- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01521533
NOX-A12 in Combination With Bortezomib and Dexamethasone in Relapsed Multiple Myeloma
October 5, 2015 updated by: TME Pharma AG
A Multi-center, Open Label, Uncontrolled, Phase IIA Clinical Trial Evaluating the Safety and Efficacy of NOX A12 in Combination With a Background Therapy of Bortezomib and Dexamethasone (VD) in Previously Treated Patients With Multiple Myeloma (MM)
The purpose of this study is to evaluate the safety and efficacy of NOX A12 alone and in combination with a background therapy of bortezomib and dexamethasone (VD) chemotherapy in previously treated patients with multiple myeloma (MM).
Study Overview
Detailed Description
Malignant plasma cells express high levels of CXCR4 chemokine receptors, which cause cell migration and adhesion to stromal cells secreting the CXCR4 ligand, CXCL12 (SDF-1).
NOX A12 is a specific CXCL12 antagonist and may improve chemotherapy by disrupting CXCR4-CXCL12 interactions, thereby mobilizing plasma cells from protective tissue microenvironments to the blood.
Furthermore, SDF-1 inhibition may alter the activation status of plasma cells, thereby triggering apoptosis or sensitization of plasma cells towards chemotherapy.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Salzburg, Austria
- University Hospital Salzburg, Department of Medicine III, Center of Oncology and Hematology
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Vienna, Austria
- Wilhelminenspital, Department of Medicine I, Center of Oncology and Hematology
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Lille, France
- Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille
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Paris, France
- Hôpital Saint Antoine - Service des maladies du sang et de thérapie cellulaire
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Freiburg, Germany
- University Hospital Freiburg, Medizinische Universitätsklinik, Innere Medizin I, Haematologie und Onkologie
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Münster, Germany
- University Hospital Münster, Medizinische Klinik und Poliklinik A
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Ulm, Germany
- University Hospital Ulm, Zentrum für Innere Medizin,
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Genova, Italy
- University Hospital San Martino, Department of Hematology and Oncology
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Milano, Italy
- Niguarda Ca'Granda Hospital, Department of Hematology
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Rome, Italy
- Sapienza University of Rome, Department of Hematology
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female, aged ≥ 18 years.
- Diagnosis of relapsed multiple myeloma for which bortezomib/dexamethasone would be given as standard of care.
- Bortezomib-naïve or bortezomib-sensitive patient (i.e. best response of PR or better, sustained for at least 6 months), who did not receive bortezomib during the last line of therapy for MM prior to this study.
- Progressive disease according to International Myeloma Working Group criteria.
- Pre-study WHO Performance Status ≤ 2 and modified CIRS score of less than 7.
- Signed and dated, written informed consent.
- Men and women of reproductive potential must agree to follow accepted contraception methods during treatment and for 3 months after completion of treatment.
- Acceptable liver function: Bilirubin ≤ 1.5 x upper limit of normal (ULN).
- Acceptable hematology and hemostasis status: Platelet count ≥ 75 x 109/L, ANC > 0.75x109/L.
- Acceptable renal function: Serum creatinine ≤1.5 ULN and/or calculated creatinine clearance ≥ 50 mL/min (calculated according to Cockroft & Gault formula).
- No clinically significant abnormalities of liver volume, liver hemodynamics or elasticity, measured by abdominal ultrasound.
Exclusion Criteria:
- The patient has a history of, or is clinically suspicious for, cancer-related Central Nervous System disease.
- Prior allogeneic stem cell transplant (alloSCT) or patients who are considered to be candidates for alloSCT as assessed by their treating physician.
- Patient has a history of other active malignancies within 3 years prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma of the skin; in situ carcinoma of the bladder; previous malignancy confined and surgically resected with curative intent.
- The patient exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal); diagnosis of fever and neutropenia within 1 week prior to study drug administration.
- Female patient is pregnant or breast-feeding.
- Known infection with HIV, active Hepatitis B or Hepatitis C.
- The patient has a history of prior toxicity from bortezomib or dexamethasone that resulted in permanent discontinuation of respective treatments.
- Clinical evidence of a current significant (grade 2 or higher) or progressive neuropathy.
- Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to study drug administration.
- Uncontrolled hypertension (defined as systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm Hg).
- Myocardial infarction or unstable angina within the past 6 months prior to study drug administration. Heart failure of New York Heart Association functional Class III or IV prior to study drug administration.
- Evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation).
- Systemic illnesses or other severe concurrent disease or alcoholism, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and efficacy of the investigational treatments.
- Known or suspected of not being able to comply with the trial protocol.
- Having been previously enrolled in this clinical trial.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: NOX-A12
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Pilot Group (NOX A12 single agent, and combined with VD):
Expansion Group (NOX A12 in combination with VD):
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall response rate (ORR = best response at least partial response (PR))
Time Frame: 6 months
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Assessment of the overall tumor response after cycle 4 and 8 will be the primary efficacy endpoint.
The recommendations for the uniform reporting of clinical trials as published by the International Myeloma Workshop Consensus Panel 1 in 2011 will be applied.
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6 months
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Safety and tolerability of NOX A12 alone and in combination with VD
Time Frame: 18 months
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The safety evaluation will be based on the following assessments:
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18 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Effect of NOX A12 alone and combined with VD on the mobilization of peripheral blood CD34+ cells, plasma cells and myeloma cells
Time Frame: 6 months
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6 months
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Additional response criteria such as Minor Response (MR), immunophenotypic Complete Response and molecular Complete Response
Time Frame: 6 months
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6 months
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Time to event endpoints such as Progression Free Survival (PFS), Time To Progression (TTP) and Duration Of Response (DOR) following treatment with NOX A12 in combination with VD
Time Frame: 18 months
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18 months
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Plasma concentration of SDF-1 after treatment with NOX-A12 alone (pilot group only) and in combination with VD
Time Frame: 6 months
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6 months
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Pharmacokinetics of NOX A12 alone (pilot group only) and combined with VD
Time Frame: 6 months
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6 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2012
Primary Completion (ACTUAL)
September 1, 2014
Study Completion (ACTUAL)
September 1, 2015
Study Registration Dates
First Submitted
January 26, 2012
First Submitted That Met QC Criteria
January 26, 2012
First Posted (ESTIMATE)
January 30, 2012
Study Record Updates
Last Update Posted (ESTIMATE)
October 6, 2015
Last Update Submitted That Met QC Criteria
October 5, 2015
Last Verified
October 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
Other Study ID Numbers
- SNOXA12C301
- 2011-004651-40 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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