Back to results

Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Acute Myeloid Leukemia (HEMOS AML 0106)

Primary Purpose

Acute Myeloid Leukemia

Status

Unknown status

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Tipifarnib plus Bortezomib

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute myeloid leukemia, NFkB activity and leukemia, expression of NFkB

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Provision of written informed consent
Male or female aged >18 years with newly diagnosed Acute Myeloid Leukemia (AML), de novo or secondary, unfit for conventional chemotherapy
Male or female with Acute Myeloid Leukemia in first relapse ( > 60 years)
WHO performance status ³ 2, or/and unwillingness to receive conventional chemotherapy
Negative pregnancy test or evidence of post-menopausal status for female patients.
RASGRP1/APTX gene expression ratio calculated at the screening >10 (part B.2 only)

Exclusion Criteria:

Serum bilirubin 2 x> Upper Limit of Normal (ULN)
Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.5 x ULN
Serum creatinine ³ 2.5 x ULN or 24-hour creatinine clearance £ 60 mL/min (measured or calculated by Cockcroft-Gault)
Patients with AML of FAB M3 classification (APL)
Patients with a history of another primary malignancy within the previous 1 year other than basal cell carcinoma or carcinoma in situ, the patient is in remission
Any clinically defined central nervous system AML.
Participation in an investigational drug study within the 30 days prior to entry
Evidence of uncontrolled infection or CNS-Hemorrhagic
Patients with documented cases of human immunodeficiency virus (HIV)
Peripheral Neuropathy or Neuropathic Pain grade > or = 2
Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 7,NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
RASGRP1/APTX gene expression ratio calculated at the screening <10 (part B.2 only)

Sites / Locations

Istituto di Ematologia "L e A Seragnoli" Policlinico S.Orsola-MalpighiRecruiting

Outcomes

Primary Outcome Measures

PART A: Assess the safety and tolerability of combined use of Zarnestra plus multiple ascending doses of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in first or subsequent relapse ( >60 years).(COMPLETED)

Part B.1: Assess the effect of Tipifarnib plus the defined in part A dose of Velcade in patients with de novo AML unfit for conventional chemotherapy (age >18 years) or in Patients in first or subsequent relapse ( >60 years) (COMPLETED)

Part B.2: Evaluate the overall response (CR, PR, HI) of patients with a RASGRP1/APTX gene expression ratio > 10, identified as predictive of a good clinical response to tipifarnib in patients with de novo AML unfit for conventional chemotherapy.

Secondary Outcome Measures

To investigate the effect of Velcade on the expression of NFkB, and biomarkers of NFkB

Including phosphorylation of c-Rel on leukaemic blasts by flow cytometry, protein analysis,

Immunohistochemistry, and/or mRNA profiling using gene and SNPs DNA chip.

Full Information

NCT ID

NCT00510939

First Posted

August 2, 2007

Last Updated

August 13, 2009

Sponsor

University of Bologna

Collaborators

Janssen-Cilag Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT00510939

Brief Title

Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Acute Myeloid Leukemia

Acronym

HEMOS AML 0106

Official Title

Phase II, Open-Label, Multi-centre, 2-part Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Unfit for Conventional Chemotherapy ( >18 Years) or in Patients With Acute Myeloid Leukemia in First Relapse ( >60 Years)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2009

Overall Recruitment Status

Unknown status

Study Start Date

March 2007 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

University of Bologna

Collaborators

Janssen-Cilag Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is one of the first studies of combination of Zarnestra plus Velcade in man. A primary objective of the study is therefore to assess the safety and tolerability of multiple doses of Zarnestra plus Velcade in patients with AML. New treatments for patients that are untreatable with intensive chemotherapy aged de novo AML patients or post-relapse AML are urgently required since, at present, many of the drugs used for second line therapy are the same as those used for first induction and response rates are much lower. The following evidence suggests that Velcade plus Zarnestra can be an attractive therapeutic combination for: AML patients. Affymetrix gene profiling data showed expression of NFkB1 in all of 5 myeloid cell lines cell lines tested and 35% of over 250 patient samples ( data generated in collaboration with Sergio Ferrari and Pier Paolo Piccaluga unpublished results, our Institute and University of Modena,Italy) Preclinical evidence showed that AML cells in suspension culture were prevented to develop de novo drug resistance and mediated drug resistance. In Part B additional patients with AML will be treated to further characterize the tolerability,biological effects, and clinical efficacy of the combination Velcade plus Zarnestra. Patients on treatment for AML will undergo regular bone marrow aspirates and biopsies to assess responses to treatment. This will facilitate frequent assessment of biological endpoints (reduction in expression and phosphorylation of IKKb kinase, and downstream markers of signalling along with apoptosis, survival, proliferation and cellular size and ploidy) will be made in an attempt to confirm that the desired biological activity has been achieved at the maximum tolerated dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

Acute myeloid leukemia, NFkB activity and leukemia, expression of NFkB

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Tipifarnib plus Bortezomib

Primary Outcome Measure Information:

Title

Time Frame

August 2007

Title

Time Frame

December 2008

Title

Time Frame

June 2010

Secondary Outcome Measure Information:

Title

To investigate the effect of Velcade on the expression of NFkB, and biomarkers of NFkB

Title

Including phosphorylation of c-Rel on leukaemic blasts by flow cytometry, protein analysis,

Title

Immunohistochemistry, and/or mRNA profiling using gene and SNPs DNA chip.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provision of written informed consent Male or female aged >18 years with newly diagnosed Acute Myeloid Leukemia (AML), de novo or secondary, unfit for conventional chemotherapy Male or female with Acute Myeloid Leukemia in first relapse ( > 60 years) WHO performance status ³ 2, or/and unwillingness to receive conventional chemotherapy Negative pregnancy test or evidence of post-menopausal status for female patients. RASGRP1/APTX gene expression ratio calculated at the screening >10 (part B.2 only) Exclusion Criteria: Serum bilirubin 2 x> Upper Limit of Normal (ULN) Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.5 x ULN Serum creatinine ³ 2.5 x ULN or 24-hour creatinine clearance £ 60 mL/min (measured or calculated by Cockcroft-Gault) Patients with AML of FAB M3 classification (APL) Patients with a history of another primary malignancy within the previous 1 year other than basal cell carcinoma or carcinoma in situ, the patient is in remission Any clinically defined central nervous system AML. Participation in an investigational drug study within the 30 days prior to entry Evidence of uncontrolled infection or CNS-Hemorrhagic Patients with documented cases of human immunodeficiency virus (HIV) Peripheral Neuropathy or Neuropathic Pain grade > or = 2 Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 7,NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis RASGRP1/APTX gene expression ratio calculated at the screening <10 (part B.2 only)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Giovanni Martinelli, MD

Phone

+39 051 6363829

gmartino@alma.unibo.it

First Name & Middle Initial & Last Name or Official Title & Degree

Barbara Lama, MD

Phone

+39 051 6363827

barbara.lama@unibo.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Giovanni Martinelli, MD

Organizational Affiliation

Istituto di Ematologia ed Oncologia Medica "L.eA.Seràgnoli" Policlinico S.Orsola-Malpighi di Bologna

Official's Role

Principal Investigator

Facility Information:

Facility Name

Istituto di Ematologia "L e A Seragnoli" Policlinico S.Orsola-Malpighi

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Giovanni Martinelli, MD

Phone

+039 051 6363829

martg@tin.it

12. IPD Sharing Statement

Learn more about this trial

Study to Assess the Safety, Tolerability, and Efficacy of Tipifarnib Plus Bortezomib in the Treatment of Acute Myeloid Leukemia

We'll reach out to this number within 24 hrs