Clinical trial NCT00405743: A Phase I/II Study of CP-4055 in Patients With Refractory/Relapsed Hematologic Malignancies
Official title: A Phase I/II Study of CP-4055 in Patients With Refractory/Relapsed Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematologic Malignancies
AML
Keywords: CP-4055
ELACYT™
Cancer
Refractory
Relapsed
Hematologic Malignancies
Leukemia
ALL
AML
AMM
CLL
CML
CMML
MDS
Lead sponsor: Clavis Pharma
Sponsor class: INDUSTRY
First posted: 2006-11-30
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with refractory or relapsed hematologic malignancies will receive CP-4055 intravenously(IV) on Day 1-5 every three weeks until complete response or disease worsening/progressing

Detailed description: This is a multicentre clinical study conducted in the USA and in Europe. It is an open label, dose escalation study designed to characterize the safety, tolerability, pharmacokinetics (PK), and efficacy of CP-4055 as a single agent when administered as a 2 hours intravenous (IV) or a continuous IV (CIV) infusion administered daily for 5 days in a 21-day cycle, either alone or with idarubicin IV, in patients with refractory/relapsed hematologic malignancies who have either failed potentially curative therapy or are considered unsuitable for standard therapy.

In a second phase of the study the efficacy of single agent CP-4055 in patients with AML may be assessed.

It is intended that patients receive a minimum of two cycles of therapy in the absence of unacceptable toxicity or significant disease progression.

Eligibility criteria: Inclusion Criteria:

ARM A and B: Phase I CP-4055 single agent 1. Patients must have relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable response or have failed potentially curative therapy, or have refused or are considered unsuitable for standard therapy

ARM C: CP-4055 in combination with idarubicin

1. Patients with relapsed/refractory AML for which no standard therapies are anticipated to result in a durable response or who have failed potentially curative therapy, or who refuse or are considered unsuitable for standard therapy

   ARM A, B, C: CP-4055 as single agent and/or in combination with idarubicin
2. Patients must be 18 years of age or older
3. Patients must have ECOG performance status (PS) of 0 - 2. See Appendix 3
4. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study. Nursing patients are excluded.

   Male and female patients must use acceptable contraceptive methods for the duration of time on study, and males also for 3 months after the last CP-4055 dose
5. Patients must be capable of understanding and complying with parameters as outlined in the protocol, and able and willing to sign a written informed consent form
6. In the absence of rapidly progressing disease, the interval from prior treatment to time of study drug administration should be at least 2 weeks for cytotoxic agents, or at least 5 half-lives for noncytotoxic agents.
7. Patients must have the following clinical laboratory values:

   * Serum creatinine less or equal to 1.5 x the institutional upper limit of normal (ULN)
   * Total bilirubin less or equal to 1.5 x the ULN unless considered due to Gilbert's syndrome
   * Alanine aminotransferase (ALT) (SGPT), or aspartate aminotransferase (AST) (SGOT) less or equal to 2.5 x the ULN unless considered due to organ leukemic involvement

Phase II

1. Patients with a confirmed diagnosis of AML who have received cytotoxic chemotherapy

2 - 7. Identical to inclusion criteria nos. 2 - 7 for phase I

Exclusion Criteria:

Phase I AND II

1. A history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to CP-4055, i.e., ara-C and/or egg
2. Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C
3. Pregnant and nursing patients are excluded
4. Uncontrolled intercurrent illness
5. Active heart disease
6. Patients receiving any other standard or investigational cytotoxic treatment for their hematologic malignancy other than a maximum of 5 g of hydroxyurea to a maximum of 5 days in cycle 1 of therapy
7. Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities

   Exclusion criteria no. 8 applies only in arm C:
8. Patients with hypersensitivity to idarubicin or any other component of the product, and/or other anthracyclines or anthracenediones

Primary outcomes:
measure: Phase I: Determine the MTD and PK properties of CP-4055 single agent.
timeFrame: Q4 2007
measure: Phase II: Determine the efficacy of CP-4055 single agent in AML
timeFrame: Q4 2007
Secondary outcomes:
measure: Phase I: Evaluate the safety profile of CP-4055 single agent.
timeFrame: Q4 2007
measure: Determine the MTD and PK of CP-4055 in combination with idarubicin.
timeFrame: Q2 2008
measure: Phase II: Extended evaluation of the safety profile of CP-4055 single agent in AML
timeFrame: Q2 2008
Other outcomes:
Locations:
city: Valhalla
country: United States
facility: Mew York Medical College, Division of Oncology
state: New York
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Institute for Drug Development (IDD), Cancer Therapy and Research Center, 7979 Wurzbach Rd.
state: Texas
city: Bobigny
country: France
facility: Hematology Service, Hôpital Beaujon and Hôpital Avicenne
state: Paris
city: Lyon
country: France
facility: Centre Hospitalier Universitaire, CHU de Lyon, Service d'Hematologie Clinique
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire CHU de Toulouse, Hopital Purpan
city: Berlin
country: Germany
facility: University Hospital Benjamin Franklin Med.Clinic III
city: Frankfurt am Main
country: Germany
facility: Department of Internal Medicine Klinikum der Johann Wolfgang Goethe-Universität Medizinische Klinik II
city: Münster
country: Germany
facility: Westfälische Wilhelms-Universität Münster Medizinische Klinik und Polikinik Innere Medizin A
city: Bologna
country: Italy
facility: Institute of Hematology & Medical Oncology L and A Serágnoli University of Bologna
city: Rome
country: Italy
facility: Universitá degli Studi di Roma Ematologia- Policlinico Tor Vergata
city: Oslo
country: Norway
facility: Department of Hematology, Ullevål University Hospital, University of Oslo
city: Manchester
country: United Kingdom
facility: Christie Hospital
Study officials:
affiliation: Institute for Drug Development (IDD), Cancer Therapy and Research Center, San Antonio, Texas, USA
name: Francis J Giles, MD
role: PRINCIPAL_INVESTIGATOR
References: