose (highest safe dose) in the first two parts of the study.
  • To find the dose of PRI-724 that should be used in the third part of the study and possible future clinical trials that will study effectiveness and additional safety.
  • To test the safety of combining PRI-724 with an approved cancer drug called dasatinib in treating chronic myeloid leukemia (CML).
  • To evaluate whether the combination of PRI-724 with the approved cancer drug dasatinib slows or stops the progression of chronic myeloid leukemia (CML).
  • To test the safety of combining PRI-724 with an approved cancer drug called Cytarabine in treating acute myelogenous leukemia (AML).
  • To evaluate whether the combination of PRI-724 with the approved cancer drug Cytarabine slows or stops the progression of acute myelogenous leukemia (AML).
  • To measure how much PRI-724 appears and remains in the blood after infusion.
  • To measure several signals called biomarkers associated with cancer in the blood to see if PRI-724 affects those signals.

Study Design:

This will be a single center, open-label escalating-dose cohort study with 3 parts: Part I during which the MTD will be determined in acute group patients; Part II during which the MTD will be determined in non-acute group patients; and Part III during which safety and tolerability of escalating doses of PRI-724 will be assessed in combination with dasatinib for CML patients or low dose ara-C therapy for AML patients ≥ 65 years of age.

Being tested
PRI-724
Keywords
Leukemia, acute myeloid leukemia, AML, chronic myeloid leukemia, CML, MDS, myelodysplastic syndrome, myeloproliferative neoplasia, MPN
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelodysplastic Syndromes

What participants receive

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

  • PRI-724Drug

    PRI-724

  • PRI-724Drug

    PRI-724 in combination with dasatinib

  • PRI-724Drug

    PRI-724 in combination with low dose ara-C therapy

Study groups in NCT01606579
Study groupRoleWhat they receive
Part IExperimentalSingle-agent MTD (or maximum dose to be studied) of PRI-724 will be determined in escalating dose cohorts of Acute Group patients. The MTD cohort will be expanded up to 10 patients to further evaluate tolerability.
Receives: Drug: PRI-724
Part IIExperimentalSingle-agent MTD (or maximum dose to be studied) of PRI-724 will be determined in escalating dose cohorts of Non-Acute Group patients. Dosing will begin 2 dose levels below the Part I MTD. The MTD cohort will be expanded up to 10 patients to further evaluate tolerability.
Receives: Drug: PRI-724
Part III Arm AExperimentalOnce the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each. Escalating doses of PRI-724, beginning 2 dose levels below the Part I MTD will be administered in combination with low dose ara-C therapy (20 mg SC BID × 10d q 28d) for AML patients ≥ 65 years of age.
Receives: Drug: PRI-724
Part III Arm BExperimentalOnce the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each. Escalating doses of PRI-724, beginning 2 dose levels below the Part I MTD will be administered in combination with dasatinib (140 mg PO daily) to Acute Group patients with CML-AP or BC.
Receives: Drug: PRI-724
Part III Arm CExperimentalOnce the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each. Escalating doses of PRI-724, beginning 1 dose level below the Part II MTD will be administered in combination with dasatinib (100 mg PO daily) to Non-Acute Group patients with CML-CP.
Receives: Drug: PRI-724

What is being measured

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

  1. DLT (Dose Limiting Toxicity)

    Observance of 1 DLT in first 3 patients during 3+3 phase will result in the enrollment of an additional 3 patients.

    Observance of 2+ DLTs in 6 patients during 3+3 phase will result in the next lower dose being expanded.

    Observance of DLTs in 33% of patients in 10 patient MTD expansion will result in the next lower dose being expanded.

    MTD will only be established in a dose level where 0/3 pts or 1/6 pts have a DLT observed in first 2 cycles of therapy.

    Two types of DLTs will be observed: non-hematologic and hematologic.

    Measured: 1 year

Secondary outcomes (1)

  1. Preliminary Efficacy Endpoints

    The preliminary efficacy endpoints will be changes in the response assessment according to International Working Group Response Criteria for Acute Myeloid Leukemia (AML), European LeukemiaNet Response Criteria for Chronic Myeloid Leukemia (CML), International Working Group Response Criteria for Myelodysplastic Syndromes (MDS) and International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia

    Measured: 1 year

Timeline

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

  1. First posted25 May 2012 (estimated)
  2. Study startJul 2012
  3. Primary completion30 Dec 2016
  4. Study completion30 Dec 2016

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
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01606579
Sponsor's protocol ID
PRI-724-201
Status last verified
May 2017
First submitted
16 May 2012
Last updated
17 Aug 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PRI-724 in people with Acute Myeloid Leukemia and Chronic Myeloid Leukemia, run by Prism Pharma Co., Ltd. at 6 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 15 inclusion and 9 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 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

DLT (Dose Limiting Toxicity) (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 NCT01606579.

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 17 Aug 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in