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Phase 1b/2 Study of Dinaciclib (SCH 727965) and Ofatumumab in Relapsed and Refractory CLL/SLL/B-PLL

Phase 1/Phase 2
18 Years
Open (Enrolling)
B-cell Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia

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Trial Information

Phase 1b/2 Study of Dinaciclib (SCH 727965) and Ofatumumab in Relapsed and Refractory CLL/SLL/B-PLL


I. To determine the tolerable dose of combination therapy with ofatumumab and dinaciclib
(phase 1b component) in chronic lymphocytic leukemia (CLL), small lymphocytic leukemia
(SLL), and B-cell prolymphocytic leukemia (B-PLL).

II. To characterize the toxicity of combination therapy with ofatumumab and dinaciclib in

III. To determine the overall response rate associated with this treatment as assessed by
consensus response criteria. (Phase II)


I. To estimate progression-free survival (PFS) after combination treatment with ofatumumab
and dinaciclib.

II. To characterize the pharmacokinetics of dinaciclib when given in combination with

III. To correlate pharmacokinetic features of dinaciclib with response, toxicity
(particularly tumor lysis syndrome), and pharmacodynamic endpoints.

IV. To perform detailed baseline and serial pharmacodynamic studies of combination therapy
with ofatumumab and dinaciclib and correlate these with response to therapy.

V. To correlate baseline disease-risk parameters (i.e., ZAP-70 expression, interphase
cytogenetics, IgVH mutational analysis, and other clinical prognostic factors) with response
to therapy. (Exploratory)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and
on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2
hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment
repeats every 28 days for up to 7 courses in the absence of disease progression or
unacceptable toxicity.

Plasma, serum, urine, and buccal swab samples are collected at baseline and periodically
during study for pharmacokinetic, pharmacogenomic, and pharmacodynamic studies, and other
biomarker studies.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for up to 5 years.

Inclusion Criteria:

- Patients must have histologically confirmed B-cell chronic lymphocytic leukemia
(B-CLL)/small lymphocytic lymphoma (SLL) or a B-cell prolymphocytic leukemia (B-PLL)
according to 2008 World Health Organization (WHO) diagnostic criteria

- Patients must meet one or more of the following modified indications for treatment as
described in the 2008 International Workshop on chronic lymphocytic leukemia (CLL)
(IWCLL) guidelines for the diagnosis and treatment of CLL:

- Progressive disease or marked splenomegaly and/or lymphadenopathy or disease
requiring de-bulking for future allogeneic transplantation

- Anemia (hemoglobin < 11 mg/dL) or thrombocytopenia (platelets < 100,000/μL)

- Unexplained weight loss exceeding 10% of body weight over the preceding 6 months

- Cancer Therapy Evaluation Program (CTEP) Active Version of the Common
Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 fatigue

- Fevers > 100.5 º F or night sweats for greater than 2 weeks without evidence of

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

- Need for cytoreduction prior to allogeneic stem cell transplant

- Patients with known brain metastases should be excluded from this clinical trial

- Patients previously treated with ofatumumab will be eligible as long as their disease
responded to previous treatment (defined as achieving at least stable disease by
consensus criteria) and did not subsequently progress < 3 months from completing

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥ 1,000/μL in absence of bone marrow involvement

- Platelets ≥ 30,000/μL in absence of bone marrow involvement

- Total bilirubin ≤ 5 times institutional upper limit of normal (ULN) unless secondary
to Gilbert syndrome

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase[SGPT]) ≤
2.5 times institutional ULN unless due to infiltration of the liver

- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min

- Organ and marrow function; documented by bone marrow pathology obtained within 6
months of beginning protocol treatment if no intervening therapy for CLL/SLL/B-PLL

- Patients with a history of current/previous infection with hepatitis B virus will be
eligible if receiving appropriate antiviral prophylaxis

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation

- Pregnant and/or breast-feeding women are excluded from this study

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition as dinaciclib

- No history of anaphylactic reaction to rituximab or other anti-CD20 monoclonal

- Patients with glucose-6-phosphate dehydrogenase(G6PD) deficiency are excluded

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- No prior malignancy, except for adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, or other cancer from which the subject is considered
by his or her physician to have a 2-year survival expectation

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with

- Patients must have received at least one prior therapy that includes either
fludarabine or equivalent nucleoside analogue, or an alternative regimen if there was
a contraindication (i.e., autoimmune hemolytic anemia) or patient elected not to
receive fludarabine

- No patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Corticosteroids alone will not be considered prior therapy, but must be
discontinued at least 24 hours prior to the first day of therapy unless
continued for indications other than the primary malignancy

- No patients who are receiving any other investigational agent

- Patients who have received prior treatment with dinaciclib will not be eligible

Type of Study:


Study Design:

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

Outcome Measure:

Maximum-tolerated dose graded according to the National Cancer Institute (NCI ) CTCAE v4.0 (Phase I)

Outcome Description:

Assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.

Outcome Time Frame:

Up to day 56

Safety Issue:


Principal Investigator

Jeffrey Jones

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

January 2012

Completion Date:

Related Keywords:

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



Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Columbus, Ohio  43210-1240