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A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic cells other
than T cells and is necessary for downstream signal transduction from various hematopoietic
receptors including the B cell receptor as well as some Fc, chemokine, and adhesion
receptors, and is crucial for both B cell development and osteoclastogenesis. Although
down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from
many myeloma patients and some cell lines. PCI 32765 is a potent and specific inhibitor of
Btk currently in Phase 2 clinical trials. The current study is designed and intended to
determine the effects of PCI-32765 in subjects with MM.

Optional Sub-Study:

Subjects entering the main study will be eligible to participate in an exploratory sub-study
to investigate possible mechanisms of treatment sensitivity and resistance. Bone marrow
specimens will be collected at three timepoints.

Inclusion Criteria:

- Diagnosis of symptomatic MM with measurable disease, defined here as having at least
one of the following:

1. Serum monoclonal protein (M-protein) ≥0.5 g/dL as determined by serum protein
electrophoresis (SPEP)

2. Urine M-protein ≥200 mg/24 hrs

3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L)
provided serum FLC ratio is abnormal

- Relapsed or relapsed and refractory MM after receiving at least 2 previous lines of
therapy, 1 of which must be an immunomodulator.

- Refractory myeloma (to most recent treatment) is defined as disease that is
nonresponsive while on treatment or progressive disease within 60 days after the
completion of preceding treatment. Nonresponsive disease is defined as either failure
to achieve minimal response or development of progressive disease while on therapy.

- Men and women ≥18 years of age.

- ECOG performance status of ≤ 1.

Exclusion Criteria:

- Subject must not have primary refractory disease defined as disease that is
nonresponsive in subjects who have never achieved a minor response (MR) or better
with any therapy.

- Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS)
syndrome, osteosclerotic myeloma, or Crow-Fukase syndrome.

- Plasma cell leukemia.

- Primary amyloidosis.

- Certain exclusions on prior therapy.

- ANC <0.75 x 10^9/L independent of growth factor support.

- Platelets <50 x 10^9/L) independent of transfusion support.

- AST or ALT ≥3.0 x upper limit of normal (ULN).

- Total bilirubin >2.5 x ULN, unless due to Gilbert's syndrome.

- Creatinine >2.5 mg/dL.

- Unable to swallow capsules or disease significantly affecting gastrointestinal

- Requires anti-coagulation with warfarin or a vitamin K antagonist. Requires treatment
with strong CYP3A4/5 inhibitors.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Efficacy as defined by clinical benefit rate

Outcome Description:

Participants will be followed until progression of disease or start of another anti-cancer treatment.

Outcome Time Frame:

Up to 24 Months

Safety Issue:


Principal Investigator

Thorsten Graef, MD, PHD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

March 2012

Completion Date:

July 2016

Related Keywords:

  • Multiple Myeloma
  • PCI-32765
  • Multiple Myeloma
  • Relapsed Refractory Multiple Myeloma
  • Bruton's Tyrosine Kinase
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Johns Hopkins University Baltimore, Maryland  21205
University of Michigan Ann Arbor, Michigan  48109-0624
Memorial Sloan Kettering Cancer Center New York, New York  10021
Fred Hutchinson Cancer Research Center Seattle, Washington  98109
Washington University School of Medicine Saint Louis, Missouri  63110
Hackensack University Medical Center Hackensack, New Jersey  07601
Mount Sinai Medical Center New York, New York  10029
University of Chicago Medical Center Chicago, Illinois  60637
Dana Farber Cancer Institute Boston, Massachusetts  02115
Sarah Cannon Research Institute Nashville, Tennessee  37203