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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
NOXXON Pharma AG
ClinicalTrials.gov Identifier:
NCT01521533
First received: January 26, 2012
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Multiple Myeloma
Drug: NOX-A12
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by NOXXON Pharma AG:

Primary Outcome Measures:
  • Overall response rate (ORR = best response at least partial response (PR)) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Safety and tolerability of NOX A12 alone and in combination with VD [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

    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:
  • 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 ] [ Designated as safety issue: No ]
  • Additional response criteria such as Minor Response (MR), immunophenotypic Complete Response and molecular Complete Response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Plasma concentration of SDF-1 after treatment with NOX-A12 alone (pilot group only) and in combination with VD [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of NOX A12 alone (pilot group only) and combined with VD [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: March 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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.
  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: NCT01521533

Locations
Austria
Medical University Innsbruck, Division of Hematology and Oncology
Innsbruck, Austria
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
France
Hôpital d'Enfants, Centre Hospitalier Universitaire, Hématologie clinique
Dijon, France
Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille
Lille, France
Institut Paoli-Calmettes Département d'hématologie
Marseille, France
Centre Hospitalier Universitaire Hotêl Dieu, Hematologie Clinique
Nantes, France
Hôpital Saint Antoine - Service des maladies du sang et de thérapie cellulaire
Paris, France
Centre Hospitalier Universitaire Hôpital Bretonneau, Département d'hématologie
Tours, France
Germany
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 Würzburg, Hämatologie/Onkologie und Early Clinical Trial Unit (ECTU) Zentrum für Innere Medizin (ZIM)
Würzburg, Germany
Italy
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
NOXXON Pharma AG
Investigators
Study Director: Kai Riecke, MD NOXXON Pharma AG
  More Information

No publications provided

Responsible Party: NOXXON Pharma AG
ClinicalTrials.gov Identifier: NCT01521533     History of Changes
Other Study ID Numbers: SNOXA12C301, 2011-004651-40
Study First Received: January 26, 2012
Last Updated: June 25, 2014
Health Authority: Italy: The Italian Medicines Agency
Austria: Austrian Medicines and Medical Devices Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by NOXXON Pharma AG:
Relapsed Multiple Myeloma
NOX-A12
Velcade
Dexamethasone
Spiegelmer
Chemosensitization
Stromal cell-derived factor-1 (SDF-1)
CXCL12

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on July 22, 2014