Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

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.

NOX-A12

Kai Riecke, MD

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).

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.

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

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 safety evaluation will be based on the following assessments:

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

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.

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

The pharmacokinetics evaluation will be based on the following assessments:

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

TME Pharma AG

Lymphoma

Lymphosarcoma

Chromosome 17p Deletion

Venetoclax

Participants with 17p deletion status will receive various doses of venetoclax once daily (QD).

Participants who have failed a B-Cell Receptor Signaling Pathway Inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status will receive various doses of venetoclax once daily (QD).

ABBVIE CALL CENTER

ABBVIE INC.

This is a Phase 2, open-label, multicenter study, evaluating the efficacy of venetoclax in participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) either in presence of 17p deletion (Cohort 1) or those who have failed a B-receptor signaling pathway inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status (Cohort 2).

A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

ORR is the proportion of participants with an overall response (complete remission \[CR\], plus complete remission with incomplete bone marrow recovery \[CRi\], plus nodular partial remission \[nPR\], plus partial remission \[PR\]) per the National Cancer Institute-Working Group (NCI-WG) guidelines as assessed by the Independent Review Committee (IRC).

CRR is defined as the proportion of subjects who achieved (CR + CRi) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) NCI-WG criteria.

DOR is defined as the number of days from the date of first (CR + CRi + nPR + PR) to the earliest disease progression or death

PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC) or death.

EFS is defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy.

TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC).

Time to 50% reduction in ALC is defined as the number of days from the date of first dose to the date when the ALC has reduced to 50% of the baseline value.

OS is defined as number of days from the date of first dose to the date of death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
NOX-A12 in Combination With Bendamustine and Rituximab in Relapsed Chronic Lymphocytic Leukemia (CLL)	NCT01486797	Chronic Lymphoc...	NOX-A12	18 Years -	TME Pharma AG
A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	NCT02966756	Chronic Lymphoc... Small Lymphocyt...	Venetoclax	18 Years -	AbbVie

Spots Global Cancer Trial Database for relapsed chronic lymphocytic leukemia (cll)