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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02974647

Collaborator

Cornell University (Other), Dana-Farber Cancer Institute (Other), Thomas Jefferson University (Other)

Enrollment

Locations

Arms

Duration (Months)

10.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Ruxolitinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

82 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Multicenter Study of Ruxolitinib in Patients With T or NK Cell Lymphoma That Has Either Come Back or Not Responded to Treatment

Study Start Date :

Nov 1, 2016

Anticipated Primary Completion Date :

Nov 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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.	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.	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.	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.	Drug: Ruxolitinib

Outcome Measures

Primary Outcome Measures

disease control rate [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States
2	Northwestern Medicine (Data collection and specimen analysis)	Chicago	Illinois	United States	60611
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
5	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
6	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
8	Weill Cornell Medical College	New York	New York	United States