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Chronic Lymphocytic LeukemiaPhase 2NCT01486797

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

A Phase 2 study testing NOX-A12 in people with Chronic Lymphocytic Leukemia, run by TME Pharma AG at 17 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
NOX-A12
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
17 sitesin 4 countries
Study dates
Mar 2012to Apr 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of B-cell CLL
  • 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.
  • CLL in need of treatment (Binet C or A/B with active disease) according to Hallek et al. 2008
  • Subject must have measurable disease according to NCI-WG criteria (for details see Hallek M, Blood 2008; 111: 5446-5456).
  • Pre-study WHO performance status ≤ 2 and modified cumulative illness rating score (CIRS) of less than 7.
  • Signed, written informed consent.
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  • Men and women of reproductive potential must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment.
  • Acceptable liver function: Bilirubin ≤ 1.5 x upper limit of normal (ULN) at screening, AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x ULN.
  • Acceptable hematologic status: Platelet count ≥ 75 x 109/L, ANC > 0.75x109/L.
  • Acceptable renal function: Serum creatinine ≤1.5 ULN and/or calculated creatinine clearance (Cockroft-Gault Formula) ≥ 50 mL/min
  • Male or female, age ≥ 18
  • No clinically significant abnormalities of liver volume, liver hemodynamics or elasticity, measured by abdominal ultrasound.

Who cannot join

  • Relapse of B-cell CLL within 12 months after last chemotherapy.
  • Subjects who have progressed to more aggressive B-cell cancers such as Richter's syndrome.
  • CLL with documented loss of the short arm of chromosome 17 (17p-) associated with the loss of p53.
  • The subject has a history of or is clinically suspicious for cancer-related Central Nervous System disease.
  • Patients at risk of hemostasis or spleen rupture.
  • Autoimmune hemolytic anemia.
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  • Prior allogeneic stem cell transplant (alloSCT) or patients who are considered to be candidates for allo SCT as assessed by their treating physician
  • 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.
  • 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 subject is pregnant or breast-feeding.
  • Known infection with HIV, active Hepatitis B or Hepatitis C.
  • The patient has a history of prior toxicity from bendamustine or rituximab that resulted in permanent discontinuation of treatments.
  • Treatment with other investigational drugs, 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.
  • 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.
  • Known or suspected of not being able to comply with the trial protocol.
  • Having been previously enrolled in this clinical trial.
  • Known hypersensitivity to rituximab or to any of the excipients or to murine proteins
  • History of recurring or chronic infections or underlying conditions which may further predispose patients to serious infection.
  • Known hypersensitivity to bendamustine or to mannitol.
  • Invasive surgery within 30 days prior to study drug administration.

Trial locations and contacts

17 sites in 4 countries.

17 sites in 4 countries

Italy7 sites

  • University Hospital, Institute of Hematology and Oncology

    Bologna

  • Azienda Sanitaria Locale 8, Department of Oncology

    Cagliari

  • University Hospital San Martino, Department of Hematology and Oncology

    Genova

  • Niguarda Ca'Granda Hospital

    Milan

  • University Scientific Research Institute San Raffaele

    Milan

  • University School of Medicine, Department of Hematology

    Padova

  • University La Sapienza, Department of Cellular Biotechnologies and Hematology

    Rome

Other trials in Italy

Austria4 sites

  • Medical University Innsbruck, Division of Hematology and Oncology

    Innsbruck

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

    Salzburg

  • Landeskrankenhaus Steyr, Department of Internal Medicine II (Hematology and Oncology)

    Steyr

  • Hospital Wels-Grieskrichen, Department of Internal Medicine IV (Hematology and Oncology)

    Wels

Other trials in Austria

Belgium3 sites

  • Cliniques universitaires Saint-Luc

    Brussels

  • Institute Jules Bordet, Department of Hematology

    Brussels

  • University Hospital Gasthuisberg, Department of Hematology

    Leuven

Other trials in Belgium

France3 sites

  • Centre Hospitalier Universitaire Clémenceau, Department of Hematology

    Caen

  • Hospices Civils, Department of Hematology

    Lyon

  • Centre Hospitalier Universitaire de la Milétrie, Department of Hematology

    Poitiers

Other trials in France

About this study

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 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).

Read the 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.

Being tested
NOX-A12
Keywords
Relapsed Chronic Lymphocytic Leukemia (CLL), NOX-A12, Bendamustine, Rituximab, Spiegelmer, Chemosensitization, Stromal cell-derived factor-1 (SDF-1), CXCL12
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NOX-A12Drug

    Also called olaptesed pegol

    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.
Study groups in NCT01486797
Study groupRoleWhat they receive
NOX-A12ExperimentalNot described
Receives: Drug: NOX-A12

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of NOX A12 alone and in combination with BR.

    The safety evaluation will be based on the following assessments:

    • adverse events
    • vital signs
    • 12 lead ECGs
    • laboratory parameters
    • immunogenicity

    Measured: 30 months

  2. Complete remission (CR) rate

    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.

    Measured: 6 months

Secondary outcomes (8)

  1. Pharmacodynamics of NOX-A12 alone and in combination with BR

    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

    Measured: 6 months

  2. Overall response rate (ORR = CR + PR)

    Measured: 6 months

  3. Progression free survival (PFS)

    Measured: 30 months

  4. Pharmacokinetics of NOX-A12 alone and in combination with BR

    The pharmacokinetics evaluation will be based on the following assessments:

    • plasma concentration of NOX-A12
    • 24-hour urine excretion of NOX-A12

    Measured: 10 time points over 6 months

  5. Event free survival (EFS)

    Measured: 30 months

  6. Time to progression (TTP)

    Measured: 30 months

  7. Duration of response (DOR)

    Measured: 30 months

  8. Overall survival (OS)

    Measured: 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2011 (estimated)
  2. Study startMar 2012
  3. Primary completionNov 2014
  4. Study completionApr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01486797
Sponsor's protocol ID
SNOXA12C201
Other IDs
2011-004672-11
Status last verified
May 2017
First submitted
1 Dec 2011
Last updated
22 May 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Steurer M, Montillo M, Scarfo L, Mauro FR, Andel J, Wildner S, Trentin L, Janssens A, Burgstaller S, Fromming A, Dummler T, Riecke K, Baumann M, Beyer D, Vauleon S, Ghia P, Foa R, Caligaris-Cappio F, Gobbi M. Olaptesed pegol (NOX-A12) with bendamustine and rituximab: a phase IIa study in patients with relapsed/refractory chronic lymphocytic leukemia. Haematologica. 2019 Oct;104(10):2053-2060. doi: 10.3324/haematol.2018.205930. Epub 2019 May 16.

    PubMed 31097627

  • 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.

    PubMed 30957581

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NOX-A12 in people with Chronic Lymphocytic Leukemia, run by TME Pharma AG at 17 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Italy, Austria, Belgium, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability of NOX A12 alone and in combination with BR. (time frame: 30 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01486797, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2017.

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