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LeukemiaPhase 1/2NCT02464657

Study of Idarubicin, Cytarabine, and Nivolumab in Patients With High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

A Phase 1/2 study testing Nivolumab, Idarubicin and Cytarabine in people with Leukemia and Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 goal of this clinical research study is to find the highest tolerable dose of nivolumab that can be give in combination with idarubicin and cytarabine in patients with MDS and AML. The safety and effectiveness of this drug combination will also be studied. This is an investigational study. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Idarubicin and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
Jul 2015to 7 May 2020
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

  • Diagnosis of 1) AML (WHO classification definition of >/= 20% blasts), or 2) high risk MDS (defined as the presence of 10% blasts).
  • Patients aged 18 to 60 years are eligible. Patients older than 60 who are deemed fit to receive intensive chemotherapy by the treating physician are eligible after discussion with the PI.
  • In the Phase I portion, patients with relapsed or refractory AML/MDS are also eligible, as per the treating physician's discretion.
  • For the Phase II portion of the study, patients must be chemo-naive, i.e. not have received any prior chemotherapy (except hydrea or one dose of ara-C </= 2g) for AML or MDS. They could have received hypomethylator agents, transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as apheresis or hydrea or one dose of ara-C </= 2g in order to safely control hyperleucocytosis prior to enrollment.
  • Serum biochemical values with the following limits unless considered due to leukemia: ---Creatinine </= 1.5 mg/dl --- total bilirubin </= 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder --- transaminases (SG PT) </= 2.5 x upper limit of normal (ULN).
  • Ability to take oral medication.
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  • Ability to understand and provide signed informed consent.
  • Baseline test of ejection fraction must be >/= 50%.
  • Performance status < 3, unless directly related to disease process as determined by the Principal Investigator.

Who cannot join

  • Subjects with APL.
  • Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results.
  • Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study. --- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. --- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab. --- Women must not be breastfeeding.
  • Continued:Men who are sexually active with WOCBP must use acceptable birth control methods. Acceptable birth control methods include: oral or injectable hormonal birth control, intrauterine devices(IUDS), and double barrier methods (for example a condom in combination with spermicide). Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • History of cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within past 3 months.
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  • Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Active clinically serious and uncontrolled infection > CTCAE Grade 2 uncontrolled with antibiotics.
  • Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  • Patients should be excluded if they are known to be positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
  • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of allergy to study drug components.
  • Prior immune checkpoint targeting drugs (e.g., anti PD1, and PDL1, anti-kir, anti CD137...etc)

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

Official title: Phase I/II Study of Idarubicin, Cytarabine, and Nivolumab in Patients With High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

The goal of this clinical research study is to find the highest tolerable dose of nivolumab that can be give in combination with idarubicin and cytarabine in patients with MDS and AML. The safety and effectiveness of this drug combination will also be studied.

This is an investigational study. Nivolumab is not FDA-approved or commercially available. Idarubicin is FDA-approved and commercially available for the treatment of patients with AML. Cytarabine is FDA approved and commercially available for treatment of patient with AML. The use of these drugs in combination is investigational. The study doctor can explain how the drugs are designed to work.

Up to 75 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 based on when you join this study. Up to 3 groups of 3 - 6 participants will be enrolled in Phase 1 of the study, and up to 70 participants will be enrolled in Phase 2.

If you are enrolled in Phase 1, the dose of nivolumab you receive will depend on when you join this study. There are 3 dose levels being tests in this part of the study: a low dose, a middle dose, and a high dose. The first group of participants will receive the middle dose level of nivolumab. If no intolerable side effects are seen, the next group will receive the highest dose level. However, if there are intolerable side effects, 3 more participants will receive the middle dose. If there are further intolerable side effects seen, the next group will receive the lowest dose of nivolumab.

If you are enrolled in Phase 2, you will receive nivolumab at the highest dose that was tolerated in Phase 1.

All participants will receive the same dose levels of idarubicin and cytarabine.

Study Drug Administration:

You will receive 1- 7 cycles of the drug combination. These cycles will be 28-35 days long.

  • On Days 1-3 of each cycle, you will receive idarubicin by vein over about 15-30 minutes.
  • On Days 1-4 of each cycle, you will receive cytarabine by vein over about 24 hours. If you are age 60 or older, you will receive the drugs on Days 1-3 only. On these days you will receive drugs to help decrease the risk of side effects.
  • On Day 24 (+/- 2 days) of each cycle, you will receive nivolumab by vein over about 1 hour.

After 2 cycles, if the disease appears to get better, you will receive nivolumab by vein about every 2 weeks for up to 1 year.

Study Visits:

At least one (1) time a week during Cycle 1 and then at least once each cycle after that:

  • You will have a physical exam.
  • Blood (about 2-3 teaspoons) will be drawn for routine tests.

You will have a bone marrow aspirate collected for cytogenetics testing between Day 21-28 of each cycle and then, if the doctor thinks it is needed, you will have this performed every 1-2 weeks after that unless a complete response is achieved. After that, you will have bone marrow collected every 3-6 months for 1 year.

After your last dose of study drug, you will have a physical exam.

Length of Study:

You may continue taking nivolumab for up to 1 year. 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.

Your participation on the study will be over after the follow-up visits.

Being tested
Nivolumab, Idarubicin, Cytarabine, Solu-medrol, Dexamethasone
Keywords
Leukemia, Acute myeloid leukemia, AML, Myelodysplastic Syndrome, MDS, High-risk, Nivolumab, BMS-936558, Opdivo, Idarubicin, Idamycin, Cytarabine, Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride, Solu-Medrol, Methylprednisolone, Depo-Medrol, Medrol
Medical subject headings
Leukemia, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

  • NivolumabDrug

    Also called BMS-936558, Opdivo

    Phase I Starting Dose of Nivolumab: 1 mg/kg by vein on Day 24 of a 28 day cycle.

    Phase II Starting Dose of Nivolumab: Maximum tolerated dose from Phase I.

  • IdarubicinDrug

    Also called Idamycin

    Phase I and Phase II dose of Idarubicin 12 mg/m2 by vein daily for 3 on Days 1 - 3 of a 28 day cycle.

  • CytarabineDrug

    Also called Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

    Phase I and Phase II dose of Cytarabine (Ara-C) 1.5 g/m2 by vein daily on Days 1 - 4 of a 28 day cycle.

  • Solu-medrolDrug

    Also called Methylprednisolone, Depo-Medrol, Medrol

    Phase I and Phase II dose of Solu-medrol 50 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.

  • DexamethasoneDrug

    Also called Decadron

    Phase I and Phase II dose of Dexamethasone 10 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.

Study groups in NCT02464657
Study groupRoleWhat they receive
Ph 1 Nivolumab (1mg) + Idarubicin + CytarabineExperimentalPhase I dose of Nivolumab 1 mg/kg by vein on Day 24 of a 28 day cycle. Phase I and Phase II dose of Idarubicin 12 mg/m2 by vein daily for 3 on Days 1 - 3 of a 28 day cycle. Phase I and Phase II dose of Cytarabine (Ara-C) 1.5 g/m2 by vein daily on Days 1 - 4 of a 28 day cycle. Phase I and Phase II dose of Solumedrol 50 mg or Dexamethasone 10 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.
Receives: Drug: Nivolumab; Drug: Idarubicin; Drug: Cytarabine; Drug: Solu-medrol; Drug: Dexamethasone
Ph 1 Nivolumab (3 mg) + Idarubicin + CytarabineExperimentalPhase I dose of Nivolumab 3 mg/kg by vein on Day 24 of a 28 day cycle. Phase I and Phase II dose of Idarubicin 12 mg/m2 by vein daily for 3 on Days 1 - 3 of a 28 day cycle. Phase I and Phase II dose of Cytarabine (Ara-C) 1.5 g/m2 by vein daily on Days 1 - 4 of a 28 day cycle. Phase I and Phase II dose of Solumedrol 50 mg or Dexamethasone 10 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.
Receives: Drug: Nivolumab; Drug: Idarubicin; Drug: Cytarabine; Drug: Solu-medrol; Drug: Dexamethasone
Ph 2 Nivolumab (3 mg) + Idarubicin + CytarabineExperimentalPhase II dose of Nivolumab 3 mg/kg by vein on Day 24 of a 28 day cycle. Phase I and Phase II dose of Idarubicin 12 mg/m2 by vein daily for 3 on Days 1 - 3 of a 28 day cycle. Phase I and Phase II dose of Cytarabine (Ara-C) 1.5 g/m2 by vein daily on Days 1 - 4 of a 28 day cycle. Phase I and Phase II dose of Solumedrol 50 mg or Dexamethasone 10 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.
Receives: Drug: Nivolumab; Drug: Idarubicin; Drug: Cytarabine; Drug: Solu-medrol; Drug: Dexamethasone

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Nivolumab

    MTD is highest dose level in which <2 patients of 6 develop first cycle dose-limiting toxicity (DLT).

    Measured: 28 days

Secondary outcomes (3)

  1. Event-Free Survival (EFS)

    EFS defined as time from the treatment start till treatment failure, relapse, or death whichever comes first. Event Free Survival will be presented by median EFS, which is the time point at which the cumulative survival drops below 50%. If there is no median survival (not reached), it means the cumulative survival was more than 50%.

    Measured: 56 days

  2. Relapse Free Survival

    Relapse-free survival was defined as the time from treatment response to date of relapse or death, whichever occurred first.

    Measured: Up to 2 years and10 Months

  3. Overall Survival

    Overall survival was defined as the time from the start of treatment to death or date of last follow-up.

    Measured: Up to 2 years and 10 Months

Timeline

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

  1. First posted8 Jun 2015 (estimated)
  2. Study startJul 2015
  3. Primary completion7 May 2020
  4. Study completion7 May 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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02464657
Sponsor's protocol ID
2014-0907
Other IDs
NCI-2015-01258
Status last verified
Sep 2021
First submitted
3 Jun 2015
Last updated
7 Oct 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ravandi F, Assi R, Daver N, Benton CB, Kadia T, Thompson PA, Borthakur G, Alvarado Y, Jabbour EJ, Konopleva M, Takahashi K, Kornblau S, DiNardo CD, Estrov Z, Flores W, Basu S, Allison J, Sharma P, Pierce S, Pike A, Cortes JE, Garcia-Manero G, Kantarjian HM. Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study. Lancet Haematol. 2019 Sep;6(9):e480-e488. doi: 10.1016/S2352-3026(19)30114-0. Epub 2019 Aug 7.

    PubMed 31400961

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab, Idarubicin and Cytarabine in people with Leukemia and Acute Myeloid 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 9 inclusion and 15 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 Oct 2021. 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 7 Oct 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 Nivolumab (time frame: 28 days). 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 NCT02464657, 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 7 Oct 2021.

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