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Adult Acute Megakaryoblastic Leukemia (M7)Phase 1NCT01127009

Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing bortezomib, mitoxantrone hydrochloride and etoposide in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Case Comprehensive 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

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone, etoposide, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
bortezomib, mitoxantrone hydrochloride and etoposide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
Jul 2010to May 2014
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 informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study; female subject is not lactating
  • Male subject agrees to use an acceptable method for contraception for the duration of the study
  • Relapsed or refractory AML (excluding acute promyelocytic leukemia), based on World Health Organization Classification; all other subtypes of AML will be eligible; refractory disease will be considered failure to respond to 2 cycles of induction chemotherapy (7+3 and 5+2); any number of relapses will be eligible
  • No evidence of leptomeningeal disease; a lumbar puncture does not need to be performed unless there is clinical suspicion of leptomeningeal disease
  • Previous treatment related toxicities must have resolved to Grade 1 (excluding alopecia)
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  • Liver enzymes (AST and ALT) can not be greater than 2.5 times the upper limits of normal (ULN), and total bilirubin =< 1.5 x ULN within 14 days of enrollment
  • Renal function: Serum creatinine should be =< 1.5 x ULN within 14 days of enrollment
  • No serious or poorly controlled medical conditions that could be exacerbated by treatment or that would seriously complicate compliance with the protocol
  • ECOG performance status 0-3
  • No peripheral neuropathy >= Grade 2 within 14 days of trial enrollment
  • Echocardiogram or MUGAs scan demonstrating an ejection fraction >= 45%
  • 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
  • No uncontrolled infections
  • No history of hypersensitivity to boron or mannitol
  • No known history of HIV or active hepatitis B or C
  • No major surgery within 4 weeks prior to trial enrollment

Who cannot join

  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant
  • Patient has >= Grade 2 peripheral neuropathy within 14 days before enrollment
  • Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Patient has received any standard or investigational therapy for their leukemia within 14 days before enrollment (except for hydrea)
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • 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
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  • Leptomeningeal/ central nervous system involvement with AML; a lumbar puncture does not need to be performed unless there is clinical suspicion
  • Patients who have had prior pulmonary radiation
  • Prohibited Concurrent Therapy: any investigational agent other than VELCADE; G-CSF and GM-CSF are not allowed

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

Other trials in United States

About this study

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

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone, etoposide, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with mitoxantrone, etoposide, and cytarabine in treating patients with relapsed or refractory acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the DLT, MTD, and the recommended Phase 2 dose of bortezomib in combination with MEC in patients with relapsed/refractory AML.

SECONDARY OBJECTIVES:

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

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

III. To determine the median CD74 antigen expression in patients achieving a response versus those patients not achieving a response.

OUTLINE:

This is a dose-escalation study of bortezomib.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8 and 11; and mitoxantrone IV, etoposide IV over 1 hour, and intermediate-dose cytarabine IV over 6 hours on days 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.

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

Being tested
bortezomib, mitoxantrone hydrochloride, etoposide, cytarabine, flow cytometry
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

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

  • bortezomibDrug

    Also called LDP 341, MLN341, PS-341, VELCADE

    Given IV

  • mitoxantrone hydrochlorideDrug

    Also called CL 232315, DHAD, DHAQ, dihydroxyanthracenedione

    Given IV

  • etoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, epipodophyllotoxin, VePesid

    Given IV

  • cytarabineDrug

    Also called ARA-C, ARA-cell, arabinofuranosylcytosine, arabinosylcytosine

    Given IV

  • flow cytometryOther

    Correlative studies

Study groups in NCT01127009
Study groupRoleWhat they receive
Arm IExperimentalPatients receive bortezomib IV over 3-5 seconds on days 1, 4, 8 and 11; and mitoxantrone IV, etoposide IV over 1 hour, and intermediate-dose cytarabine IV over 6 hours on days 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: bortezomib; Drug: mitoxantrone hydrochloride; Drug: etoposide; Drug: cytarabine; Other: flow cytometry

What is being measured

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

  1. MTD of bortezomib

    Measured: two times a week until Day 28, then every week until Day 45 (+/- 2 days), then 4 wks after treatment.

Secondary outcomes (3)

  1. Non-dose limiting toxicities

    Measured: two times a week until Day 28, then every week until Day 45 (+/- 2 days), then 4 wks after treatment.

  2. CR/ CRp rate

    Measured: repeated 4 weeks after the post-treatment bone marrow aspirate/biopsy.

  3. CD74 antigen expression

    Measured: to be performed only on the pre-treatment sample

Timeline

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

  1. First posted20 May 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionMay 2014
  4. Study completionMay 2014

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01127009
Sponsor's protocol ID
CASE4909
Other IDs
NCI-2010-01203, CASE4909
Status last verified
Aug 2015
First submitted
19 May 2010
Last updated
13 Aug 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib, mitoxantrone hydrochloride and etoposide in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Case Comprehensive 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 18 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 13 Aug 2015. 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 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?

MTD of bortezomib (time frame: two times a week until Day 28, then every week until Day 45 (+/- 2 days), then 4 wks after treatment.). 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 NCT01127009.

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 Aug 2015.

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