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Relapsed/Refractory LeukemiaPhase 1/2NCT00780143

Clinical Study of Plitidepsin (Aplidin®) in Combination With Cytarabine in Patients With Relapsed/Refractory Leukemia

A Phase 1/2 study testing Plitidepsin plus Cytarabine in people with Relapsed/Refractory Leukemia, run by PharmaMar 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

This is a Phase I/II study to determine the safety, tolerability and to identify the MTD and DLT of Plitidepsin in combination with a fixed dose of Cytarabine in patients with relapsed/refractory leukemia and to determine the response rate of the combination of Plitidepsin with Cytarabine in patients with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed/Refractory Leukemia
What is being tested?
Plitidepsin plus Cytarabine
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
Nov 2007to Jun 2009
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have cytologically (or by flow cytometry) documented relapsed/refractory Acute Myeloid leukemia or Acute Lymphoid leukemia for which no standard therapy is anticipated to result in a durable remission. Chronic Myeloid leukemia in blast crisis who progress through Gleevec® or is intolerant to Gleevec® or other FDA approved BCR-ABL Tyrosine Kinase Inhibitors. Patients with untreated AML or ALL who are electing not to receive standard therapy are also eligible. Relapsed/refractory leukemia patients may combination after 1 course of chemotherapy. In addition,leukemia secondary to pre-existing hematologic disorders high-grade myelodysplastic syndromes are also eligible.
  • ≥18 years of age.
  • Patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines.
  • Patients who cannot provide informed consent will not be eligible for the study.
  • Prior radiotherapy, chemotherapy or biologic therapies are allowed. Previous line(s) of systemic chemotherapy should have been completed at least 2 weeks prior to starting protocol treatment. Concurrent hydroxyurea administration will be allowed to control WBC count, platelet count, or symptoms and will be discontinued 24 hours prior to the first APLIDIN® dose. For patients with CML in blast crisis, Gleevec® or other BCR-ABL Tyrosine Kinase Inhibitors must be stopped at least 7 days prior to the first APLIDIN® dose. t.
  • Patients must have an ECOG performance status ≤2 (Appendix C).
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  • Laboratory data:
  • Serum Total Bilirubin < 1.5 mg/dL X institutional ULN (except when Gilbert syndrome is clearly documented and other LFTs are normal).
  • AST (SGOT)/ALT (SGPT)/ALKP ≤ 2.5 X institutional ULN.
  • Creatinine clearance > 40 ml/min, calculated according to Cockcroft and Gault's formula (Appendix D).
  • Negative pregnancy test for women of childbearing potential.
  • Bone Marrow Assessment within two weeks before the first Aplidin® administration.
  • Estimated life expectancy of > 1 month.
  • Left ventricular ejection fraction within normal limits.

Who cannot join

  • Previous treatment with Plitidepsin.
  • Prior autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT) patients are not eligible due to higher risk of toxicity related to treatment after such procedure.
  • Active or metastatic secondary primary malignancy.
  • Patients with known Central Nervous System involvement will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Serious concomitant systemic disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, including the following specific conditions:
  • Uncontrolled psychiatric illness or medical illness that the principle investigator feels will compromise the patient's tolerance of the study medication.
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  • Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
  • Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
  • Uncontrolled systemic infection.
  • Other relevant cardiac conditions:
  • History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure.
  • Previous mediastinal radiotherapy.
  • Uncontrolled arterial hypertension despite optimal medical therapy.
  • Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m².
  • Any grade of cardiac arrhythmia according to CTCAE v3.0 (see appendix F) with exception of < grade 3 supraventricular tachycardia proven to be in response to medical conditions as anemia, fever, etc. from his/her underlying leukemia.
  • History of hypersensitivity reaction to cremophor, Cytarabine, Mannitol, or Plitidepsin (Aplidin®).
  • Myopathy or any clinical situation that causes significant and persistent elevation of CK (> 2.5 ULN in two different determinations performed with one week apart).
  • History of significant Cytarabine related neurotoxicity.
  • Grade >2 motor or sensory neuropathy of any cause.
  • Men and women of reproductive potential who are not using effective contraceptive methods. The effects of Plitidepsin on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 6 months after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Also, if the wife or female partner of a male patient becomes pregnant during the study, the investigator must be notified promptly and the pregnant woman will be referred for appropriate follow-up with a High-risk Obstetrician.
  • Pregnant and/or lactating women.
  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, therefore, known HIV-positive patients with active HIV infection and/or receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Plitidepsin or other agents administered during the study. HIV testing is not required unless infection is clinically suspected.
  • Known active HBV or HCV infection. Patients with any serological evidence of current or past hepatitis B exposure are excluded unless the serological findings are clearly due to vaccination. HBV or HCV testing are not required unless infection is clinically suspected.
  • Concomitant therapy with therapeutic dose of coumadin is not permitted. A suboptimal dose for permeability venous access devices is allowed.
  • Treatment with any investigational product in the 30 days period before inclusion in the study. Wash-out periods since the end of the precedent therapy less than:
  • 6 weeks for nitrosoureas or high dose chemotherapy.
  • 2 weeks for other chemotherapies or biological agents.
  • 4 weeks for radiation or radionuclide therapy (6 weeks in case of prior extensive external beam radiation, more than 25% of bone marrow distribution).
  • 24 hours for hydroxyurea.
  • 7 days for Gleevec® or other BCL-ABL tyrosine Kinase inhibitors.
  • Limitation of the patient´s ability to comply with the treatment or follow-up protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

Other trials in United States

About this study

Official title: Phase I/II Study of Plitidepsin (Aplidin®) in Combination With Cytarabine in Patients With Relapsed/Refractory Leukemia

This is a Phase I/II study to determine the safety, tolerability and to identify the MTD and DLT of Plitidepsin in combination with a fixed dose of Cytarabine in patients with relapsed/refractory leukemia and to determine the response rate of the combination of Plitidepsin with Cytarabine in patients with relapsed/refractory AML treated at the MTD.

Read the detailed description

This is a Phase I/II study to determine:

  • the safety, tolerability and to identify the MTD and DLT of Plitidepsin in combination with a fixed dose of Cytarabine in patients with relapsed/refractory leukemia and to determine the response rate of the combination of Plitidepsin with Cytarabine in patients with relapsed/refractory AML treated at the MTD.
  • the pharmacokinetic parameters of Plitidepsin in combination with Cytarabine.
  • whether Plitidepsin in combination with Cytarabine exerts antiangiogenic effects as measured by reduction in microvessel density and VEGFR-1 expression in bone marrow biopsies of patients with relapsed/refractory leukemia.
  • whether measurement of free serum VEGF levels, soluble circulating VEGF Receptor and Peripheral Progenitor Endothelial cells provide an early marker of response to Plitidepsin.
  • the effects of Plitidepsin and Cytarabine on cytidine deaminase activity and correlate results with Cytarabine drug resistance.
  • changes in leukemic gene expression as a result of Plitidepsin and Cytarabine administration.
  • tumor response duration.
  • progression free survival and overall survival.
Being tested
Plitidepsin plus Cytarabine
Keywords
Tumor, Leukemia, Plitidepsin, Aplidin
Medical subject headings
Leukemia, Neoplasms

What participants receive

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

  • Plitidepsin plus CytarabineDrug

    Plitidepsin 0.54 mg /m2 (initial dose)daily x 5 one hour infusion every 3 weeks plus Cytarabine 1 g/m2 daily for 5 days.

Study groups in NCT00780143
Study groupRoleWhat they receive
Arm 1ExperimentalPlitidepsin in combination with Cytarabine
Receives: Drug: Plitidepsin plus Cytarabine

What is being measured

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

  1. Máximum Tolerate Dose

    To determine the maximum tolerated dose (MTD) of Plitidepsin (Aplidin®) when administered daily x 5 days with a fixed dose of Cytarabine for 5 days every four weeks in patients with relapsed/refractory leukemia.

    Measured: Until disease progression or unacceptable toxicity

  2. Dose Limiting Toxicity

    To determine the dose limiting toxicity (DLT) of Plitidepsin (Aplidin®) when administered daily x 5 days with a fixed dose of Cytarabine for 5 days every four weeks in patients with relapsed/refractory leukemia.

    Measured: Until disease progression or unacceptable toxicity

  3. Response Rate

    To determine the response rate of the combination of Plitidepsin with Cytarabine in patients with relapsed/refractory AML treated at the MTD.

    Measured: Until disease progression or unacceptable toxicity

Timeline

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

  1. First posted27 Oct 2008 (estimated)
  2. Study startNov 2007
  3. Primary completionJun 2009
  4. Study completionJun 2009

Why it stopped: Poor recruitment

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 1/2
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
NCT00780143
Sponsor's protocol ID
APL-A-007-06
Status last verified
Nov 2013
First submitted
24 Oct 2008
Last updated
9 Nov 2018
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Plitidepsin plus Cytarabine in people with Relapsed/Refractory Leukemia, run by PharmaMar 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 14 inclusion and 31 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 9 Nov 2018. 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 combined 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.

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 9 Nov 2018). 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?

Máximum Tolerate Dose (time frame: Until disease progression or unacceptable toxicity). 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 NCT00780143.

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 9 Nov 2018.

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