Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell

Leukemia, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

B-cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Amino Acids

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Bendamustine Hydrochloride

Rituximab

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

PCI-32765

Thorsten Graef, MD

The purpose of this study is to establish the safety of orally administered PCI-32765 in combination with fludarabine/cyclophosphamide/rituximab (FCR) and bendamustine/rituximab (BR) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma(SLL).

This is a Phase 1b, open-label, parallel-group, nonrandomized, multicenter study of PCI 32765 420 mg once daily oral (PO) administration in combination with 2 different chemotherapy regimens in subjects with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)

A Phase 1b, Multicenter, Open-label, Parallel-group Safety Study of a Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI 32765, in Combination With Chemotherapy in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size. Assessment of response to treatment will be done every 2 cycles for the first 6 months and then every 3 months thereafter until disease progression or prior to the administration of a new anticancer therapy and at follow-up visits.

Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size.

Pharmacyclics LLC.

PCI-32765 Plus Bendamustine/Rituximab (BR)

PCI-32765 Plus Fludarabine/ Cyclophosphamide/Rituximab (FCR)

PCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)

Total

Age, Continuous

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)

The FCR arm was discontinued due to very limited use of this chemo regimen in this setting, statistical analysis were limited due to the small numbers of subjects in this treatment arm.

Incidence of Prolonged Hematologic Toxicity Started in Cycle 1

Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib

Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0

Overall Incidence of Serious Adverse Events (SAEs)

Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])

No participants in the FCR group had neutropenia, anemia or thrombocytopenia at baseline.

Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline

PCI- 32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)

Progression Free Survival Rate at 12 Months

PCI-32765: 420 mg daily

FCR:

* Rituximab: 375 mg/m2 on Day 1 of Cycle 1 and a dose of 500 mg/m2 on Day 1(Cycle 2 to Cycle 6).
* Fludarabine: 25 mg/m2/day for 3 days (Days 1 to 3) of each cycle
* Cyclophosphamide: 250 mg/m2/day for 3 days (Days 1 to 3) of each cycle (Up to 6 Cycle)

PCI-32765: 420 mg daily

BR:

* Rituximab: 375 mg/m2 on Day 1 of Cycle 1 and a dose of 500 mg/m2 on Day 1 (Cycle 2 to Cycle 6).
* Bendamustine; 70 mg/m² on Day 1 and 2 of each cycle (Up to 6 Cycles)

Overall Study

Spots Global Cancer Trial Database for Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial