PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of itacitinib in combination with alemtuzumab in
patients with T-cell prolymphocytic leukemia (T-PLL).
SECONDARY OBJECTIVES:
I. To evaluate the event free survival (EFS) in patients (pts) with T-PLL treated with
itacitinib in combination with alemtuzumab.
II. To evaluate response complete remission (CR), complete remission without blood count
recovery (CRi), or partial remission (PR) (CR/CRi or PR) of itacitinib in combination with
alemtuzumab in patients with T-PLL.
III. To explore the single-agent activity of itacitinib in pts with T-PLL. IV. To assess the
time to response, response duration, and overall survival (OS) in pts with T-PLL treated with
the combination of itacitinib and alemtuzumab.
EXPLORATORY OBJECTIVES:
I. To explore the effect of itacitinib on STAT5 phosphorylation in pts with T-PLL II. To
explore the association of pretreatment somatic mutations and the dynamics of STAT5
phosphorylation with response.
OUTLINE: This is a dose-escalation study of alemtuzumab.
CYCLE 1: Patients receive itacitinib orally (PO) once daily (QD) on days 1-28 and alemtuzumab
intravenously (IV) over 2 hours on days 15, 17, 19, 21, 23, 25, and 27 in the absence of
disease progression of unacceptable toxicity.
CYCLE 2 AND BEYOND: Patients receive itacitinib PO QD on day 1-28 and alemtuzumab IV over 2
hours on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, and 27. Treatment repeats every
28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients who achieve a response (CR/CRi or PR) may receive itacitinib for up to
8 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Inclusion Criteria:
- Patients with a diagnosis of T-cell prolymphocytic leukemia (T-PLL) will be eligible
(both treatment naïve and relapsed patients are eligible).
- Age >/= 18 years.
- Patients must not have had chemotherapy or antibody therapy for 7 days prior to
starting ITACITINIB. However, patients with rapidly proliferative disease may receive
hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
- Adequate organ function as defined below: liver function (bilirubin </=2mg/dL, AST and
ALT </=3 x ULN or </=5 x ULN if related to leukemic involvement); kidney function
(estimated creatinine clearance > 50); known cardiac ejection fraction of > or = 45%
within the past 3 months; and platelet count </=30,000.
- ECOG performance status of </= 2.
- A negative urine pregnancy test is required within 1 week for all women of
childbearing potential prior to enrolling on this trial.
- Patient must have the ability to understand the requirements of the study and signed
informed consent. A signed informed consent by the patient or his legally authorized
representative is required prior to their enrollment on the protocol.
Exclusion Criteria:
- Patients with a diagnosis of T-cell prolymphocytic leukemia (T-PLL) will be eligible
(both treatment naïve and relapsed patients are eligible).
- Age >/= 18 years.
- Patients must not have had chemotherapy or antibody therapy for 7 days prior to
starting ITACITINIB. However, patients with rapidly proliferative disease may receive
hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
- Adequate organ function as defined below: liver function (bilirubin </=2mg/dL, AST and
ALT </=3 x ULN or </=5 x ULN if related to leukemic involvement); kidney function
(estimated creatinine clearance > 50); known cardiac ejection fraction of > or = 45%
within the past 3 months; and platelet count </=30,000.
- ECOG performance status of </= 2.
- A negative urine pregnancy test is required within 1 week for all women of
childbearing potential prior to enrolling on this trial.
- Patient must have the ability to understand the requirements of the study and signed
informed consent. A signed informed consent by the patient or his legally authorized
representative is required prior to their enrollment on the protocol.
