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

NCT ID: NCT00510939

Last Updated: 2009-08-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31

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and 35% of over 250 patient samples ( data generated in collaboration with Sergio Ferrari and Pier Paolo Piccaluga unpublished results, our Institute and University of Modena,Italy)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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Tipifarnib plus Bortezomib

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of written informed consent

2. Male or female aged >18 years with newly diagnosed Acute Myeloid Leukemia (AML), de novo or secondary, unfit for conventional chemotherapy

3. Male or female with Acute Myeloid Leukemia in first relapse ( > 60 years)

4. WHO performance status ³ 2, or/and unwillingness to receive conventional chemotherapy

5. Negative pregnancy test or evidence of post-menopausal status for female patients.

6. RASGRP1/APTX gene expression ratio calculated at the screening >10 (part B.2 only)

Exclusion Criteria

1. Serum bilirubin 2 x> Upper Limit of Normal (ULN)

2. Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) >3.5 x ULN

3. Serum creatinine ³ 2.5 x ULN or 24-hour creatinine clearance £ 60 mL/min (measured or calculated by Cockcroft-Gault)

4. Patients with AML of FAB M3 classification (APL)

5. 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

6. Any clinically defined central nervous system AML.

7. Participation in an investigational drug study within the 30 days prior to entry

8. Evidence of uncontrolled infection or CNS-Hemorrhagic

9. Patients with documented cases of human immunodeficiency virus (HIV)

10. Peripheral Neuropathy or Neuropathic Pain grade > or = 2

11. Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used

12. 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

13. RASGRP1/APTX gene expression ratio calculated at the screening <10 (part B.2 only)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

University of Bologna

OTHER

Sponsor Role: lead

Responsible Party

Dipartimento di Ematologia "Seragnoli"- Policlinico Sant'Orsola Bologna

Principal Investigators

Giovanni Martinelli, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Bologna, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Giovanni Martinelli, MD

Role: CONTACT

gmartino@alma.unibo.it

+39 051 6363829

Barbara Lama, MD

Role: CONTACT

barbara.lama@unibo.it

+39 051 6363827

Facility Contacts

Giovanni Martinelli, MD

Role: primary

martg@tin.it

+039 051 6363829

Other Identifiers

EudraCT 2007-000273-35

Identifier Type: -

Identifier Source: secondary_id

HEMOS AML 0106

Identifier Type: -

Identifier Source: org_study_id