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LeukemiaPhase 2NCT00882206

Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia

A Phase 2 study testing cytarabine, decitabine and doxorubicin hydrochloride in people with Leukemia and Lymphoma, 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

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Decitabine and vorinostat may alter the cancer cells by reversing the cancer pathways needed for cell growth. Read more about this study

Who is it for?
Ages 2 to 60 years
Conditions the study is for
Leukemia, Lymphoma
What is being tested?
cytarabine, decitabine and doxorubicin hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Apr 2009to 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 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis of lymphoblastic lymphoma or acute lymphoblastic leukemia with ≥ 5% blasts in the bone marrow (M2/M3) (with or without extramedullary disease) that meets 1 of the following criteria:
  • Refractory disease/induction failure (failure to achieve initial remission after 2 lines of induction therapy)
  • Relapsed disease (in first relapse or higher)
  • Central nervous system (CNS)-positive disease allowed
  • Karnofsky performance status (PS) 50-100% (for patients ≥ 16 years of age) OR Lansky PS 50-100% (for patients < 16 years of age)
  • Life expectancy ≥ 8 weeks
Show all 32Show fewer
  • Creatinine clearance ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
  • 0.4 mg/dL (for patients 1 to 5 months of age)
  • 0.5 mg/dL (for patients 6 to 11 months of age)
  • 0.6 mg/dL (for patients 1 year of age)
  • 0.8 mg/dL (for patients 2 to 5 years of age)
  • 1.0 mg/dL (for patients 6 to 9 years of age)
  • 1.2 mg/dL (for patients 10 to 12 years of age)
  • 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
  • 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
  • ALT < 5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN for age
  • LVEF ≥ 40% by ECHO/MUGA scan
  • Shortening fraction > 29% by ECHO/MUGA scan
  • Able to swallow capsules
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after completion of study treatment
  • No untreated positive blood cultures or progressive infections as assessed by radiographic studies
  • No known allergy to any of the agents or their ingredients used in this study
  • Patients with clinically significant prior allergies to pegaspargase may be treated with asparaginase-Erwinia, if available
  • Patients who cannot receive asparaginase on this study (e.g., due to prior pancreatitis, stroke, or other toxicity) are eligible provided they meet all other inclusion/exclusion criteria
  • Recovered from prior therapy (defined as CTCAE v3.0 toxicity ≤ grade 1)
  • More than 3 weeks since prior chemotherapy for cancer other than hydroxyurea for patients with WBC > 10,000/mm³
  • At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)
  • At least 1 month since prior biologic therapy, such as monoclonal antibodies
  • At least 3 months since prior hematopoietic stem cell transplantation

Who cannot join

  • Evidence of graft-versus-host disease
  • Concurrent valproic acid
  • Concurrent coumadin/warfarin other than a short course administered in a prophylactic setting

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Minnesota Amplatz Children's Hospital

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: A Therapeutic Trial of Decitabine and Vorinostat in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Decitabine and vorinostat may alter the cancer cells by reversing the cancer pathways needed for cell growth. Giving more than one drug (combination chemotherapy) together with decitabine and vorinostat may kill more cancer cells than with chemotherapy alone.

PURPOSE: This phase II trial is studying how well giving decitabine and vorinostat together with combination chemotherapy works in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma that has relapsed or not responded to treatment.

Read the detailed description

OBJECTIVES:

Primary

  • Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies. Samples are analyzed for hypermethylation at diagnosis and demethylation post-exposure with decitabine and vorinostat using LINE methylation.

OUTLINE:

Patients receive decitabine IV over 1 hour and oral vorinostat twice daily on days 1-4; vincristine sulfate IV on days 5, 12, 19, and 26; oral prednisone twice daily on days 5-33; doxorubicin hydrochloride IV over 15 minutes and cytarabine intrathecally (IT) on day 5; pegaspargase IV or intramuscularly on days 6, 12, 19, and 26; and methotrexate* IT on days 12 and 33. Patients with Philadelphia chromosome-positive disease may also receive oral imatinib mesylate once daily on days 5-33.

NOTE: *Patients with central nervous system (CNS)-positive disease also receive methotrexate IT on days 19 and 26.

Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies.

After completion of study treatment, patients are followed for 60 days.

Conditions
Leukemia, Lymphoma
Keywords
recurrent adult lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia
Medical subject headings
Leukemia, Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • cytarabineDrug

    Also called cytosine arabinoside

    At baseline when peripheral blood draw and bone marrow aspirate performed.

    *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.

  • decitabineDrug

    Also called Dacogen(R)

    Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour

  • doxorubicin hydrochlorideDrug

    Also called Doxorubicin

    Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes

  • imatinib mesylateDrug

    Also called Gleevec(R)

    340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33.

  • methotrexateDrug

    Also called MTX

    **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.

  • pegaspargaseDrug

    Also called PEG asparaginase

    2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)

  • prednisoneDrug

    40mg/m2/day divided BID (days 5 - 33)

  • vincristine sulfateDrug

    Also called Oncovin(R)

    1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26)

  • vorinostatDrug

    Also called suberoylanilide hydroxamic acid (SAHA)

    Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily)

Study groups in NCT00882206
Study groupRoleWhat they receive
Decitabine / VorinostatExperimentalThis is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
Receives: Drug: cytarabine; Drug: decitabine; Drug: doxorubicin hydrochloride; Drug: imatinib mesylate; Drug: methotrexate; Drug: pegaspargase; Drug: prednisone; Drug: vincristine sulfate; Drug: vorinostat

What is being measured

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

  1. Response to Treatment

    Response includes both complete remission (defined as <5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)

    Measured: Day 33

Secondary outcomes (3)

  1. Level of Methylation

    the percentage of methylated DNA

    Measured: Day 0

  2. Level of Methylation

    the percentage of methylated DNA

    Measured: Day 5

  3. Level of Methylation

    the percentage of methylated DNA

    Measured: Day 33

Timeline

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

  1. First posted16 Apr 2009 (estimated)
  2. Study startApr 2009
  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
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00882206
Sponsor's protocol ID
2008LS112
Other IDs
0810M50401, MT2008-29R
Status last verified
Dec 2017
First submitted
15 Apr 2009
Last updated
28 Dec 2017
Data monitoring committee
Yes

Publications

  • Burke MJ, Lamba JK, Pounds S, Cao X, Ghodke-Puranik Y, Lindgren BR, Weigel BJ, Verneris MR, Miller JS. A therapeutic trial of decitabine and vorinostat in combination with chemotherapy for relapsed/refractory acute lymphoblastic leukemia. Am J Hematol. 2014 Sep;89(9):889-95. doi: 10.1002/ajh.23778. Epub 2014 Jun 27.

    PubMed 24891274

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cytarabine, decitabine and doxorubicin hydrochloride in people with Leukemia and Lymphoma, 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 32 inclusion and 3 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 28 Oct 2016). 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?

Response to Treatment (time frame: Day 33). 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 NCT00882206, 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 28 Dec 2017.

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