Alvocidib in Patients With Previously Treated Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia Arising From Chronic Lymphocytic Leukemia (CLL)

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT00464633

Collaborator

(none)

165

Enrollment

Locations

Arm

Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Multicenter, open-label, study of alvocidib in previously treated chronic lymphocytic leukemia patients.

Primary objective is to determine overall response rate.

The secondary objectives are:

to assess overall safety,
to assess duration of response, progression free survival, and overall survival.

Clinical benefit and pharmacokinetics parameters are also evaluated.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Chronic	Drug: alvocidib	Phase 2

Detailed Description

Treatment until disease progression or no evidence of treatment response; occurrence of unacceptable toxicity, intercurrent medical problem, or adverse event (AE); or a maximum of 6 cycles.

Follow-up of 6 months after the last treatment with alvocidib.

The maximum duration of the study participation for patient will be about 15 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

165 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Open-label, Single Arm Study of Weekly Alvocidib in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL) or Prolymphocytic Leukemia (PLL) Arising From CLL

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alvocidib Cycles with 4-week treatment with alvocidib followed by 2-week rest period for up to a maximum of 6 cycles	Drug: alvocidib 1st dose: 30 mg/m2 as a 30-minute intravenous (IV) infusion followed by 30 mg/m2 as a 4-hour continuous infusion Then, every treatment week, depending upon the patient's objective response to initial therapy: 30 mg/m2 over 30 minutes followed by 50 mg/m2 over 4 hours or 30 mg/m2 over 30 minutes followed by 30 mg/m2 over 4 hours. Other Names: HMR1275

Arm

Intervention/Treatment

Experimental: Alvocidib

Cycles with 4-week treatment with alvocidib followed by 2-week rest period for up to a maximum of 6 cycles

Drug: alvocidib

1st dose: 30 mg/m2 as a 30-minute intravenous (IV) infusion followed by 30 mg/m2 as a 4-hour continuous infusion Then, every treatment week, depending upon the patient's objective response to initial therapy: 30 mg/m2 over 30 minutes followed by 50 mg/m2 over 4 hours or 30 mg/m2 over 30 minutes followed by 30 mg/m2 over 4 hours.

Other Names:

HMR1275

Outcome Measures

Primary Outcome Measures

Best overall objective response rate [Up to a maximum of 6 cycles]
Objective Response Rate (ORR) is defined as the proportion of participants with complete response or partial response (including nodular partial response) relative to the total number of participants. Response assessment is based on evaluation of nodal disease by Computerized Tomography (CT) and National Cancer Institute Working Group 96 criteria (NCI-96) for assessment of liver, spleen, constitutional symptoms, peripheral blood (±) bone marrow.

Secondary Outcome Measures

Progression-free survival [Up to a maximum of 6 cycles]
Progression-free survival (PFS) is defined as the time from the date of first administration of study drug to the first documentation of progressive disease or death due to any cause in the absence of previous documentation of objective progression.
Duration of objective response [Up to a maximum of 6 cycles]
Duration of objective response is defined from the time of first occurrence of complete response or partial response (including nodular partial response) to the first documentation of progressive disease or death due to any cause in the absence of previous documentation of objective progression.
Overall survival [Up to a maximum of 6 cycles]
Overall survival (OS) is defined as the time from the date of first administration of study drug to death.
Overview of adverse events [from study drug administration up to 30 days after last study drug administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must have documentation of histologically confirmed and measurable Chronic Lymphocytic Leukemia (CLL) or Prolymphocytic Leukemia (PLL) arising from CLL;
Patient must have symptomatic and progressive disease;
Patient must have received prior alkylating agent(s) and be fludarabine refractory;
Patient must have the adequate organ functions;
Patient's Eastern Cooperative Oncology Group performance (ECOG) status must be 0-2;

Exclusion Criteria:

Patient with de novo PLL;
Patient with secondary malignancy that will limit survival ≤5 years;
Patient with prior allogenic or autologous bone marrow transplant or peripheral blood stem cell transplant ≤12 months;
Patient receiving an investigational agent or an approved agent for an investigational purpose within last 4 weeks prior to study entry;
Patient with known history of glucose-6-phosphate dehydrogenase deficiency;
Patient with autoimmune hemolytic anemia;
Patient with known Central Nervous System involvement;
Patient with active, uncontrolled serious bacterial, viral or fungal infections

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi-Aventis Investigational Site Number 840008	San Diego	California	United States	92103
2	Sanofi-Aventis Investigational Site Number 840022	San Francisco	California	United States	94143
3	Sanofi-Aventis Investigational Site Number 840010	Chicago	Illinois	United States	60611
4	Sanofi-Aventis Investigational Site Number 840012	Chicago	Illinois	United States	60637
5	Sanofi-Aventis Investigational Site Number 840017	Indianapolis	Indiana	United States	46202
6	Sanofi-Aventis Investigational Site Number 840001	Boston	Massachusetts	United States	02115
7	Sanofi-Aventis Investigational Site Number 840023	Ann Arbor	Michigan	United States	48109-0759
8	Sanofi-Aventis Investigational Site Number 840005	New York	New York	United States	10021
9	Sanofi-Aventis Investigational Site Number 840006	New York	New York	United States	10029-6574
10	Sanofi-Aventis Investigational Site Number 840003	Durham	North Carolina	United States	27710
11	Sanofi-Aventis Investigational Site Number 840018	Cleveland	Ohio	United States	44106
12	Sanofi-Aventis Investigational Site Number 840002	Columbus	Ohio	United States	43210
13	Sanofi-Aventis Investigational Site Number 840020	Philadelphia	Pennsylvania	United States	19104
14	Sanofi-Aventis Investigational Site Number 036001	St Leonards		Australia	2065
15	Sanofi-Aventis Investigational Site Number 056006	Brugge		Belgium	8000
16	Sanofi-Aventis Investigational Site Number 056001	Bruxelles		Belgium	1000
17	Sanofi-Aventis Investigational Site Number 056004	Gent		Belgium	9000
18	Sanofi-Aventis Investigational Site Number 056003	Leuven		Belgium	3000
19	Sanofi-Aventis Investigational Site Number 056002	Yvoir		Belgium	5530
20	Sanofi-Aventis Investigational Site Number 250001	Paris Cedex 13		France	75651
21	Sanofi-Aventis Investigational Site Number 250003	Pierre Benite Cedex		France	69495
22	Sanofi-Aventis Investigational Site Number 250002	Tours		France	37044
23	Sanofi-Aventis Investigational Site Number 276004	Kiel		Germany	24116
24	Sanofi-Aventis Investigational Site Number 276001	Köln		Germany	50937
25	Sanofi-Aventis Investigational Site Number 276002	Ulm		Germany	89081
26	Sanofi-Aventis Investigational Site Number 380002	Bologna		Italy	40138
27	Sanofi-Aventis Investigational Site Number 380001	Milano		Italy	20132
28	Sanofi-Aventis Investigational Site Number 528003	Amsterdam		Netherlands	1081 HV
29	Sanofi-Aventis Investigational Site Number 528001	Groningen		Netherlands	9713 GZ
30	Sanofi-Aventis Investigational Site Number 528002	Rotterdam		Netherlands	3015 CE
31	Sanofi-Aventis Investigational Site Number 630001	San Juan		Puerto Rico	00927
32	Sanofi-Aventis Investigational Site Number 826005	Aberdeen		United Kingdom	AB25 2ZN
33	Sanofi-Aventis Investigational Site Number 826002	Birmingham		United Kingdom	B9 5SS
34	Sanofi-Aventis Investigational Site Number 826004	Bournemouth		United Kingdom	BH7 7DW