This phase I trial tests the safety, side effects and best dose of ruxolitinib in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy and how well the combination works in treating patients with untreated nodal T-follicular helper (TFH) cell lymphoma. Ruxolitinib phosphate blocks a protein called janus kinase, which may help keep abnormal blood cells or cancer cells from growing. It may also lower the body's immune response. Ruxolitinib phosphate is a type of tyrosine kinase inhibitor. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Doxorubicin is a type of anthracycline antitumor antibiotic. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving ruxolitinib in combination with CHOP chemotherapy may be safe, tolerable, and/or effective in treating patients with untreated nodal TFH cell lymphoma.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Ability to understand and willingness to sign a written informed consent document
Documented informed consent of the participant and/or legally authorized representative.
Assent, when appropriate, will be obtained per institutional guidelines
Be ≥ 18 years of age on day of signing informed consent
Disqualifiers
Contraindication to any of the individual components of CHOP, or if receiving an additional 6 cycles of anthracycline would place patient over the anthracycline lifetime cumulative dose (450 mg/m²)
Up to 30 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening, including prior to finalization of staging (not included as part of pre-phase treatment). If glucocorticoid treatment is urgently required at higher doses for lymphoma symptom control prior to the start of study treatment, tumor assessments must be completed prior to initiation of > 30-100 mg/day of prednisone or equivalent. Prednisone > 30-100 mg/day or equivalent may be given for a maximum of 7 days as a pre-phase treatment. If patients exceed the allowed dosing of corticosteroids, patients may still be eligible for the study provided that baseline imaging is performed (or repeated) after completion of the course of higher dose of steroids. Allowed corticosteroid dosing resets from the point of imaging forward and patients who do not exceed the allowed corticosteroid dosing from the point of imaging until initiation of study treatment may enroll
Prior organ transplantation
Known history of cirrhosis
Trial design
Design model
Single group
Treatments tested in this trial
Biospecimen Collection
Procedure/Surgery
Undergo blood sample collection
Bone Marrow Aspiration
Procedure/Surgery
Undergo bone marrow biopsy and aspiration
Bone Marrow Biopsy
Procedure/Surgery
Undergo bone marrow biopsy and aspiration
Computed Tomography
Procedure/Surgery
Undergo CT and FDG-PET/CT
Cyclophosphamide
Drug
Given IV
Doxorubicin
Drug
Given IV
Echocardiography Test
Procedure/Surgery
Undergo ECHO
FDG-Positron Emission Tomography
Procedure/Surgery
Undergo FDG-PET/CT
Filgrastim
Biological/Vaccine
Given SC
Fludeoxyglucose F-18
Other intervention
Given FDG
Multigated Acquisition Scan
Procedure/Surgery
Undergo MUGA
Pegfilgrastim
Biological/Vaccine
Given SC
Prednisone
Drug
Given PO
Questionnaire Administration
Other intervention
Ancillary studies
Ruxolitinib Phosphate
Drug
Given PO
Vincristine
Drug
Given IV
Treatment groups
20 Participants
are divided into 1 treatment group
Group A: Treatment (ruxolitinib, CHOP)Experimental treatment 16 interventions
Trial outcomes
Primary outcomes
1
Maximum tolerated dose (MTD) of ruxolitinib when given in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy
Will be defined as the highest dose of ruxolitinib tested in which fewer than 33% of patients experience a dose-limiting toxicity and at least 6 patients have been treated at that dose. The MTD will be the recommended phase 2 dose, provided that other safety considerations are acceptable.
Time frame
Prior to cycle 2 day 1 (cycle length = 21 days)
2
Incidence of adverse events
Will be evaluated using Common Terminology Criteria for Adverse Events version 5.0.
Time frame
Up to 30 days after last dose of treatment
Secondary outcomes
1
Rate of ruxolitinib discontinuation due to toxicity while receiving ruxolitinib with CHOP therapy (Part A)
Time frame
Up to 5 years
2
Complete response (CR) rate (Part A)
A simple binary proportion and corresponding 95% confidence interval will be used to estimate CR.
Time frame
Up to 5 years
3
Overall response rate (Part A)
A simple binary proportion and corresponding 95% confidence interval will be used to estimate overall response.
Time frame
Up to 5 years
4
Patient-reported outcomes (Part A)
Will be measured by the Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health and Functional Assessment of Chronic Illness Therapy (FACT)-Item GP5 scale. Will be reported descriptively.
Time frame
Up to 30 days after last dose of study treatment
Other outcomes
Sponsors and contacts
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