This phase Ib trial studies the side effects and best dose of alemtuzumab when given together with itacitinib in treating patients with T-cell prolymphocytic leukemia. Itacitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with alemtuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving itacitinib and alemtuzumab may work better in treating patients with T-cell prolymphocytic leukemia compared to standard of care treatment.

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 \