AzTrials
AzTrials

LeukemiaPhase 1/2NCT01498445

An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)

A Phase 1/2 study testing Dasatinib and Decitabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The goal of this clinical research study is to learn if combining Sprycel (dasatinib) and Dacogen (decitabine) can help to control Chronic Myeloid Leukemia (CML). The dose level of decitabine will also be studied. Dasatinib is designed to block the protein that is responsible for chronic myeloid leukemia. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Dasatinib and Decitabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
12 Jun 2012to 24 Sep 2019
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients age 18 years of age or older with CML-AP, CML-BP or Philadelphia chromosome-positive acute myeloid leukemia defined as follows: CML-AP is defined by the presence of 15-29% blasts in peripheral blood (PB) or bone marrow (BM), >/= 20% basophils in PB or BM, >/= 30% blasts plus promyelocytes (with blasts <30%) in PB or BM, <100 x10(9)/L platelets unrelated to therapy, or by clonal cytogenetics evolution (i.e., the presence of cytogenetic abnormalities other than the Philadelphia chromosome); CML-BP is defined by the presence of >/= 30% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease.
  • Patients are eligible whether they have received or not prior TKI therapy. For the phase I portion of the study, patients who had received prior therapy with dasatinib should have been able to tolerate the dose equivalent to the starting dose of dasatinib in the dose level at which the patient is being entered. Patients who previously received dasatinib but never at the dose being proposed are eligible provided they tolerated the maximum dose they were prescribed with no grade 3-4 toxicity not responding to optimal management.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
  • Men and women of childbearing potential should practice 2 methods of contraception; 1 method must be highly effective and a second method must be either highly effective or less effective. Men and women of childbearing potential are defined as: a male that has not been surgically sterilized or a female that has not been amenorrheic for at least 12 consecutive months or that has not been surgically sterilized. Patients must use birth control during the study and for 3 months after the last dose of study drug if they are sexually active.
  • Women of childbearing potential must have a pregnancy test at screening.
  • Signed informed consent.
  • Patients must have been off all prior therapy for CML for 2 weeks prior to start of study therapy and recovered from the toxic effects of that therapy. Exceptions to these are hydroxyurea and Tyrosine kinase inhibitor (TKIs) (including but not limited to imatinib, nilotinib, and bosutinib) which should be discontinued >/= 24 hrs prior to the start of therapy. Patients who are receiving dasatinib prior to enrollment do not have to discontinue this agent prior to start of study therapy.
  • Adequate organ function: Serum creatinine </= 2.0 mg/dl or creatinine clearance >/=60 mL/min; Total bilirubin </= 1.5 x upper limit of normal (ULN) (unless considered due to Gilbert's syndrome or hemolysis); Alanine aminotransferase (ALT) </= 3 x ULN unless considered due to leukemic involvement.

Who cannot join

  • New York Heart Association (NYHA) cardiac class 3-4 heart disease.
  • Cardiac disease including: Uncontrolled angina within 3 months. Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) on the Fridericia's correction; Uncontrolled hypertension (defined for this protocol as sustained systolic BP >/=150 and diastolic >/=100); Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes.
  • Serious uncontrolled medical disorder or uncontrolled active systemic infection or current unstable or decompensated respiratory or cardiac conditions which makes it undesirable or unsafe for the patient to participate in the study.
  • Patients with known, clinically significant pericardial or pleural effusion.
  • History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), or diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies).
  • Subject is receiving potent inhibitors of CYP3A4; for such medications, a wash-out period of >/= 7 days is required prior to starting dasatinib unless discontinuation or substitution of such an inhibitor is not in the best interest of the patient as determined by the investigator. These include the following medications: itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, isoniazid, ketamine, nefazodone, nicardipine, propofol, quinidine, telithromycin. In instances where use of these agents is felt to be required for the best management of the patients, inclusion of such a patients should be discussed with PI and the rationale documented.
  • Females who are pregnant or are currently breastfeeding.
  • Patients that are eligible (including having available donor) and willing to receive an allogeneic stem cell transplant within 4 weeks.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

The goal of this clinical research study is to learn if combining Sprycel (dasatinib) and Dacogen (decitabine) can help to control Chronic Myeloid Leukemia (CML). The dose level of decitabine will also be studied.

Dasatinib is designed to block the protein that is responsible for chronic myeloid leukemia.

Read more

Decitabine is designed to affect the mechanism that cells use to control the expression of certain genes, some of which are important in the progression of CML.

This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of patients with certain types of CML.

Decitabine is FDA approved for the treatment of patients with myelodysplastic syndrome.

The combination of these drugs to treat CML is investigational.

Up to 84 patients will take part in this study. All will be enrolled at MD Anderson.

Read the detailed description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group and dose level based on when you join this study and the side effects that are seen. Your doctor will discuss this with you in more detail.

There will be up to 5 doses of dasatinib tested in Phase 1. The first 3 participants will receive a lower dose of therapy. If no major side effects are seen in these participants, the next participants will receive a higher dose. Once a dose is identified that is well-tolerated for most participants, that dose will be used for all new participants. If you are in Phase 2, you will receive a dose level tested in Phase 1.

You will receive one of 2 doses of decitabine. What dose you receive is determined by chance (like a coin toss).

Study Administration:

Each cycle is 28 days.

You will take dasatinib by mouth 1 time a day.

You will receive decitabine by vein for 10 days of each cycle. If the doctor thinks it is in your best interest, you may receive decitabine for fewer days each cycle (5 days instead of 10 days). Your doctor will decide how many doses you will take based on side effects you may have and the status of the disease.

If you have severe side effects from the study drug, the study doctor may decide to stop drug dosing until your side effects improve.

You will be asked to keep a study diary that will be reviewed at scheduled study visits. In the diary, you will record when you take the study drug.

Study Visits:

At every visit, you will be asked about any side effects you may have had and to list any drugs you may be taking.

Every week for the first 3 cycles and then every 2-4 weeks after that, blood (about 1 tablespoon) will be drawn to check your blood cell counts.

About 1 week after your first dose, you will have an ECG.

Every 1-2 weeks for the first 3 cycles and then every 4-8 weeks after that, blood (about 1 tablespoon) will be drawn to test your kidney and liver function.

Every 1-3 months, blood (about 1 tablespoon) will be drawn for genetic testing.

Before the start of Cycle 2, every 2-4 cycles after that for the first year, and then every 6 cycles after that, you will have a complete physical exam.

Before the start of Cycle 2, every 3 cycles after that during the first year, then every 4-6 cycles (as needed) you will have a bone marrow aspirate to check the status of the disease.

After Cycle 6, the number of blood draws and bone marrow collections may be changed.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Conditions
Leukemia
Being tested
Dasatinib, Decitabine
Keywords
Leukemia, Chronic myelogenous leukemia, Chronic myeloid leukemia, CML, Accelerated phase, Blastic phase, Dasatinib, BMS-354825, Sprycel, Decitabine, Dacogen
Medical subject headings
Leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Blast Crisis

What participants receive

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

  • DasatinibDrug

    Also called BMS-354825, Sprycel

    Starting Dose: 100 mg by mouth once daily of a 28 day cycle.

  • DecitabineDrug

    Also called Dacogen

    Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.

  • DecitabineDrug

    Also called Dacogen

    Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.

Study groups in NCT01498445
Study groupRoleWhat they receive
Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2ExperimentalLess Intensive, Schedule A1 Dasatinib 100 mg daily by mouth ; Decitabine 10 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.
Receives: Drug: Dasatinib; Drug: Decitabine
Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2ExperimentalMore Intensive, Schedule A2: Dasatinib 100 mg daily by mouth ; Decitabine ose 20 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.
Receives: Drug: Dasatinib; Drug: Decitabine
Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2ExperimentalLess Intensive, Schedule B1 Dasatinib 140 mg daily by mouth ; Decitabine 10 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.
Receives: Drug: Dasatinib; Drug: Decitabine
Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2ExperimentalMore Intensive, Schedule B2 Dasatinib 140 mg daily by mouth ; Decitabine 20 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.
Receives: Drug: Dasatinib; Drug: Decitabine
Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2ExperimentalLess Intensive, Schedule B1 Dasatinib 140 mg daily by mouth; Decitabine e 10 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.
Receives: Drug: Dasatinib; Drug: Decitabine
Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2ExperimentalMore Intensive, Schedule B2 Dasatinib140 mg daily by mouth; Decitabine 20 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.
Receives: Drug: Dasatinib; Drug: Decitabine

What is being measured

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

  1. Ph I Study: Maximum Tolerated Dose (MTD) Dasatinib

    Maximum tolerated dose (MTD) defined as highest dose at which 0 of 3 or </= 1/6 participant experience a first cycle dose limiting toxicity (DLT).

    Measured: End of first 28-day cycle

Secondary outcomes (3)

  1. Number of Participants With Hematologic Responses During First 3 Months of Treatment

    Number of participants with hematologic response (HR) to therapy during first 3 months of combination dasatinib and decitabine therapy, where HR defined as any hematologic response observed during the first 3 months of treatment. Overall Hematologic Response (OHR) is defined as complete hematologic response (CHR), no evidence of leukemia (NEL) or minor hematologic response (MiHR)

    Measured: 3 months

  2. Overall Survival

    Overall Survival will be measured from the date treatment is started to the date of death or last follow-up.

    Measured: Up to seven years

  3. Duration of Response

    Duration of Response will be measured from the date the given response is achieved to the date the response is first known to be lost

    Measured: up to seven years

Timeline

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

  1. First posted23 Dec 2011 (estimated)
  2. Study start12 Jun 2012
  3. Primary completion24 Sep 2019
  4. Study completion24 Sep 2019

Why it stopped: The study was terminated early during the phase II portion of the study due to slow enrollment.

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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01498445
Sponsor's protocol ID
2011-0333
Other IDs
CA180357, NCI-2012-00014
Status last verified
Sep 2020
First submitted
21 Dec 2011
Last updated
22 Oct 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dasatinib and Decitabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 8 inclusion and 8 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: stopped early, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 22 Oct 2020). 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?

Ph I Study: Maximum Tolerated Dose (MTD) Dasatinib (time frame: End of first 28-day cycle). 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 NCT01498445.

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 22 Oct 2020.

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