Ruxolitinib in Combination With Chemotherapy for Untreated Nodal T-Follicular Helper (TFH) Cell Lymphomas
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.
• 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
• Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale (PS) at time of enrollment. Patients with a performance status of 2 on the ECOG scale due to lymphoma may be eligible with principal investigator (PI) approval
• Histologically confirmed nodal T-follicular helper (TFH) cell lymphomas. Nodal TFH cell lymphomas include encompasses three subtypes:
‣ Angioimmunoblastic T-cell lymphoma (AITL)(World Health Organization \[WHO\]4R)/follicular helper T-cell lymphoma (TFH lymphoma), angioimmunoblastic type (ICC)/nodal TFH cell lymphoma, angioimmunoblastic-type (WHO5)
⁃ Nodal peripheral T-cell lymphoma (PTCL) with TFH phenotype (nodal PTCL, TFH)(WHO4R)/TFH lymphoma, NOS (ICC)/nodal TFH cell lymphoma, not otherwise specified (NOS) (WHO5)
⁃ Follicular T-cell lymphoma (FTCL)(WHO4R)/TFH lymphoma, follicular type (ICC)/ nodal TFH cell lymphoma, follicular-type (WHO5)
• Must be planned to receive full course (6 cycles) chemoimmunotherapy as per clinical standard of care for untreated nodal TFH cell lymphoma
• Have measurable disease, including at least 1 nodal site measuring 1.5 cm or 1 extranodal site measuring 1.0 cm in longest dimension on CT or FDG-PET or marrow-only disease (disease only found on bone marrow biopsy)
• Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
• Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm\^3 (≥ 50,000/mm\^3 in cases of marrow infiltration by lymphoma or hypersplenism per investigator assessment)
• Measured or calculated creatinine clearance ≥ 60 mL/min (glomerular filtration rate \[GFR\] can also be used in place of creatinine clearance \[CrCl\])
‣ Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN)
‣ (Patients with documented liver or pancreatic involvement with lymphoma may be enrolled if total bilirubin ≤ 3.0 x ULN. Patients with documented Gilbert disease may be enrolled if total bilirubin ≤ 5.0 x ULN) OR direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x ULN OR ≤ 5 x ULN for patients with liver involvement
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN
‣ Note: unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants, or patient is shown to have an antiphospholipid antibody on workup
• Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
‣ Note: unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants, or patient is shown to have an antiphospholipid antibody on workup
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of ≤ 1% per year during the treatment period and for at least 4 months after the last dose of study treatment. Women must refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a postmenopausal state (≤ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. Examples of contraceptive methods with a failure rate of ≤ 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception
• For women of childbearing potential, a negative serum pregnancy test result during screening period. Women who are considered not to be of childbearing potential are not required to have a pregnancy test
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last treatment. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure. Male patients considering preservation of fertility should bank sperm before study treatment
• TO BE ASSESSED UPON COMPLETION OF PART A FOR CONSIDERATION FOR PART B ONLY: Completion of first-line multi-agent chemotherapy with ruxolitinib with CHOP
• TO BE ASSESSED UPON COMPLETION OF PART A FOR CONSIDERATION FOR PART B ONLY: Documentation of response (PR or CR) per Lugano criteria within the previous 3 months
• TO BE ASSESSED UPON COMPLETION OF PART A FOR CONSIDERATION FOR PART B ONLY: Ineligible for or decline consolidative autologous stem cell transplantation. Ineligibility is defined by:
‣ Patient deemed ineligible for high-dose chemotherapy and ASCT based on physician's assessment
⁃ AND at least one of the following criteria:
• Age ≥ 65 years or
∙ Age ≥ 18 years and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score ≥ 3
• TO BE ASSESSED UPON COMPLETION OF PART A FOR CONSIDERATION FOR PART B ONLY: Recovery to ≤ grade 1 or baseline for any toxicities due to prior treatments, with the exception of peripheral neuropathy (recovery to ≤ grade 2) or alopecia