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Testing Ruxolitinib and Duvelisib for Lymphoma Treatment

Phase I Multicenter Study of Ruxolitinib and Duvelisib in Relapsed or Refractory T- or NK-Cell Lymphomas

Phase 1 Interventional Memorial Sloan Kettering Cancer Center · NCT05010005

This study is testing a combination of two medications, ruxolitinib and duvelisib, to see if they can help people with relapsed or hard-to-treat NK-cell or T-cell lymphomas feel better.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment70 (estimated)
Ages18 Years and up
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Drugs / interventionsbrentuximab, ruxolitinib, prednisone
Locations9 sites (Miami, Florida and 8 other locations)
Trial IDNCT05010005 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety of ruxolitinib, administered at a fixed dose, alongside duvelisib, which will be given at varying doses, in patients with relapsed or refractory NK-cell or T-cell lymphomas. The goal is to determine the effects of this combination therapy on these specific types of lymphoma. Participants must have pathologically confirmed mature T-cell lymphomas and have received prior treatments. The study is designed to gather data on the efficacy and safety of these medications in this patient population.

Who should consider this trial

Good fit: Ideal candidates include individuals with relapsed or refractory mature T-cell lymphomas who have undergone at least one prior therapy.

Not a fit: Patients with lymphomas that are not mature T-cell or NK-cell types may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat lymphomas.

How similar studies have performed: Other studies have shown promise with similar combination therapies in treating lymphomas, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

a) Pathologically-confirmed mature T-cell lymphomas at the enrolling institution.

Permitted histologies include (for dose escalation and expansion):

i) Stage ≥Ib CTCL, which has relapsed or progressed after at least two systemic therapies. In order to ensure balanced enrollment for patients with systemic T-cell lymphoma and CTCL, a maximum of 15 CTCL patients will be enrolled in expansion cohort.

ii) Systemic anaplastic large cell lymphoma that has relapsed after therapy containing brentuximab vedotin.

iii) T-cell prolymphocytic leukemia (treatment naïve permitted)

For the following histologies, patients are required to have received at least 1 prior therapy (dose escalation and expansion):

iv) T-cell large granular lymphocytic leukemia

v) Aggressive NK-cell leukemia

vi) Adult T-cell leukemia/lymphoma

vii) Extranodal NK/T- cell lymphoma, nasal type

viii) Enteropathy-associated T-cell lymphoma

ix) Monomorphic epitheliotropic intestinal t-cell lymphoma

x) Hepatosplenic T cell lymphoma

xi) Subcutaneous panniculitis-like T-cell lymphoma

xii) Primary cutaneous anaplastic large cell lymphoma

xiii) Primary cutaneous gamma/delta T-cell lymphoma

xiv) Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma

xv) Peripheral T-cell lymphoma, not otherwise specified

xvi) Angioimmunoblastic T cell lymphoma

xvii) Follicular T-cell lymphoma

xviii) Nodal peripheral T-cell lymphoma wih T follicular helper phenotype

b) Nodal periphal T-cell lymphoma wih T follicular helper phenotype Specific for T-PLL and TFH lymphoma expansion: histologies must be pathologically confirmed at the enrolling institutions i) T-cell prolymphocytic leukemia (treatment naïve permitted) ii) T-follicular helper lymphomas (must have received at least 1 prior treatment)

c) Age ≥18 years at time of enrollment

d) Performance status, as assessed in the ECOG grading system, ≤2

e) Laboratory criteria.

Laboratory criteria

i) For dose escalation phase:

1. Absolute neutrophil count ≥1.0 K/mcL (Note: growth factor is allowed)
2. Platelet count ≥80 K/μl or ≥50 K/μl if due to lymphoma
3. Creatinine ≤1.5 × ULN OR Measured calculated creatinine clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN

i. Creatinine clearance should be calculated per institutional standard

d. Direct bilirubin ≤1.5x upper limit of normal (ULN) or ≤3x ULN if documented hepatic involvement with lymphoma, or ≤5x ULN if history of Gilbert's syndrome; AST and ALT ≤ 3x ULN; or ≤ 5x ULN if due to lymphoma involvement

ii) For dose expansion phase and T-PLL/TFH lymphoma expansion:

1. Absolute neutrophil count ≥1.0 K/mcL or ≥0.5 K/mcL if due to lymphoma or ≥0.0 K/mcL if due to T-PLL or large granular lymphocytic leukemia (LGL) (Note: growth factor is allowed).
2. Platelet count ≥80 K/μl or ≥50 K/μl if due to lymphoma
3. c. Creatinine ≤1.5 × ULN OR Measured calculated creatinine clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN

i. Creatinine clearance should be calculated per institutional standard d. Direct bilirubin ≤1.5x upper limit of normal (ULN) or ≤3x ULN if documented hepatic involvement with lymphoma, or ≤5x ULN if history of Gilbert's syndrome; AST and ALT ≤ 3x ULN; or ≤ 5x ULN if due to lymphoma involvement

f) Measurable disease, defined by at least one of the following:

* Revised International Working Group Classification for systemic lymphoma19
* Atypical T lymphocytes quantifiable by flow cytometry or morphology in the peripheral blood or bone marrow
* mSWAT (Modified Severity Weighted Assessment Tool) \>0

  g) Ability to swallow pills

  h) Women of reproductive potential\* must have a negative serum or urine β human chorionic gonadotropin (βhCG) pregnancy test within 14 days of initiating therapy. All women of reproductive potential and all sexually active male patients must agree to use adequate methods of birth control (e.g. latex condoms) throughout the study and for 3 months after the last dose of study drug.
  * A woman of reproductive potential is a sexually-mature woman who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).
* The effects of duvelisib on conception, pregnancy, and lactation are unknown. Since duvelisib has not been evaluated in pregnant or nursing women, the treatment of pregnant women or women of childbearing potential who are not using a highly effective contraception is contraindicated.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant women. (Lactating women must agree not to breast feed while taking study medications).
3. Prior allogeneic stem cell transplant within 6 months of starting treatment or patients with active GVHD requiring immunosuppression.

a. Prior allogeneic stem cell transplant may be allowed after discussion with MSK PI if no GVHD or immunosuppression is present at time of enrollment...

d) Prior use of duvelisib or ruxolitinib if either agent was discontinued due to toxicity.

e) Previous systemic anti-cancer therapy for TCL within 14 days of initiating study drug

a. Patients who have received localized RT as part of their immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSK Principal Investigator.

i. Patients receiving treatment with single agent ruxolitinib or duvelisib may be allowed to enroll onto the study without a washout period

b. Systemic corticosteroids must be tapered to 20mg/day or less prednisone (or equivalent) upon start of investigational treatment.

c. Topical steroids for CTCL is permitted on study.

f) Ongoing use of immunosuppressant medications, including corticosteroids greater than 20mg of prednisone or equivalent at the time of enrollment

g) History of chronic liver disease, veno-occlusive disease, or current alcohol abuse

h) Administration of a live vaccine within 6 weeks of first dose of study drug.

i) Prior surgery or gastrointestinal condition that may adversely affect drug absorption (e.g., gastric bypass surgery, gastrectomy)

j) Patients with HIV infection if they meet either of the below criteria:

i. detectable viral load ii. undetectable viral load with CD4 count \<200 or not taking anti-retroviral medications.

k) Patients with chronic hepatitis B or C as defined by positive hepatitis B or C serology:

* Subjects with a negative HBsAg and a positive HBcAb require an undetectable/negative hepatitis B DNA test (e.g., polymerase chain reaction \[PCR\] test) to be enrolled, and must receive hepatitis B prophylaxis until at least 6 months after completion of study drug(s).

  l) Subjects with active CMV (defined as positive CMV PCR with clinical manifestations consistent with active CMV infection) and requiring therapy. Carriers will be monitored per institutional guidelines.

  m) Unable or unwilling to receive prophylaxis against pneumocystis, herpes simplex virus, or herpes zoster

  g) Use of medications or consumption of foods that are strong inducers or inhibitors of CYP3A
* Such agents must be discontinued at least 2 weeks prior to study intervention
* Patients who (after enrollment) require use of a strong CYP3A4 inhibitor to treat a fungal/mold infection will require dose reductions n) Receipt of treatment for tuberculosis within 2 years prior to enrollment

  o) Receiving therapy for another primary malignancy (other than T-cell lymphoma).
* Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator.
* Early-stage cutaneous basal cell and squamous cell carcinomas are permissible
* Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy is potentially permissible after discussion with the MSK Principal Investigator.

  p) Known central nervous system or meningeal involvement by TCL (in the absence of symptoms, investigation into central nervous system involvement is not required).

  q) Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition) or any important medical illness that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study.

Where this trial is running

Miami, Florida and 8 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions T-cell LymphomasNK-Cell LymphomasT-cell Prolymphocytic LeukemiaT-cell Large Granular Lymphocyte Leukemiamature T-cell lymphomasRuxolitinibDuvelisibRelapsed or Refractory
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.