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Acute Lymphoblastic LeukemiaPhase 2NCT01312818

Bortezomib, Vorinostat and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

A Phase 2 study testing Bortezomib, Vorinostat and Dexamethasone in people with Acute Lymphoblastic Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Terminated

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

Official record
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Trial summary

Both of bortezomib and vorinostat have identified Phase II doses for pediatric and adult patients of which no grade 4 dose limiting toxicities have been observed in prior studies. Read more about this study

Who is it for?
Ages 2 to 30 years
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
Bortezomib, Vorinostat and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
Jun 2011to Jan 2013
Phase
Phase 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 2 to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis of lymphoblastic lymphoma or acute lymphoblastic leukemia (ALL) with ≥ 5% blasts in the bone marrow (M2/M3) with or without extramedullary disease that meets one of the following criteria:
  • Refractory Disease/Induction Failure: Failure to achieve initial remission after 2 attempts of standard induction therapy
  • Relapsed Disease: Patients in relapse #1 or higher for whom standard curative therapies or therapies to prolong survival do not exist.
  • Patients who are Philadelphia chromosome-positive (Ph + ALL) are eligible provided they are not imatinib resistant or intolerant.
  • Patients with CNS positive disease will be eligible.
  • Age 2 to 30 years
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  • Karnofsky ≥ 50% for patients 16 years and older and Lansky status ≥ 50 for patients under 16 years of age.
  • Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling investigator.
  • Have acceptable organ function as defined within 7 days of starting treatment:
  • Renal: creatinine clearance ≥ 70ml/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum serum creatinine (mg/dl) 0.8 for 2 years to <6 years; 1.0 for 6 years to <10 years; 1.2 for 10 years to <13 years; 1.5 male and 1.4 female for 13 years to <16 years; 1.7 male and 1.4 female for ≥ 16 years
  • Hepatic: ALT < 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5x upper limit of normal (ULN) for age.
  • Cardiac: left ventricular ejection fraction ≥ 40% by echocardiogram/multi gated acquisition scan (ECHO/MUGA). Normal QTc on electrocardiogram (EKG) (not to exceed upper limit of normal - men: 430 milliseconds (ms); women: 450 ms; children up to 15 years: 440 ms).
  • Prior Therapy:
  • Patients must have recovered from the non-hematologic toxic effects of all prior therapy before entry onto this trial. Recovery is defined as a Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 toxicity grade <2, unless otherwise specified in the Inclusion and Exclusion Criteria.
  • Cytotoxic therapy: Patients must have had their last dose of chemotherapy at least two weeks prior to study entry.
  • Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.
  • Biologic (anti-neoplastic) therapy: At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
  • Monoclonal antibodies: At least 3 half-lives of the antibody after the last administration of a monoclonal antibody.
  • Hematopoietic Stem Cell Transplant (HSCT): Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of Graft-versus-Host Disease (GVHD).
  • Women of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the last dose of chemotherapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the last dose of chemotherapy.
  • Voluntary written 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/guardian at any time without prejudice to future medical care.

Who cannot join

  • Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. 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 surgically sterilized women.
  • Known hypersensitivity to bortezomib, boron or mannitol or any of the agents or their ingredients used in this study.
  • Inability to swallow capsules.
  • Grade 2 or greater peripheral neuropathy within 14 days before study registration.
  • Patients with untreated positive blood cultures or progressive infections as assessed by radiographic studies.
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (appendix VI), 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.
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  • Serious concomitant medical or psychiatric disorders (e.g., active infection, uncontrolled diabetes) that, in the opinion of the investigator, would compromise the safety of the patient or likely to interfere with participation in this clinical study.
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
  • Patient has received investigational drugs within the 14 days before study registration.
  • Radiation therapy within 3 weeks before registration. Enrollment of patients who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center, University if Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: A Therapeutic Trial of Bortezomib (Velcade), Vorinostat (SAHA) and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

Both of bortezomib and vorinostat have identified Phase II doses for pediatric and adult patients of which no grade 4 dose limiting toxicities have been observed in prior studies. The pre-clinical synergy of these 2 agents when used in combination along with the lack of over-riding toxicities and different mechanisms of action provide strong rationale for a clinical trial investigating bortezomib and vorinostat in combination. This trial will use the identified Phase II dose which is at or below the maximum tolerated dose for both agents which have very acceptable toxicity profiles and such should prove feasible and tolerable in this relapsed/refractory ALL population.

Read the detailed description

This is a phase II study of bortezomib 1.3 mg/m^2 by intravenous pyelogram (IVP) on days 1, 4, 8, and 11, vorinostat 180 mg/m^2 by mouth (PO) per day (not to exceed 400 mg per day) days 1-14, and dexamethasone 6 mg/m^2 PO days 4-15 for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). No more than 3 treatment courses may be given.

Being tested
Bortezomib, Vorinostat, Dexamethasone, Methotrexate, Imatinib mesylate
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • BortezomibDrug

    Also called Velcade(R)

    1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.

  • VorinostatDrug

    Also called suberoylanilide hydroxamic acid (SAHA), Zolinza

    180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14

  • DexamethasoneDrug

    Also called Decadron

    6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.

  • MethotrexateDrug

    Also called Trexall, amethopterin

    Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)

  • Imatinib mesylateDrug

    Also called Gleevec(R)

    For Ph+ acute lymphoblastic leukemia (ALL) patients only:

    Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for >18 years on Days 1-16.

Study groups in NCT01312818
Study groupRoleWhat they receive
ChemotherapyExperimentalBortezomib IV Vorinostat PO Dexamethasone PO Intrathecal Methotrexate Imatinib Mesylate PO (for Ph+ ALL patients only)
Receives: Drug: Bortezomib; Drug: Vorinostat; Drug: Dexamethasone; Drug: Methotrexate; Drug: Imatinib mesylate

What is being measured

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

  1. Number of Subjects Who Achieved Complete Remission of Their Disease

    Complete Remission (CR): A CR requires that the following be recorded concurrently: an absolute neutrophil count (segs and bands) > 1000/μL, no circulating blasts, platelets > 100,000/μL; adequate bone marrow cellularity with trilineage hematopoiesis, and < 5% marrow leukemia blast cells. All previous extramedullary manifestations of disease must be absent. If patients continue on with treatment, there can be no evidence of recurrence of ALL for at least 4 weeks.

    Measured: Day 30

Secondary outcomes (2)

  1. Number of Subjects Experiencing Drug Related Adverse Events

    To characterize the toxicities of bortezomib, vorinostat and dexamethasone when used in combination. Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 4.0).

    Measured: Day 1 of Treatment to 30 Days Post Treatment

  2. Number of Subjects With Activated Caspases and Other Regulators of Apoptosis

    Activation of caspases and other regulators of apoptosis in treated blast cells will be determined by Western analysis (correlative lab analysis).

    Measured: From Day 1 to 30 Days After Last Dose

Timeline

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

  1. First posted11 Mar 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionJan 2013
  4. Study completionJan 2013

Why it stopped: Slow accrual

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01312818
Sponsor's protocol ID
2008LS113
Other IDs
MT2008-33R, 1010M91973, X05323
Status last verified
Dec 2017
First submitted
9 Mar 2011
Last updated
28 Dec 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bortezomib, Vorinostat and Dexamethasone in people with Acute Lymphoblastic Leukemia, run by Masonic Cancer Center, University of Minnesota 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 21 inclusion and 10 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 28 Dec 2017. 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 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 15 May 2015). 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?

Number of Subjects Who Achieved Complete Remission of Their Disease (time frame: Day 30). 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 NCT01312818.

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 28 Dec 2017.

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