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

NCT00780143 | Terminated Phase 1 Results

• 1 other identifier: APL-A-007-06
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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 relapsed/refractory AML treated at the MTD.

Conditions

Relapsed/Refractory Leukemia

Keywords

Tumor; Leukemia; Plitidepsin; Aplidin

Outcome Measures

Primary Outcomes (3)

• 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.

  Until disease progression or unacceptable toxicity

• 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.

  Until disease progression or unacceptable toxicity

• Response Rate

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

  Until disease progression or unacceptable toxicity

Study Arms (1)

Arm 1

EXPERIMENTAL

Plitidepsin in combination with Cytarabine

Drug: Plitidepsin plus Cytarabine

Interventions

Plitidepsin plus Cytarabine DRUG

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.

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (1)

The Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

MeSH Terms

Conditions

Leukemia; Neoplasms

Interventions

plitidepsin; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Clinical Development Department of PharmaMar´s Oncology,Business Unit.,
• Organization: Pharma Mar, S.A.

clinicaltrials@pharmamar.com

+34 918466000

Study Officials

• Mecide Gharibo, M.D.

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2008
• First Posted: October 27, 2008
• Study Start: November 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: November 9, 2018
• Results First Posted: November 9, 2018

Record last verified: 2013-11

Locations

US (1)