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

Sponsor

Clavis Pharma (Industry)

Overall Status

Completed

CT.gov ID

NCT00405743

Collaborator

(none)

153

Enrollment

Locations

Arms

Duration (Months)

9.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies AML	Drug: CP-4055 Drug: CP-4055	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

153 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A CP4055, 2 and 4 hour 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

Arm

Intervention/Treatment

Experimental: Arm A

CP4055, 2 and 4 hour 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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Patients must be 18 years of age or older
Patients must have ECOG performance status (PS) of 0 - 2. See Appendix 3
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

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
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.
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

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

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
Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C
Pregnant and nursing patients are excluded
Uncontrolled intercurrent illness
Active heart disease
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
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:

Patients with hypersensitivity to idarubicin or any other component of the product, and/or other anthracyclines or anthracenediones

Contacts and Locations

Locations

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