A Phase I/II Study of CP-4055 in Patients With Refractory/Relapsed Hematologic Malignancies

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

Study Overview

• Status: Completed
• Conditions: AML; Hematologic Malignancies
• Intervention / Treatment: Drug: CP-4055; Drug: CP-4055

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.

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69437
    • Centre Hospitalier Universitaire, CHU de Lyon, Service d'Hematologie Clinique
  • Marseille, France, 13273
    • Institut Paoli-Calmettes
  • Toulouse, France, 40031-31059
    • Centre Hospitalier Universitaire CHU de Toulouse, Hopital Purpan
  • Paris
    • Bobigny, Paris, France, 93009
      • Hematology Service, Hôpital Beaujon and Hôpital Avicenne
• Germany
  • Berlin, Germany, 12200
    • University Hospital Benjamin Franklin Med.Clinic III
  • Frankfurt am Main, Germany, 60590
    • Department of Internal Medicine Klinikum der Johann Wolfgang Goethe-Universität Medizinische Klinik II
  • Münster, Germany, 48129
    • Westfälische Wilhelms-Universität Münster Medizinische Klinik und Polikinik Innere Medizin A
• Italy
  • Bologna, Italy, 40138
    • Institute of Hematology & Medical Oncology L and A Serágnoli University of Bologna
  • Rome, Italy, 00133
    • Universitá degli Studi di Roma Ematologia- Policlinico Tor Vergata
• Norway
  • Oslo, Norway, 0407
    • Department of Hematology, Ullevål University Hospital, University of Oslo
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
• United States
  • New York
    • Valhalla, New York, United States, 10595
      • Mew York Medical College, Division of Oncology
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center (DUMC)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Institute for Drug Development (IDD), Cancer Therapy and Research Center, 7979 Wurzbach Rd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; CP4055, 2 and 4 hour IV infusion	Drug: CP-4055; CP-4055 Continuous IV infusion; Drug: CP-4055; CP4055 2 and 4 hour IV infusion
Experimental: Arm B; CP-4055, Continuous IV infusion	Drug: CP-4055; CP-4055 Continuous IV infusion; Drug: CP-4055; CP4055 2 and 4 hour IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase I: Determine the MTD and PK properties of CP-4055 single agent.	Q4 2007
Phase II: Determine the efficacy of CP-4055 single agent in AML	Q4 2007

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase I: Evaluate the safety profile of CP-4055 single agent.	Q4 2007
Determine the MTD and PK of CP-4055 in combination with idarubicin.	Q2 2008
Phase II: Extended evaluation of the safety profile of CP-4055 single agent in AML	Q2 2008

Collaborators and Investigators

• Sponsor: Clavis Pharma
• Investigators: Principal Investigator: Francis J Giles, MD, Institute for Drug Development (IDD), Cancer Therapy and Research Center, San Antonio, Texas, USA

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: November 29, 2006
• First Submitted That Met QC Criteria: November 29, 2006
• First Posted (Estimate): November 30, 2006

Study Record Updates

• Last Update Posted (Estimate): September 18, 2013
• Last Update Submitted That Met QC Criteria: September 12, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Cancer; Relapsed; Refractory; AML; ALL; Leukemia; MDS; CLL; CML; Hematologic Malignancies; CMML; CP-4055; ELACYT™; AMM
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: CP4055-106