NCT01486797

Brief 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).

Trial Health

90
On Track

Trial Health Score

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

Enrollment
28

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2012

Longer than P75 for phase_2

Geographic Reach
4 countries

17 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

December 1, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 7, 2011

Completed
3 months until next milestone

Study Start

First participant enrolled

March 1, 2012

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2014

Completed
2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
Last Updated

May 22, 2017

Status Verified

May 1, 2017

Enrollment Period

2.7 years

First QC Date

December 1, 2011

Last Update Submit

May 19, 2017

Conditions

Chronic Lymphocytic Leukemia

Keywords

Relapsed Chronic Lymphocytic Leukemia (CLL)NOX-A12BendamustineRituximabSpiegelmerChemosensitizationStromal cell-derived factor-1 (SDF-1)CXCL12

Outcome Measures

Primary Outcomes (2)

  • 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

    30 months

  • 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.

    6 months

Secondary Outcomes (8)

  • Pharmacodynamics of NOX-A12 alone and in combination with BR

    6 months

  • Overall response rate (ORR = CR + PR)

    6 months

  • Progression free survival (PFS)

    30 months

  • Pharmacokinetics of NOX-A12 alone and in combination with BR

    10 time points over 6 months

  • Event free survival (EFS)

    30 months

  • +3 more secondary outcomes

Study Arms (1)

NOX-A12

EXPERIMENTAL
Drug: NOX-A12

Interventions

NOX-A12DRUG

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.

Also known as: olaptesed pegol
NOX-A12

Eligibility Criteria

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

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • 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.
  • 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.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Medical University Innsbruck, Division of Hematology and Oncology

Innsbruck, Austria

Location

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

Salzburg, Austria

Location

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

Steyr, Austria

Location

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

Wels, Austria

Location

Cliniques universitaires Saint-Luc

Brussels, Belgium

Location

Institute Jules Bordet, Department of Hematology

Brussels, Belgium

Location

University Hospital Gasthuisberg, Department of Hematology

Leuven, Belgium

Location

Centre Hospitalier Universitaire Clémenceau, Department of Hematology

Caen, France

Location

Hospices Civils, Department of Hematology

Lyon, France

Location

Centre Hospitalier Universitaire de la Milétrie, Department of Hematology

Poitiers, France

Location

University Hospital, Institute of Hematology and Oncology

Bologna, Italy

Location

Azienda Sanitaria Locale 8, Department of Oncology

Cagliari, Italy

Location

University Hospital San Martino, Department of Hematology and Oncology

Genova, Italy

Location

Niguarda Ca'Granda Hospital

Milan, Italy

Location

University Scientific Research Institute San Raffaele

Milan, Italy

Location

University School of Medicine, Department of Hematology

Padua, Italy

Location

University La Sapienza, Department of Cellular Biotechnologies and Hematology

Rome, Italy

Location

Related Publications (2)

  • 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.

    PMID: 31097627DERIVED

  • 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

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

NOX-A12

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

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

December 1, 2011

First Posted

December 7, 2011

Study Start

March 1, 2012

Primary Completion

November 1, 2014

Study Completion

April 1, 2017

Last Updated

May 22, 2017

Record last verified: 2017-05

Locations

BE(3)FR(3)AU(4)IT(7)