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Trial record 2 of 6 for:    NOX-A12

NOX-A12 in Combination With Bortezomib and Dexamethasone in Relapsed Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01521533
Recruitment Status : Completed
First Posted : January 30, 2012
Last Update Posted : October 6, 2015
Information provided by (Responsible Party):

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: NOX-A12 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : March 2012
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: NOX-A12 Drug: NOX-A12

Pilot Group (NOX A12 single agent, and combined with VD):

  • 3 cohorts of 3 patients will receive treatment with NOX A12 alone at a single dose of 1, 2 or 4 mg/kg i.v. 2 weeks before the combination treatment of NOX A12 and VD will start. The combination of NOX A12 and VD will follow a dose titration design beginning at 1 mg/kg NOX A12 (cycle 1) proceeding to dose levels of 2 mg/kg (cycle 2) and 4 mg/kg (cycle 3) NOX A12 in combination with VD. This is followed by consolidation in cycles 4-8 when NOX-A12 will be kept at the highest individually titrated dose.

Expansion Group (NOX A12 in combination with VD):

  • Expansion patients will not receive single agent NOX-A12, but will receive combination treatment as for the pilot group.
Other Name: olaptesed

Primary Outcome Measures :
  1. Overall response rate (ORR = best response at least partial response (PR)) [ Time Frame: 6 months ]
    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.

  2. Safety and tolerability of NOX A12 alone and in combination with VD [ Time Frame: 18 months ]

    The safety evaluation will be based on the following assessments:

    • Adverse events
    • Vital signs
    • 12 lead ECGs
    • Laboratory parameters
    • Abdominal ultrasound
    • Immunogenicity

Secondary Outcome Measures :
  1. 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 ]
  2. Additional response criteria such as Minor Response (MR), immunophenotypic Complete Response and molecular Complete Response [ Time Frame: 6 months ]
  3. 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 ]
  4. Plasma concentration of SDF-1 after treatment with NOX-A12 alone (pilot group only) and in combination with VD [ Time Frame: 6 months ]
  5. Pharmacokinetics of NOX A12 alone (pilot group only) and combined with VD [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female, aged ≥ 18 years.
  2. Diagnosis of relapsed multiple myeloma for which bortezomib/dexamethasone would be given as standard of care.
  3. 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.
  4. Progressive disease according to International Myeloma Working Group criteria.
  5. Pre-study WHO Performance Status ≤ 2 and modified CIRS score of less than 7.
  6. Signed and dated, written informed consent.
  7. Men and women of reproductive potential must agree to follow accepted contraception methods during treatment and for 3 months after completion of treatment.
  8. Acceptable liver function: Bilirubin ≤ 1.5 x upper limit of normal (ULN).
  9. Acceptable hematology and hemostasis status: Platelet count ≥ 75 x 109/L, ANC > 0.75x109/L.
  10. Acceptable renal function: Serum creatinine ≤1.5 ULN and/or calculated creatinine clearance ≥ 50 mL/min (calculated according to Cockroft & Gault formula).
  11. No clinically significant abnormalities of liver volume, liver hemodynamics or elasticity, measured by abdominal ultrasound.

Exclusion Criteria:

  1. The patient has a history of, or is clinically suspicious for, cancer-related Central Nervous System disease.
  2. Prior allogeneic stem cell transplant (alloSCT) or patients who are considered to be candidates for alloSCT as assessed by their treating physician.
  3. 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.
  4. 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.
  5. Female patient is pregnant or breast-feeding.
  6. Known infection with HIV, active Hepatitis B or Hepatitis C.
  7. The patient has a history of prior toxicity from bortezomib or dexamethasone that resulted in permanent discontinuation of respective treatments.
  8. Clinical evidence of a current significant (grade 2 or higher) or progressive neuropathy.
  9. Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to study drug administration.
  10. Uncontrolled hypertension (defined as systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm Hg).
  11. 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.
  12. Evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation).
  13. 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.
  14. Known or suspected of not being able to comply with the trial protocol.
  15. Having been previously enrolled in this clinical trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01521533

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University Hospital Salzburg, Department of Medicine III, Center of Oncology and Hematology
Salzburg, Austria
Wilhelminenspital, Department of Medicine I, Center of Oncology and Hematology
Vienna, Austria
Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille
Lille, France
Hôpital Saint Antoine - Service des maladies du sang et de thérapie cellulaire
Paris, France
University Hospital Freiburg, Medizinische Universitätsklinik, Innere Medizin I, Haematologie und Onkologie
Freiburg, Germany
University Hospital Münster, Medizinische Klinik und Poliklinik A
Münster, Germany
University Hospital Ulm, Zentrum für Innere Medizin,
Ulm, Germany
University Hospital San Martino, Department of Hematology and Oncology
Genova, Italy
Niguarda Ca'Granda Hospital, Department of Hematology
Milano, Italy
Sapienza University of Rome, Department of Hematology
Rome, Italy
Sponsors and Collaborators
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Study Director: Kai Riecke, MD NOXXON Pharma AG
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: NOXXON Pharma AG Identifier: NCT01521533    
Other Study ID Numbers: SNOXA12C301
2011-004651-40 ( EudraCT Number )
First Posted: January 30, 2012    Key Record Dates
Last Update Posted: October 6, 2015
Last Verified: October 2015
Keywords provided by NOXXON Pharma AG:
Relapsed Multiple Myeloma
Stromal cell-derived factor-1 (SDF-1)
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases