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A Phase I Study of Carfilzomib in Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)/Prolymphocytic Leukemia (PLL)


Phase 1
18 Years
N/A
Open (Enrolling)
Both
B-cell Chronic Lymphocytic Leukemia, Hematopoietic/Lymphoid Cancer, Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia

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Trial Information

A Phase I Study of Carfilzomib in Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)/Prolymphocytic Leukemia (PLL)


PRIMARY OBJECTIVES:

I. To determine the dose limiting toxicity (DLT) and maximal tolerated dose (MTD) of
carfilzomib in patients with relapsed or refractory Chronic Lymphocytic Leukemia(CLL) /
Small Lymphocytic Lymphoma (SLL) and Prolymphocytic Leukemia (PLL).

II. To evaluate the safety and toxicity profile of carfilzomib in relapsed or refractory
chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL)/prolymphocytic leukemia
(PLL).

SECONDARY OBJECTIVES:

I. To evaluate efficacy of carfilzomib therapy in relapsed or refractory chronic lymphocytic
leukemia (CLL)/small lymphocytic leukemia (SLL)/prolymphocytic leukemia (PLL) to justify
future phase II studies.

II. To determine the degree and duration of cellular proteosome inhibition induced by
carfilzomib and relationship of this to pharmacodynamics, response and toxicity.

III. To determine the pharmacokinetics (plasma and cellular) of carfilzomib and relationship
of this to proteosome inhibition, pharmacodynamics, response, and toxicity.IV. To examine
the effect of carfilzomib on pharmacodynamic parameters including cytokines, changes in
downstream targets including NF-kappa B (p50/p65 binding; I-kappa B level, P-I-kappa B
level,select target genes), p53 (p53 nuclear levels, p53 nuclear binding, and select target
genes), ER stress proteins, and p73.

OUTLINE: This is a dose-escalation study of carfilzomib.Patients receiving carfilzomib
intra-venous(IV) over 30 minutes once daily, on days 1, 2, 8, 9, 15, and 16. Treatment
repeats every 28 days for up to 12 courses in the absence of disease progression or
unacceptable toxicity.


Inclusion Criteria:



- Previously treated patients with a diagnosis of chronic lymphocytic leukemia (CLL),
small lymphocytic lymphoma (SLL), or prolymphocytic leukemia (PLL) by NCI Criteria
with intermediate or high risk B-Cell chronic lymphocytic leukemia (CLL)(Modified Rai
stage) satisfying at least one of the criteria for active disease requiring
treatment;patients with a history of Richter's transformation are eligible if they
now have evidence of chronic lymphocytic leukemia (CLL) only, with < 10% large cells
in the bone marrow

- Massive or progressive splenomegaly and/or lymphadenopathy; or need for cytoreduction
for stem cell transplant

- Anemia (hemoglobin < 11 g/dl) or thrombocytopenia (platelets < 100 x 10^9/L)

- Presence of weight loss > 10% over the preceding 6 month period

- NCI grade 2 or 3 fatigue

- Fevers > 100.5 °C or night sweats for greater than 2 weeks without evidence of
infection

- Progressive lymphocytosis with an increase of > 50% over a 2 month period or an
anticipated doubling time of less than 6 months

- Creatinine Clearance (CrCl) > 15mL/min

- Alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)

- Bilirubin =< 2 times the upper limit of normal, unless disease related

- Platelets >= 20 x 10^9/L and absence of active bleeding

- Patients must have an ECOG performance status =< 2

- Patients must not have secondary cancers that result in a life expectancy of <2 years
or that would confound assessment of toxicity in this study

- Patients of all racial/ethnic groups are eligible for the study if they meet
eligibility criteria outlined-

- Patients must provide written informed consent

Exclusion Criteria:

- Absence of previously treated chronic lymphocytic leukemia (CLL)

- Female subject that is pregnant or breastfeeding; women of childbearing potential and
men must agree to use adequate contraception prior to study entry, duration of study
participation,and 30 days following study completion; should a woman become pregnant
or suspect she is pregnant while participating in this study, she should inform her
treating physician immediately;confirmation that the subject is not pregnant must be
established by a negative serum -human chorionic gonadotropin (beta-hCG) pregnancy
test result obtained during screening; pregnancy testing is not required for
post-menopausal or surgically sterilized women

- Patients with congestive heart failure (CHF)in whom pre-treatment hydration would be
prohibitive;New York Heart Association (NYHA) Class III/IV CHF is excluded

- Patients who have had treatment for chronic lymphocytic leukemia (CLL) within 2
weeks, although palliative steroids are acceptable

- Patient unable to give written informed consent

- Failure to recover from toxicity of previous radiotherapy or chemotherapy to grade 1

- Patients with active infections requiring intravenous (IV) antibiotic/antiviral
therapy are not eligible for entry onto the study until resolution of the infection;
patients on prophylactic antibiotics or antivirals are acceptable

- Patients who have previously taken bortezomib

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine safety of carfilzomib by evaluating the toxicity profile.

Outcome Description:

The safe use of carfilzomib will be assessed by: Determining the dose limiting toxicity and maximal tolerated dose of carfilzomib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) and prolymphocytic leukemia (PLL) To evaluating the toxicity profile of carfilzomib in relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) and prolymphocytic leukemia (PLL)

Outcome Time Frame:

Up to 24 months

Safety Issue:

Yes

Principal Investigator

Jennifer Woyach, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

OSU-09108

NCT ID:

NCT01212380

Start Date:

October 2010

Completion Date:

Related Keywords:

  • B-cell Chronic Lymphocytic Leukemia
  • Hematopoietic/Lymphoid Cancer
  • Prolymphocytic Leukemia
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Prolymphocytic Leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Prolymphocytic
  • Lymphoma

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210