Patients must have histologically confirmed a diagnosis T-PLL that is relapsed or refractory after prior treatment.

Age ≥ 18 years.

• Patients must not have had T-PLL directed chemotherapy or antibody therapy for 7 days prior to starting ruxolitinib. However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

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 ≥ 45% within the past 3 months prior to enrolling on the trial;
• Platelet count of ≥ 30,000 (unless determined to be due to disease involvement).

ECOG performance status of ≤ 2.

For patients with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

Patients with a history of HCV infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.

The effects of ruxolutinib on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, 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. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• History of bilateral tubal ligation or another surgical sterilization procedure.

Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), IUD, Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ruxolitinib and venetoclax administration.

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.