NOX-A12 in Combination With Bendamustine and Rituximab in Relapsed Chronic Lymphocytic Leukemia (CLL)

May 19, 2017 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 Bendamustine and Rituximab (BR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)

The purpose of this study is to evaluate the safety and efficacy of NOX A12 in combination with a background therapy of bendamustine and rituximab (BR) chemotherapy in previously treated patients with chronic lymphocytic leukemia (CLL).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

CLL cells express high levels of CXCR4 chemokine receptors, which cause leukemia cell migration and adhesion to stromal cells secreting the CXCR4 ligand, CXCL12 (or stromal-derived-factor 1, SDF-1). NOX A12 is a specific CXCL12 antagonist and may improve BR therapy by disrupting CXCR4-CXCL12 interactions, thereby mobilizing CLL cells from protective tissue microenvironments to the blood. Furthermore, SDF-1 inhibition may alter the activation status of CLL cells, thereby triggering apoptosis or sensitization of CLL cells towards chemotherapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Austria
      • Innsbruck, Austria
        • Medical University Innsbruck, Division of Hematology and Oncology
      • Salzburg, Austria
        • University Hospital Salzburg, Department of Medicine III, Center of Oncology and Hematology
      • Steyr, Austria
        • Landeskrankenhaus Steyr, Department of Internal Medicine II (Hematology and Oncology)
      • Wels, Austria
        • Hospital Wels-Grieskrichen, Department of Internal Medicine IV (Hematology and Oncology)
  • Belgium
      • Brussels, Belgium
        • Cliniques universitaires Saint-Luc
      • Brussels, Belgium
        • Institute Jules Bordet, Department of Hematology
      • Leuven, Belgium
        • University Hospital Gasthuisberg, Department of Hematology
  • France
      • Caen, France
        • Centre Hospitalier Universitaire Clémenceau, Department of Hematology
      • Lyon, France
        • Hospices Civils, Department of Hematology
      • Poitiers, France
        • Centre Hospitalier Universitaire de la Milétrie, Department of Hematology
  • Italy
      • Bologna, Italy
        • University Hospital, Institute of Hematology and Oncology
      • Cagliari, Italy
        • Azienda Sanitaria Locale 8, Department of Oncology
      • Genova, Italy
        • University Hospital San Martino, Department of Hematology and Oncology
      • Milano, Italy
        • Niguarda Ca'Granda Hospital
      • Milano, Italy
        • University Scientific Research Institute San Raffaele
      • Padova, Italy
        • University School of Medicine, Department of Hematology
      • Rome, Italy
        • University La Sapienza, Department of Cellular Biotechnologies and Hematology

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of B-cell CLL
  2. Relapsed, bendamustine-sensitive (at least partial response with a duration of at least six months) or bendamustine-naive patients after at least one but not more than 3 prior treatments of their disease.
  3. CLL in need of treatment (Binet C or A/B with active disease) according to Hallek et al. 2008
  4. Subject must have measurable disease according to NCI-WG criteria (for details see Hallek M, Blood 2008; 111: 5446-5456).
  5. Pre-study WHO performance status ≤ 2 and modified cumulative illness rating score (CIRS) of less than 7.
  6. Signed, written informed consent.
  7. Men and women of reproductive potential must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment.
  8. Acceptable liver function: Bilirubin ≤ 1.5 x upper limit of normal (ULN) at screening, AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x ULN.
  9. Acceptable hematologic 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 (Cockroft-Gault Formula) ≥ 50 mL/min
  11. Male or female, age ≥ 18
  12. No clinically significant abnormalities of liver volume, liver hemodynamics or elasticity, measured by abdominal ultrasound.

Exclusion Criteria:

  1. Relapse of B-cell CLL within 12 months after last chemotherapy.
  2. Subjects who have progressed to more aggressive B-cell cancers such as Richter's syndrome.
  3. CLL with documented loss of the short arm of chromosome 17 (17p-) associated with the loss of p53.
  4. The subject has a history of or is clinically suspicious for cancer-related Central Nervous System disease.
  5. Patients at risk of hemostasis or spleen rupture.
  6. Autoimmune hemolytic anemia.
  7. Prior allogeneic stem cell transplant (alloSCT) or patients who are considered to be candidates for allo SCT as assessed by their treating physician
  8. Patient has a history of other active malignancies within three 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.
  9. 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.
  10. Female subject is pregnant or breast-feeding.
  11. Known infection with HIV, active Hepatitis B or Hepatitis C.
  12. The patient has a history of prior toxicity from bendamustine or rituximab that resulted in permanent discontinuation of treatments.
  13. Treatment with other investigational drugs, or participation in another clinical trial within 30 days prior to study drug administration.
  14. Uncontrolled hypertension (defined as systolic blood pressure (BP) > 160 mm Hg or diastolic BP > 100 mm Hg).
  15. Myocardial infarction or unstable angina within the past 6 months prior to study drug administration.
  16. Systemic illnesses or other severe concurrent disease including 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.
  17. Known or suspected of not being able to comply with the trial protocol.
  18. Having been previously enrolled in this clinical trial.
  19. Known hypersensitivity to rituximab or to any of the excipients or to murine proteins
  20. History of recurring or chronic infections or underlying conditions which may further predispose patients to serious infection.
  21. Known hypersensitivity to bendamustine or to mannitol.
  22. Invasive surgery within 30 days prior to study drug administration.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: NOX-A12
Drug: NOX-A12

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

  • 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 BR begins.The combination of NOX-A12 and BR 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 BR. This is followed by consolidation in cycles 4-6 when NOX-A12 will be kept at the highest individually titrated dose.

Expansion Group (NOX-A12 in combination with BR):

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability of NOX A12 alone and in combination with BR.
Time Frame: 30 months

The safety evaluation will be based on the following assessments:

  • adverse events
  • vital signs
  • 12 lead ECGs
  • laboratory parameters
  • immunogenicity
30 months
Complete remission (CR) rate
Time Frame: 6 months
Assessment of the complete remission rate after cycle 3 and 6 will be the primary efficacy endpoint. The 1996 NCI-WG criteria which have been updated in 2008 will be applied.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 30 months
30 months
Pharmacodynamics of NOX-A12 alone and in combination with BR
Time Frame: 6 months

The pharmacodynamics evaluation will be based on the following assessments:

  • mobilization of peripheral blood CD34+ cells and CLL cells
  • plasma concentration of SDF-1/CXCL12
6 months
Overall response rate (ORR = CR + PR)
Time Frame: 6 months
6 months
Progression free survival (PFS)
Time Frame: 30 months
30 months
Pharmacokinetics of NOX-A12 alone and in combination with BR
Time Frame: 10 time points over 6 months

The pharmacokinetics evaluation will be based on the following assessments:

  • plasma concentration of NOX-A12
  • 24-hour urine excretion of NOX-A12
10 time points over 6 months
Event free survival (EFS)
Time Frame: 30 months
30 months
Time to progression (TTP)
Time Frame: 30 months
30 months
Duration of response (DOR)
Time Frame: 30 months
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
TME Pharma AG

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.

General Publications

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 1, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 7, 2011

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 22, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SNOXA12C201
  • 2011-004672-11 (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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