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CompletedNCT01292135Updated Jul 24, 2014Results posted

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

A Phase 1 interventional study of PCI-32765 in B-cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, sponsored by Pharmacyclics LLC.. Completed at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-07-24.

Sponsored by Pharmacyclics LLC. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
33
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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).

Read the detailed description

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).

02

Conditions studied

  • B-cell Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma

Keywords

  • Lymphoma, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, B-Cell
  • Bruton's Tyrosine Kinase
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 33 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Pharmacyclics LLC. is the lead sponsor of 54 studies on the registry; none are open to participants now.

Of its 10 completed or terminated interventional studies of FDA-regulated products, 9 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Histologically confirmed CLL or SLL and satisfying at least 1 of the following criteria for requiring treatment:

    • Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies
    • Anemia (\<11 g/dL) or thrombocytopenia (\<100,000/μL) due to bone marrow involvement
    • Presence of unintentional weight loss > 10% over the preceding 6 months
    • NCI CTCAE Grade 2 or 3 fatigue
    • Fevers > 100.5° or night sweats for > 2 weeks without evidence of infection
    • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of \< 6 months
  2. 1 to 3 prior treatment regimens for CLL/SLL
  3. ECOG performance status of ≤ 1
  4. ≥ 18 years of age
  5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
  6. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Exclusion criteria

Exclusion Criteria:

  1. Any chemotherapy, therapeutic antineoplastic antibodies (not including radio- or toxin immunoconjugates), radiation therapy, or experimental antineoplastic therapy within 4 weeks of first dose of study drug
  2. Radio- or toxin-conjugated antibody therapy within 10 weeks of first dose of study drug
  3. Concomitant use of medicines known to cause QT prolongation or torsades de pointes
  4. Transformed lymphoma or Richter's transformation Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
  5. Any of the following laboratory abnormalities: oAbsolute neutrophil count (ANC) \< 1000 cells/mm3 (1.0 x 109/L) oPlatelet count \< 50,000/mm3 (50 x 109/L) oSerum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) oCreatinine > 2.0 x ULN or creatinine clearance \< 40 mL/min
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
33 participants (actual)

Study arms

  • Experimental
    PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR)

    Drug: PCI-32765

  • Experimental
    PCI-32765 plus bendamustine/rituximab (BR)

    Drug: PCI-32765

Interventions

  • DrugPCI-32765

    420 mg daily

06

What researchers measure

Primary outcomes

  1. Incidence of Prolonged Hematologic Toxicity Started in Cycle 1

    Time frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

Secondary outcomes

  1. Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib

    Time frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

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

    Time frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

  3. Overall Incidence of Serious Adverse Events (SAEs)

    Time frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.

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

    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.

    Time frame: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.

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

    Time frame: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.

  6. Progression Free Survival Rate at 12 Months

    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.

    Time frame: From first dose of any study medication to 12 months after first dose to progressive disease or death or the last clinical assessment before receiving new anticancer therapy or loss to follow-up, whichever occured the earliest.

07

Results

Posted Jul 24, 2014

Participant flow

Participant flow — Overall Study
MilestonePCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)PCI-32765 Plus Bendamustine/Rituximab (BR)
Started330
Completed321
Not completed09

Outcome measures

PrimaryIncidence of Prolonged Hematologic Toxicity Started in Cycle 1
Time frame:
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Reported as:
Number · Percentage of Participants
Incidence of Prolonged Hematologic Toxicity Started in Cycle 1
Percentage of ParticipantsPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
Incidence of Prolonged Hematologic Toxicity Started in Cycle 10 (0 to 11.6)0 (NA to NA)
SecondaryIncidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib
Time frame:
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Reported as:
Number · Percentage of Participants
Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib
Percentage of ParticipantsPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib53.333.3
SecondaryOverall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0
Time frame:
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Reported as:
Number · Percentage of Participants
Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0
Percentage of ParticipantsPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.066.70
SecondaryOverall Incidence of Serious Adverse Events (SAEs)
Time frame:
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Reported as:
Number · Percentage of Participants
Overall Incidence of Serious Adverse Events (SAEs)
Percentage of ParticipantsPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
Overall Incidence of Serious Adverse Events (SAEs)2033.3
SecondaryOverall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])

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.

Time frame:
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
Reported as:
Number · Percentage of Participants
Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])
Percentage of ParticipantsPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])93.3 (77.9 to 99.2)100 (NA to NA)
SecondarySustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline
Time frame:
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
Reported as:
Number · Percentage of Participants
Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline
Percentage of ParticipantsPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline76.2 (52.8 to 91.8)—
SecondaryProgression Free Survival Rate at 12 Months

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.

Time frame:
From first dose of any study medication to 12 months after first dose to progressive disease or death or the last clinical assessment before receiving new anticancer therapy or loss to follow-up, whichever occured the earliest.
Reported as:
Number · Percentage of Participants
Progression Free Survival Rate at 12 Months
Percentage of ParticipantsPCI-32765 Plus Bendamustine/Rituximab (BR)PCI- 32765 Plus Fludarabine/ Cyclophosphamide/ Rituximab (FCR)
Progression Free Survival Rate at 12 Months85.9 (66.7 to 94.5)100 (100 to 100)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PCI-32765 Plus Bendamustine/Rituximab (BR)—6/30 (20%)30/30 (100%)
PCI-32765 Plus Fludarabine/ Cyclophosphamide/Rituximab (FCR)—1/3 (33.3%)3/3 (100%)
Most frequent serious events
Most frequent serious events
EventPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/Rituximab (FCR)
GastritisGastrointestinal disorders0/301/3
Viral InfectionInfections and infestations0/301/3
Febrile neutropeniaBlood and lymphatic system disorders2/300/3
CellulitisInfections and infestations2/300/3
DehydrationMetabolism and nutrition disorders1/300/3
Tumour lysis syndromeMetabolism and nutrition disorders1/300/3
Most frequent other events
Showing 10 of 83
Most frequent other events
EventPCI-32765 Plus Bendamustine/Rituximab (BR)PCI-32765 Plus Fludarabine/ Cyclophosphamide/Rituximab (FCR)
HypocalcaemiaMetabolism and nutrition disorders3/303/3
DiarrhoeaGastrointestinal disorders21/301/3
ThrombocytopeniaBlood and lymphatic system disorders5/302/3
AnaemiaBlood and lymphatic system disorders2/302/3
NauseaGastrointestinal disorders20/302/3
HypomagnesaemiaMetabolism and nutrition disorders4/302/3
FatigueGeneral disorders14/300/3
NeutropeniaBlood and lymphatic system disorders12/301/3
Upper respiratory tract infectionInfections and infestations11/301/3
Dry mouthGastrointestinal disorders4/301/3

Baseline characteristics

Age, Continuous
Age, Continuous(Years)PCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)PCI-32765 Plus Bendamustine/Rituximab (BR)Total
Mean56.3 ± 1.5361.3 ± 9.5860.8 ± 9.24
Age, Categorical
Age, Categorical(Participants)PCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)PCI-32765 Plus Bendamustine/Rituximab (BR)Total
<=18 years000
Between 18 and 65 years31922
>=65 years01111
Sex: Female, Male
Sex: Female, Male(Participants)PCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)PCI-32765 Plus Bendamustine/Rituximab (BR)Total
Female055
Male32528
Region of Enrollment
Region of Enrollment(participants)PCI-32765 Plus Fludarabine/Cyclophosphamide/Rituximab (FCR)PCI-32765 Plus Bendamustine/Rituximab (BR)Total
United States33033
08

Study locations

6 sites
  • Dana Farber Cancer Center
    Boston, Massachusetts 02115, United States
  • CLL Research and Treatment Program
    New Hyde Park, New York 11042, United States
  • Weill Medical College of Cornell University
    New York, New York 10065, United States
  • University of Rochester
    Rochester, New York 14642, United States
  • Sarah Cannon Research Institute
    Nashville, Tennessee 37203, United States
  • MD Anderson
    Houston, Texas 77030, United States
09

References and documents

Publications

  • Brown JR, Barrientos JC, Barr PM, Flinn IW, Burger JA, Tran A, Clow F, James DF, Graef T, Friedberg JW, Rai K, O'Brien S. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood. 2015 May 7;125(19):2915-22. doi: 10.1182/blood-2014-09-585869. Epub 2015 Mar 9. PubMed 25755291 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 24, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01292135
Lead sponsor
Pharmacyclics LLC.
Responsible party
Sponsor
First posted
Feb 9, 2011
Start date
Feb 2011
Primary completion
Nov 2012
Completion
May 2013
Results posted
Jul 24, 2014
Last update
Jul 24, 2014

Study contacts

Thorsten Graef, MD
study director · Pharmacyclics LLC.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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