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Chronic Lymphocytic LeukemiaPhase 2NCT00524667

HDAC Inhibitor Valproic Acid as an Effective Therapy for Chronic Lymphocytic Leukemia

A Phase 2 study testing Valproic acid & fludarabine in people with Chronic Lymphocytic Leukemia, run by CancerCare Manitoba at 1 site in Canada.

Terminated

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

Official record
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Trial summary

OBJECTIVES To investigate: the mechanism of Valproic Acid (VPA)-induced apoptosis in B-CLL the ability of VPA in combination with standard chemotherapy or new antitumor agents to induce a synergistic antitumor effect in chronic lymphocytic leukemia (CLL) cells the clinical efficacy of VPA in previously treated CLL… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Valproic acid & fludarabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteCanada
Study dates
Jan 2008to Jul 2011
Phase
Phase 2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Active CLL (as defined by the National Cancer Institute Working Group)
  • Patients must have received at least one prior therapy for CLL and have been treated with a nucleoside analogue.
  • Recruitment will be limited to those with an ECOG performance status of 2 or less.

Who cannot join

  • Patients who are pregnant or breastfeeding
  • Patients with a history of autoimmune cytopenias
  • Patients with platelets < 50 x 109/L or an absolute neutrophil count < 1.5X109/L
  • Patients with hepatic disease or an AST/ALT 6x above the upper limit of normal
  • Patients with a calculated creatinine clearance < 30 ml/min using the Cockroft and Gault formula
  • Patients with a history of pancreatitis
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  • Patients who are receiving drugs that affect VPA protein binding or metabolism
  • Patients with active infection, HIV or active viral hepatitis
  • Patients with active secondary malignancy or who have central nervous system involvement with CLL
  • Patients diagnosed with more an aggressive lymphoproliferative disorder such as Richter's transformation

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

OBJECTIVES

To investigate:

  • the mechanism of Valproic Acid (VPA)-induced apoptosis in B-CLL
  • the ability of VPA in combination with standard chemotherapy or new antitumor agents to induce a synergistic antitumor effect in chronic lymphocytic leukemia (CLL) cells
  • the clinical efficacy of VPA in previously treated CLL patients.

This will be an example of a translational research study where the results of our laboratory studies will be applied to a clinical trial in the CLL clinic at CancerCare Manitoba.

Read the detailed description

All participants will be treated with valproic acid (VPA) at a starting dose of 15 mg/kg/day orally in divided doses. This dose produces a VPA plasma level of 346-693 μM and is the recommended starting dose for patients with seizure disorder. Each week a pre-dose serum VPA level will be determined by immunoassay and the daily dose increased by 5 mg/kg/d to ensure a predose level > 1mM. Once the target dose has been achieved serum VPA levels will be determined on a monthly basis to ensure a pre dose level >1mM.

After completing 28 days of therapy participants will be examined and have lab work drawn (CBC with differential, electrolytes, BUN, creatinine, total protein, albumin, calcium, LDH, total and direct bilirubin, ALT/AST, and β2-microglobulin. Females of child bearing age will undergo a pregnancy test prior to each 28 day cycle). For participants identified as having stable or progressive disease (National Cancer Institute Criteria), Fludarabine (Flu) therapy will be added to VPA on a 28 day cycle. Oral Flu will be administered at a dose of 40 mg/m2/day on days 1-3 of a 28 day cycle in addition to VPA as described above. Dose adjustments for Flu will be based on creatinine clearance. All participants receiving fludarabine will receive irradiated blood products and pneumocystis carnii prophylaxis.

Treatment will be continued with VPA ± Flu to a maximum of six 28 day cycles. Therapy will be discontinued prior to six 28 day cycles if: a) the participant requests discontinuation, b) if the participant is unable to comply with the protocol, c) the medical care team thinks a change of therapy would be in the best interest of the participant, d) there is evidence of progressive disease after two cycles of VPA + Flu, e) if the participant experiences unacceptable toxicity attributable to the study drugs such as ≥3 non-hematological toxicity or prolonged grade 4 hematological toxicity (NCI common toxicity criteria, Table 5 of the protocol), f) if the AST/ALT increase to > 6x the upper limit of normal or g) the participant becomes pregnant.

Being tested
Valproic acid & fludarabine
Keywords
Active CLL
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • Valproic acid & fludarabineDrug

    valproic acid (VPA) starting dose of 15 mg/day p.o. in divided doses, increased weekly by 5 mg/kg/day until >1mM Fludarabine 40 mg/m2/day orally will be added after completing 28 days of VPA if participant has been identified as having stable or progressive disease.

Study groups in NCT00524667
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: Valproic acid & fludarabine

What is being measured

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

  1. Best clinical response as defined by NCIWG criteria for CLL

    Measured: 6 months after commencing therapy

Secondary outcomes (1)

  1. Effect of treatment on histone acetylation status; hematological toxicity (graded according to NCIWG criteria for CLL) and nonhematological toxicity (graded according to NCI common toxicity criteria)

    Measured: throughout therapy

Timeline

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

  1. First posted3 Sep 2007 (estimated)
  2. Study startJan 2008
  3. Primary completionJul 2011
  4. Study completionJul 2011

Why it stopped: Terminated due to poor 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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00524667
Sponsor's protocol ID
CCM-001
Status last verified
Jul 2011
First submitted
31 Aug 2007
Last updated
20 Jul 2011
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Valproic acid & fludarabine in people with Chronic Lymphocytic Leukemia, run by CancerCare Manitoba at 1 site in Canada.

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 3 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 20 Jul 2011. 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 Canada. 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?

The study was stopped early (reason given: Terminated due to poor accrual.). Results are not available in the source record.

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?

Best clinical response as defined by NCIWG criteria for CLL (time frame: 6 months after commencing therapy). 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 NCT00524667.

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 20 Jul 2011.

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