Velcade (Bortezomib - PS341) in the Treatment of Patients Over 18 Years With Ph+ Leukemia

This study has been completed.
Sponsor:
Information provided by:
University of Bologna
ClinicalTrials.gov Identifier:
NCT00511069
First received: August 2, 2007
Last updated: November 21, 2008
Last verified: November 2008
  Purpose

Ph+ leukemias (i.e.Chronic Myelogenous Leukemia (CML) and (Ph+) Acute Lymphoblastic Leukemia are malignant clonal disorder of the hemopoietic stem cell due to reciprocal translocation of genetic material between chromosome 9 and 22 giving rise to the translocation t(9;22) (q2.2; q2.1). The translocation causes the formation of a new hybrid gene (bcr-abl) that codes for a 185 kb or 210 kb cytoplasmic protein (P185 and P210 respectively) that by autophosphorylation activates a number of signaling pathways involved in cell proliferation, maturation, apoptosis and adhesion, leading to the malignant cell transformation1-3. The course of the disease goes on through a chronic phase (CP), usually lasting some years, that is characterized by a massive myeloid hyperplasia with hyperleukocytosis and splenomegaly. The CP is almost always followed by an accelerated or blastic phase (ABP) where the leukemic process acquires the characteristics of acute leukemia. The ABP usually lasts some months and terminates with the death of the patient3.

The frequency of CML in western countries ranges between 10 and 15 per million persons (age - standardized). It is rare in children. The median age is 55 years.

Current treatment of CML includes conventional chemotherapy, allogeneic bone marrow transplantation (allo BMT), alpha-interferon (alpha-IFN)and imatinib.


Condition Intervention Phase
Leukemia
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Velcade (Bortezomib - PS341) in the Treatment of Patients Over 18 Years With Ph+ Leukemia

Resource links provided by NLM:


Further study details as provided by University of Bologna:

Enrollment: 3
Study Start Date: July 2006
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for chronic phase patients :

  1. Age >/=18 years
  2. Ph positive
  3. Absence of a CHR after 3 months on imatinib
  4. Loss of a previously obtained CHR on imatinib alone
  5. Absence of a CCgR within 12 months on imatinib alone
  6. Loss of a previously obtained CCgR on imatinib alone
  7. Written informed consent

Exclusion Criteria for chronic phase patients :

  1. Age <18
  2. Performance status (ECOG/WHO) > 2 (see Appendix 2)
  3. Inability to provide written informed consent
  4. Pregnancy
  5. Accelerated or blastic phase
  6. Formal refusal of any recommendation of a safe contraception
  7. Alcohol or drug addiction
  8. Altered hepatic or renal function as defined by AST/ALT or bilirubin > 3 times upper normal limits (UNL)
  9. Serum creatinine > 265 umol/l or >3.0 mg/dl
  10. Any other disease or condition that by the advise of the responsible physician would make the treatment dangerous for the patient or would make the patient ineligible for the study, including physical, psychiatric, social and behavioural problems.

Inclusion criteria for accelerated and blastic phase or acute lymphoblastic leukemia Ph+ patients:

  1. Age >/=18 years
  2. Ph positive
  3. Loss of a previous hematological response to imatinib alone, with further progression to ABP (see section 14 for definitions)
  4. Performance status (ECOG/WHO)
  5. Written informed consent

Exclusion criteria for accelerated and blastic phase or acute lymphoblastic leukemia Ph+ patients:

  1. Age <18
  2. Performance status (ECOG/WHO) > 2 (see Appendix 2)
  3. Inability to provide written informed consent
  4. Pregnancy
  5. Chronic Phase disease
  6. Formal refusal of any recommendation of a safe contraception
  7. Alcohol or drug addiction
  8. Altered hepatic or renal function as defined by AST/ALT or bilirubin > 3 times upper normal limits (UNL)
  9. Serum creatinine > 265 umol/l or >3.0 mg/dl
  10. Any other disease or condition that by the advise of the responsible physician would make the treatment dangerous for the patient or would make the patient ineligible for the study, including physical, psychiatric, social and behavioural problems.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00511069

Locations
Italy
Policlinico "S.Orsola-Malpighi"-Istituto di Ematologia "L e A Seragnoli"
Bologna, Italy, 40138
Sponsors and Collaborators
University of Bologna
Investigators
Principal Investigator: Giovanni Martinelli, MD Istituto di Ematologia "L e A Seragnoli" Policlinico S.Orsola-Malpighi di Bologna
  More Information

No publications provided

Responsible Party: Giovanni Martinelli, Dipartimento di Ematologia "seragnoli"- Policlinico Sant'Orsola Bologna
ClinicalTrials.gov Identifier: NCT00511069     History of Changes
Other Study ID Numbers: CML/033-26866138-CAN, EUDRACT 2004-002977-22
Study First Received: August 2, 2007
Last Updated: November 21, 2008
Health Authority: Italy: The Italian Medicines Agency
Italy: Ethics Committee

Keywords provided by University of Bologna:
Bortezomib
CML033

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014