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

Phase 1

Completed

• Conditions: Hematologic Malignancies; AML
• Interventions: Drug: CP-4055

• Registration Number: NCT00405743
• Lead Sponsor: Clavis Pharma

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.

Study Timeline

• Study Start: 2006-05
• Study First Submitted: 2006-11-29
• Study First Submitted QC: 2006-11-29
• Study First Posted: 2006-11-30
• Primary Completion: 2009-05
• Study Completion: 2010-05
• Status Verified: 2013-09
• Disposition First Submitted: 2013-09-12
• Disposition First Submitted QC: 2013-09-12
• Last Update Submitted: 2013-09-12
• Disposition First Posted: 2013-09-18
• Last Update Posted: 2013-09-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 153

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	CP-4055	CP-4055, Continuous IV infusion
Arm A	CP-4055	CP4055, 2 and 4 hour IV infusion

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (16)

Mew York Medical College, Division of Oncology; 🇺🇸 Valhalla, New York, United States

Duke University Medical Center (DUMC); 🇺🇸 Durham, North Carolina, United States

Institute for Drug Development (IDD), Cancer Therapy and Research Center, 7979 Wurzbach Rd.; 🇺🇸 San Antonio, Texas, United States

Hematology Service, Hôpital Beaujon and Hôpital Avicenne; 🇫🇷 Bobigny, Paris, France

Department of Hematology, Ullevål University Hospital, University of Oslo; 🇳🇴 Oslo, Norway

Centre Hospitalier Universitaire CHU de Toulouse, Hopital Purpan; 🇫🇷 Toulouse, France

Centre Hospitalier Universitaire, CHU de Lyon, Service d'Hematologie Clinique; 🇫🇷 Lyon, France

Christie Hospital; 🇬🇧 Manchester, United Kingdom

University Hospital Benjamin Franklin Med.Clinic III; 🇩🇪 Berlin, Germany

Cleveland Clinic Taussig Cancer Center; 🇺🇸 Cleveland, Ohio, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

Department of Internal Medicine Klinikum der Johann Wolfgang Goethe-Universität Medizinische Klinik II; 🇩🇪 Frankfurt am Main, Germany

Institute of Hematology & Medical Oncology L and A Serágnoli University of Bologna; 🇮🇹 Bologna, Italy

Westfälische Wilhelms-Universität Münster Medizinische Klinik und Polikinik Innere Medizin A; 🇩🇪 Münster, Germany

Universitá degli Studi di Roma Ematologia- Policlinico Tor Vergata; 🇮🇹 Rome, Italy