A Trial of Bevacizumab in Myelodysplastic Syndromes (Int-1, Int-2 and High Risk According to International Prognostic Scoring System (IPSS)) With Excess of Marrow Blasts

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT00565656
First received: November 28, 2007
Last updated: December 7, 2011
Last verified: June 2009
  Purpose

The objectives of this phase II trial are to test the efficacy and tolerance of Bevacizumab in MDS patients with excess of marrow blasts and to evaluate the impact of Bevacizumab on angiogenesis and erythropoiesis.

To limit the myelotoxicity observed in the preliminary phase II study, Bevacizumab will be administrated at the initial dose of 5 mg/kg.

The primary endpoint will be response: Complete Remission (CR), Partial Remission (PR) and hematological improvement (HI) according to IWG criteria (see appendix 3).

The secondary endpoints will be survival, response duration, side effects, evaluation of angiogenesis (bone marrow microvessel density, VEGF plasma level, VEGF mRNA expression, HIF-1alpha expression).

The design of this study consists of three study periods: pre-treatment (screening), treatment (loading and maintenance), and follow-up. All patients will participate in the study for at least 12 weeks of therapy, a 4-week follow-up visit, and long-term follow-up unless the criteria for planned or unplanned early discontinuation are met.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: BEVACIZUMAB
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Bevacizumab in Myelodysplastic Syndromes (Int-1, Int-2 and High Risk According to IPSS) With Excess of Marrow Blasts

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

Primary Outcome Measures:
  • Bone marrow evaluation Peripheral blood evaluation Cytogenetic response Hematologic improvement (HI) [ Time Frame: Before the first injection, weekly during twenty weeks and four weeks after the last injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary endpoints will be survival, side effects [ Time Frame: weekly ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: July 2007
Study Completion Date: July 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Bevacizumab
Drug: BEVACIZUMAB
Administration of Bevacizumab

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • MDS patient with excess of marrow blasts (≥ 5%) including RAEB, RAEB-t and CMML with leucocytes < 10 000/mm3 according to FAB classification
  • IPSS int-1, int-2 or high
  • Age > 60 years (younger adults may be included, but only in the absence of donor for allogeneic stem cell transplantation, and if contra-indication to intensive chemotherapy)
  • No previous allogeneic SCT or intensive anthracycline-Ara C chemotherapy.
  • Adequate renal function:

    • Serum creatinine ≤ 1.25 x ULN or calculated creatinine clearance ≥ 50 mL/min AND
    • Urine dipstick for proteinuria < 2+. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours
  • Adequate liver function:

    • Total bilirubin < 1.5 x upper limit of normal (ULN) AND Asparagine aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 x ULN in patients without liver metastases
  • International normalised ratio (INR) ≤1.5 and prothrombin time (PPT) ≤ 1.5 x ULN within 7 days prior to enrolment
  • If female, should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to enrollment into the study. If a serum pregnancy test is not performed within 7 days prior to the first dose of bevacizumab, a confirmatory urine test (within 7 days prior to the first dose of bevacizumab) is required.
  • Life expectancy ≥ 6 months
  • Patient with health insurance
  • Written informed consent

Exclusion Criteria:

  • Therapy related MDS (after chemo or radiotherapy) for a previous neoplasm or other disease including AML
  • A preexisting thrombocytopenia < 20 000/mm3
  • Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment or anticipation of the need for major surgery during study treatment
  • Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
  • Prior tumor (except localized cervix carcinoma or cutaneous basal cell carcinoma) unless in remission for at least 3 years.
  • Uncontrolled diabetes mellitus
  • Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (> 325 mg/day)
  • Uncontrolled hypertension (blood pressures: systolic > 150 mmHg and/or diastolic > 100 mmHg)
  • Clinically significant (i.e., active) cardiovascular disease for example CVA (≤6 months before enrollment), myocardial infarction (≤ 6 months before enrollment), unstable angina, congestive heart failure NYHA Class ≥ II, serious cardiac arrhythmia requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication
  • Non-healing wound, active peptic ulcer or bone fracture
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment
  • Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last administration of bevacizumab. Men who do not agree to use effective contraception during the study and for a period of 60 days following the last administration of bevacizumab
  • Investigational treatment for MDS within 6 weeks of treatment onset
  • Patients unable to give informed consent or to be followed up adequately
  • Known hypersensitivity to a product from Chinese Hamster Ovary mammalian cell or to a recombinant humanized monoclonal antibody
  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: NCT00565656

Locations
France
Department of clinical hematology
Avignon, France
Department of Hematology
Bobigny, France, 93009
Department of Hematology
Lyon, France, 69437
Paoli-Calmette Institut
Marseille, France, 13009
Department of Clinical hematology, Archet Hospital, CHU de Nice
Nice, France, 06000
Department of Onco-Hematology, Caremeau Hospital, CHU Nîmes
Nîmes, France, 30029
Department of clinical hematology, Robert Debré Hospital
Reims, France, 51092
Department of Hematology and Oncology, CHU de Strasbourg
Strasbourg, France, 67098
Service de Médecine Interne
Toulouse, France, 31059
Department of clinical hematology
Vandoeuvre, France, 54511
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Principal Investigator: Laurence LEGROS, Doctor Centre Hospitalier Universitaire de Nice
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT00565656     History of Changes
Other Study ID Numbers: 06-PP-05, AFSSAPS number:060748
Study First Received: November 28, 2007
Last Updated: December 7, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority
France: Institutional Ethical Committee

Keywords provided by Centre Hospitalier Universitaire de Nice:
Myelodysplastic syndromes (int-1, int-2 and high risk according to IPSS) with excess of marrow blasts including CMML with leucocytes<10 000/mm3

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014