Study of Ruxolitinib in Relapsed or Refractory T or NK Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT02974647
• Recruitment Status: Recruiting
• First Posted: November 28, 2016
• Last Update Posted: October 7, 2022
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Cornell University; Dana-Farber Cancer Institute; Thomas Jefferson University
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: November 23, 2016
• First Posted Date: November 28, 2016
• Last Update Posted Date: October 7, 2022
• Study Start Date: November 2016
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 25, 2016)

disease control rate [ Time Frame: 2 years ]

defined as the combination of complete response (CR), partial response (PR) and stable disease (SD). The reason we use this definition instead of the more conventional partial/complete response rate is twofold.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Ruxolitinib in Relapsed or Refractory T or NK Cell Lymphoma
• Official Title: Phase II Multicenter Study of Ruxolitinib in Relapsed or Refractory T or NK Cell Lymphoma
• Brief Summary: The purpose of this study is to test any good and bad effects of the study drug called ruxolitinib. Ruxolitinib works by blocking a protein called JAK. JAK works along with another protein called STAT and is important for survival of many T or NK-cell lymphomas. By blocking JAK, ruxolitinib may cause T or NK-cell lymphomas to shrink.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma
• Intervention: Drug: Ruxolitinib

Study Arms

• Experimental: rel/ref PTCLtumors are known to contain mutations associ
  Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Ruxolitinib should be taken by mouth every 12 hours approximately the same time each day (+/- 2 hours). Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.
  Intervention: Drug: Ruxolitinib
• Experimental: with rel/ref PTCL with functional evidence of JAK/STAT
  Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Ruxolitinib should be taken by mouth every 12 hours approximately the same time each day (+/- 2 hours). Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.
  Intervention: Drug: Ruxolitinib
• Experimental: with rel/ref PTCL who do not meet criteria for cohort 1 or 2.
  Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Ruxolitinib should be taken by mouth every 12 hours approximately the same time each day (+/- 2 hours).Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.
  Intervention: Drug: Ruxolitinib
• Experimental: Rare sub-type expansion cohort: T-PLL and T-LGL and non-MF CTCL with JAK fusion mutations.
  Patients will receive ruxolitinib 20mg BID orally on 28 day cycles. Treatment may continue until disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.
  Intervention: Drug: Ruxolitinib

• Publications *: Moskowitz AJ, Ghione P, Jacobsen E, Ruan J, Schatz JH, Noor S, Myskowski P, Vardhana S, Ganesan N, Hancock H, Davey T, Perez L, Ryu S, Santarosa A, Dowd J, Obadi O, Pomerantz L, Yi N, Sohail S, Galasso N, Neuman R, Liotta B, Blouin W, Baik J, Geyer MB, Noy A, Straus D, Kumar P, Dogan A, Hollmann T, Drill E, Rademaker J, Schoder H, Inghirami G, Weinstock DM, Horwitz SM. A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas. Blood. 2021 Dec 30;138(26):2828-2837. doi: 10.1182/blood.2021013379.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 29, 2021): 82
• Original Estimated Enrollment (submitted: November 25, 2016): 52
• Estimated Study Completion Date: November 2024
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Pathologically confirmed T or NK cell lymphoma at the enrolling institution. For CTCL, patients with stage IB disease or greater are eligible.
• Relapse or refractory disease after at least 1 systemic therapy except for T-PLL where untreated patients may be allowed after discussion with P.I.
• Age ≥ 18
• ECOG ≤ 2

• Measurable disease defined by:

  • Lugano Classification for systemic lymphoma or
  • Atypical and or malignant lymphocytes quantifiable by flow cytometry or morphology in blood or bone marrow or
  • mSWAT > 0 or Sezary count ≥ 1000 cells/μL for CTCL

• Previous systemic anti-cancer therapy for T-cell lymphoma must have been discontinued at least 2 weeks prior to treatment.

  • Glucocorticoids aimed at controlling lymphoma-related symptoms are allowed as long as they are tapered down to 20mg or less by the time of ruxolitiib initiation
  • Topical steroids for CTCL are permitted
  • See section 6.2 Subject Exclusion Criteria for guideline regarding adjuvant and maintenance therapy for prior malignancy

• Patients must meet the following lab criteria:

  • ANC ≥ 1.0/mm^3 or ANC >/= 0.5/mm^3 (if patient has baseline neutropenia due to lymphoma), platelets ≥ 100 x 10^9/L or ≥ 50 x 10^9/L (if related to lymphoma), Hgb ≥ 8g/dL
  • Patients with LGL or T-PLL are not required to meet a minimum ANC or hemoglobin value for eligibility
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or; ≤ 3 x ULN if documented hepatic involvement with lymphoma, or ≤ 5 x ULN if history of Gilbert's ; AST and ALT ≤ 3 x ULN; ≤ 5 x ULN if due to lymphoma involvement
  • Creatinine clearance ≥ 30 mL/min; creatinine clearance of 15-29 mL/min will be allowed as long as baseline platelets are ≥ 150 x 10^9/L
• For patients with positive hepatitis B core antibody or surface antigen, hepatitis B PCR must be negative and prophylaxis with entecavir or equivalent is required.
• Patients with HIV are allowed provided that they are on anti-retroviral treatment with no active infections.

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, clinically significant pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• ECOG performance status >2
• Prior therapy with ruxolitinib

• Receiving systemic 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
  • Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy (other than T-cell lymphoma) is permissible after discussion with the MSK principal Investigator

• Women of reproductive potential† must have a negative Serum ß human chorionic gonadotropin (ß-HCG) pregnancy test.

  • A female of reproductive potential is a sexually mature female 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Alison Moskowitz, MD; 212-639-4839

Contact: Steven Horwitz, MD; 212-639-3045

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02974647
• Other Study ID Numbers: 16-1542
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current

Collaborators

• Cornell University
• Dana-Farber Cancer Institute
• Thomas Jefferson University

Investigators

• Principal Investigator: Alison Moskowitz, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: October 2022