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Recurrent Adult Acute Myeloid LeukemiaPhase 1NCT02070458

Ixazomib, Mitoxantrone Hydrochloride, Etoposide, and Intermediate-Dose Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing ixazomib, mitoxantrone hydrochloride and etoposide in people with Recurrent Adult Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Case Comprehensive Cancer Center 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 phase I trial studies the side effects and best dose of ixazomib when given in combination with mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine in treating patients with acute myeloid leukemia that is unresponsive to initial induction chemotherapy or recurs following an initial complete… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
ixazomib, mitoxantrone hydrochloride and etoposide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesUnited States
Study dates
8 Oct 2014to 15 Aug 2017
Phase
Phase 1
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
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  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Subjects with a prior diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization Classification who did not achieve complete response (CR) with their previous therapy or who have relapsed after achieving a complete response (CR) are eligible; any number of relapses will be eligible.
  • Patients must have > 5% blasts in the bone marrow at the time of study enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2, or 3
  • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN) within 14 days of enrollment
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN within 14 days of enrollment
  • Calculated creatinine clearance ≥ 30 mL/min within 14 days of enrollment
  • Patients with secondary AML, and patients with a prior autologous and allogeneic bone marrow transplant are eligible
  • Patients with an allogeneic transplant must meet the following conditions: the transplant must have been performed more than 90 days before registration to this study, the patient must not have ≥ grade 2 acute graft versus host disease (GvHD) or either moderate or severe limited chronic GvHD, or extensive chronic GvHD of any severity; the patient must be off all immunosuppression for at least 2 weeks
  • Echocardiogram or multi gated acquisition (MUGA) scan demonstrating an ejection fraction ≥ 45%

Who cannot join

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period
  • Failure to have fully recovered (i.e., ≤ grade 1 toxicity) from the reversible effects of prior chemotherapy, excluding alopecia
  • Major surgery within 14 days before enrollment
  • Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708
  • Central nervous system involvement; a lumbar puncture does not need to be performed unless there is clinical suspicion of leptomeningeal disease
  • Uncontrolled infections
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  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
  • Systemic treatment, within 3 days before the first dose of MLN9708, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
  • Ongoing or active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing
  • Patients with prior malignancy are eligible; however, the patient must be in remission from the prior malignancy and have completed all chemotherapy and radiotherapy at least 6 months prior to registration and all treatment-related toxicities must have resolved; patients with basal cell or squamous cell carcinoma of the skin are eligible regardless of disease status
  • Patient has ≥ grade 2 peripheral neuropathy within 14 days of trial enrollment
  • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial
  • Any standard therapy for leukemia within 14 days before enrollment (except for hydrea)
  • Patients who have received prior pulmonary radiation

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

  • University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: A Phase 1 Study of MLN9708 in Combination With MEC (Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine) for Relapsed/ Refractory Acute Myelogenous Leukemia (AML)

This phase I trial studies the side effects and best dose of ixazomib when given in combination with mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine in treating patients with acute myeloid leukemia that is unresponsive to initial induction chemotherapy or recurs following an initial complete remission. Acute myeloid leukemia is a cancer of the bone marrow cells; bone marrow is where blood cells are normally made. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine are standard treatment for relapsed or refractory acute myeloid leukemia. Giving ixazomib with mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine may improve the effectiveness of the chemotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and the recommended Phase 2 dose of MLN9708 (ixazomib) in combination with mitoxantrone hydrochloride, etoposide, intermediate-dose cytarabine (MEC) in patients with relapsed/ refractory acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

  1. To describe the non-dose limiting toxicities associated with MLN9708 in combination with MEC in patients with relapsed/ refractory AML.

II. To describe any preliminary evidence of clinical activity of this combination (compete response [CR] rate) in relapsed/ refractory AML.

III. To determine the median cluster of differentiation (CD)74 antigen expression in patients achieving a response versus those patients not achieving a response.

IV. To determine if gene expression profile pre- and post-treatment correlates with response to therapy.

OUTLINE: This is a dose-escalation study of ixazomib.

Patients receive ixazomib orally (PO) on days 1, 4, 8, and 11, mitoxantrone hydrochloride intravenously (IV), etoposide IV over 1 hour, and intermediate-dose cytarabine IV over 6 hours on days 1-6.

After completion of study treatment, patients are followed up for 4-5 weeks.

Being tested
ixazomib, mitoxantrone hydrochloride, etoposide, cytarabine
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.

  • ixazomibDrug

    Also called MLN9708, proteasome inhibitor MLN9708

    Given PO

  • mitoxantrone hydrochlorideDrug

    Also called CL 232315, DHAD, DHAQ, Novantrone

    Given IV

  • etoposideDrug

    Also called EPEG, VP-16, VP-16-213

    Given IV

  • cytarabineDrug

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

    Given IV

Study groups in NCT02070458
Study groupRoleWhat they receive
Treatment (ixazomib, MEC)ExperimentalPatients receive ixazomib PO on days 1, 4, 8, and 11; they receive mitoxantrone hydrochloride IV, etoposide IV over 1 hour; the receive intermediate-dose cytarabine IV over 6 hours on days 1-6.
Receives: Drug: ixazomib; Drug: mitoxantrone hydrochloride; Drug: etoposide; Drug: cytarabine

What is being measured

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

  1. DLT assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) scale version 4.03

    Measured: Up to 5 weeks

  2. MTD of ixazomib in combination with MEC based on the occurrence of DLT assessed using NCI CTC scale version 4.03

    Measured: Up to 5 weeks

  3. Recommended Phase 2 dose

    Measured: Up to 5 weeks

Secondary outcomes (5)

  1. Incidence of non-DLT assessed using NCI CTC scale version 4.03

    Measured: Up to 5 weeks

  2. Complete response (CR) rate

    The CR rate in this population will be evaluated and explored in a preliminary manner given the small number of patients and different dose levels. The Cheson criteria will be used to analyze response.

    Measured: Up to 5 weeks

  3. Complete remission with incomplete platelet recovery (CRp) rate

    The CRp rate in this population will be evaluated and explored in a preliminary manner given the small number of patients and different dose levels. The Cheson criteria will be used to analyze response.

    Measured: Up to 5 weeks

  4. Gene expression profile analysis

    Gene expression profiles will be summarized and compared in patients with response (CR/ CRp) versus patients with no response (all others).

    Measured: Up to 5 weeks

  5. CD74 antigen expression expression analysis

    The CD74 antigen expression will be summarized and compared in patients with response (CR/ CRp) versus patients with no response (all others).

    Measured: Up to 5 weeks

Timeline

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

  1. First posted25 Feb 2014 (estimated)
  2. Study start8 Oct 2014
  3. Primary completion17 Mar 2017
  4. Study completion15 Aug 2017

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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02070458
Sponsor's protocol ID
CASE7913
Other IDs
NCI-2014-00371, X16014_MLN9708, CASE7913, P30CA043703
Status last verified
Dec 2018
First submitted
21 Feb 2014
Last updated
13 Dec 2018
Results posted
No
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 study testing ixazomib, mitoxantrone hydrochloride and etoposide in people with Recurrent Adult Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Case Comprehensive Cancer Center 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 20 inclusion and 17 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 13 Dec 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 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?

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 assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) scale version 4.03 (time frame: Up to 5 weeks). The study lists 3 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 NCT02070458.

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 13 Dec 2018; AzTrials last refreshed its copy on 7 Nov 2026.

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