NCT01521533

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_2 multiple-myeloma

Timeline
Completed

Started Mar 2012

Geographic Reach
4 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 26, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 30, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

March 1, 2012

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2015

Completed
Last Updated

October 6, 2015

Status Verified

October 1, 2015

Enrollment Period

2.5 years

First QC Date

January 26, 2012

Last Update Submit

October 5, 2015

Conditions

Multiple Myeloma

Keywords

Relapsed Multiple MyelomaNOX-A12VelcadeDexamethasoneSpiegelmerChemosensitizationStromal cell-derived factor-1 (SDF-1)CXCL12

Outcome Measures

Primary Outcomes (2)

  • Overall response rate (ORR = best response at least partial response (PR))

    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.

    6 months

  • Safety and tolerability of NOX A12 alone and in combination with VD

    The safety evaluation will be based on the following assessments: * Adverse events * Vital signs * 12 lead ECGs * Laboratory parameters * Abdominal ultrasound * Immunogenicity

    18 months

Secondary Outcomes (5)

  • Effect of NOX A12 alone and combined with VD on the mobilization of peripheral blood CD34+ cells, plasma cells and myeloma cells

    6 months

  • Additional response criteria such as Minor Response (MR), immunophenotypic Complete Response and molecular Complete Response

    6 months

  • 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

    18 months

  • Plasma concentration of SDF-1 after treatment with NOX-A12 alone (pilot group only) and in combination with VD

    6 months

  • Pharmacokinetics of NOX A12 alone (pilot group only) and combined with VD

    6 months

Study Arms (1)

NOX-A12

EXPERIMENTAL
Drug: NOX-A12

Interventions

NOX-A12DRUG

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.

Also known as: olaptesed
NOX-A12

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

University Hospital Salzburg, Department of Medicine III, Center of Oncology and Hematology

Salzburg, Austria

Location

Wilhelminenspital, Department of Medicine I, Center of Oncology and Hematology

Vienna, Austria

Location

Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille

Lille, France

Location

Hôpital Saint Antoine - Service des maladies du sang et de thérapie cellulaire

Paris, France

Location

University Hospital Freiburg, Medizinische Universitätsklinik, Innere Medizin I, Haematologie und Onkologie

Freiburg im Breisgau, Germany

Location

University Hospital Münster, Medizinische Klinik und Poliklinik A

Münster, Germany

Location

University Hospital Ulm, Zentrum für Innere Medizin,

Ulm, Germany

Location

University Hospital San Martino, Department of Hematology and Oncology

Genova, Italy

Location

Niguarda Ca'Granda Hospital, Department of Hematology

Milan, Italy

Location

Sapienza University of Rome, Department of Hematology

Rome, Italy

Location

Related Publications (1)

  • Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

    PMID: 30957581DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

NOX-A12

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Kai Riecke, MD

    TME Pharma AG

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 26, 2012

First Posted

January 30, 2012

Study Start

March 1, 2012

Primary Completion

September 1, 2014

Study Completion

September 1, 2015

Last Updated

October 6, 2015

Record last verified: 2015-10

Locations

IT(3)AU(2)FR(2)DE(3)