Clinical Trials /

Nivolumab With Standard of Care Chemotherapy for Peripheral T Cell Lymphomas

NCT03586999

Description:

This regimen aims to become the first line treatment for peripheral T cell lymphoma, using nivolumab with the standard of care chemotherapy.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma
  • Hepatosplenic T-Cell Lymphoma
  • Nodal Peripheral T-Cell Lymphoma with TFH Phenotype
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • Primary Cutaneous Gamma-Delta T-Cell Lymphoma
  • Subcutaneous Panniculitis-Like T-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab With Standard of Care Chemotherapy for Peripheral T Cell Lymphomas
  • Official Title: Nivolumab With Standard of Care Chemotherapy for the First Line Treatment of Peripheral T Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 18-0708.cc
  • NCT ID: NCT03586999

Conditions

  • Peripheral T Cell Lymphoma

Interventions

DrugSynonymsArms
Nivolumab and EPOCHNivolumab and EPOCH

Purpose

This regimen aims to become the first line treatment for peripheral T cell lymphoma, using nivolumab with the standard of care chemotherapy.

Detailed Description

      Patients in this study will receive nivolumab in combination with the standard of care
      dose-adjusted EPOCH (etoposide, prednisone, vincristine, doxorubicin, cyclophosphamide) for
      six 21 day cycles. Patients will then have an autologous stem cell transplant or continue to
      receive maintenance therapy with nivolumab.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and EPOCHExperimentalPatients will all receive nivolumab in combination with standard dose adjusted EPOCH for a planned 6 cycles, unless treatment is stopped early for disease progression or toxicity. Patients that have already received up to 1 cycle of standard of care chemotherapy will receive 5 cycles of experimental nivolumab + DA-EPOCH (dose adjusted, continuous infusion etoposide, prednisone, vincristine, doxorubicin, and bolus dosing of cyclophosphamide) for a total of 6 cycles of chemotherapy.
  • Nivolumab and EPOCH

Eligibility Criteria

        Inclusion Criteria:

        In order to be eligible to participate in this study, an individual must meet all of the
        following criteria:

          1. Ability to sign and date the consent form.

          2. Stated willingness to comply with all study procedures and be available for the
             duration of the study.

          3. Be a male or female aged > or = 18.

          4. Histologically confirmed new diagnosis of Stage II, III or IV Peripheral T-cell
             Non-Hodgkin's lymphoma not otherwise specified (NOS), Anaplastic large cell lymphoma
             (ALK negative) (ALK positive if IPI 3, 4, or 5), Angioimmunoblastic T-cell lymphoma,
             Enteropathy associated T-cell lymphoma (MEITL and EATL), Hepatosplenic T-cell
             lymphoma, gamma/delta T-cell lymphoma, subcutaneous panniculitis like T-cell lymphoma,
             and Nodal T-cell lymphomas with T-follicular helper phenotype.

          5. Available pathology material (fine needle aspirate is inadequate) for review at
             University of Colorado

          6. No prior therapy with the exception of prior radiation therapy and/or 1 cycle of
             chemotherapy (may be any chemotherapy regimen or even prednisone alone) based on
             current diagnosis and clinical condition. If given cytotoxic chemotherapy (one cycle
             only, e.g. CHOP), this cycle of treatment will count toward the 6 cycles of treatment
             given in the study.

          7. ECOG performance status 0 - 2.

          8. Laboratory status as follows:

               -  ANC > 1000 cells/mm3, unless cytopenias due to lymphoma (i.e., bone marrow
                  involvement or splenomegaly)

               -  Platelet Count > 100,000 /μL, or > 50,000 /μL if bone marrow involvement or
                  splenomegaly

               -  Total bilirubin ≤1.5 x upper normal limit, or ≤ 3 x upper normal limit if
                  documented hepatic involvement with lymphoma, or ≤ 5 x upper normal limit if
                  history of Gilbert's Disease.

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper
                  normal limit (≤ 5 x upper normal limit if documented hepatic involvement with
                  lymphoma).

               -  Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45
                  mL/min (Cockcroft-Gault, Appendix)

               -  PT or INR, and PTT ≤ 1.5 x upper limit of normal unless patient is receiving
                  anticoagulants. If patient is on warfarin therapy, levels should be within
                  therapeutic range.

          9. Patients with measurable disease. Measurable disease is defined as having at least one
             objective measurable disease parameter. A clearly defined, bi-dimensionally measurable
             defect or mass measuring at least 1.5 cm in diameter on the CT portion of a PET/CT or
             CT scan or MRI (if appropriate) will constitute measurable disease. Proof of lymphoma
             in the liver is required by a confirmation biopsy unless there is measurable disease
             by imaging. Skin lesions can be used as measurable disease provided bi-dimensional
             measurements are possible. Patients with non-measurable but evaluable disease may be
             eligible after discussion with the PI. Abnormal PET/CT scans will not constitute
             evaluable disease, unless verified by the CT scan portion, CT scan, or other
             appropriate imaging.

         10. For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use of contraceptive methods that result in a failure
             rate of < 1% per year during the treatment period and for at least 180 days after the
             last study treatment. 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). 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 postovulation methods) and withdrawal are not acceptable
             methods of contraception.

         11. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures 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 180 days
             after the last dose of study 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
             postovulation methods) and withdrawal are not acceptable methods of contraception.

         12. Patient must be able to adhere to the study visit schedule and other protocol
             requirements.

        Exclusion Criteria:

        An individual who meets any of the following criteria will be excluded from participation
        in this study:

          1. An additional malignancy treated with palliative intent within the past 2 years.
             Malignancies in patients who have completed definitive treatment with curative intent
             >1 year will be permitted after discussion with the PI. Adequately treated basal cell,
             squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or
             breast; prostate cancer of Gleason Grade 6 or less with stable PSA levels are allowed.

          2. Patients with a diagnosis of other PTCL histologies other than those specified in the
             inclusion criteria.

          3. Primary T-cell CNS lymphoma; however, secondary CNS disease is not an exclusion
             criteria.

          4. Pregnant or breastfeeding females.

          5. Contraindication to any of the required concomitant drugs or supportive treatments.

          6. Any other clinically significant medical disease or condition laboratory abnormality
             or psychiatric illness that, in the investigator's opinion, may interfere with
             protocol adherence or a subject's ability to give informed consent.

          7. Ejection fraction of <45% by either MUGA or ECHO.

          8. Has immunodeficiency or is being treated with immuno-suppressive therapy (aside from
             medications used to treat lymphoma) within 7 days of first dose of study treatment.
             Inhaled or topical steroids are accepted. Prednisone used to treat adrenal
             insufficiency in the absence of auto-immune disease is also acceptable.

          9. Auto-immune condition requiring immuno-suppressive disease modifying therapy within
             the prior 2 years. Replacement therapy, e.g. levothyroxine for thyroiditis or insulin
             for diabetes are acceptable.

         10. History of non-infectious pneumonitis requiring immuno-suppressive therapy.

         11. Active hepatitis B or C (with measurable virus or antigen in serum) or HIV. Patients
             who are seropositive because of hepatitis B virus vaccine or have a history of
             hepatitis B (with no measurable virus or antigen in serum) are eligible.

         12. Prior PD-1 or PD-L1 antibody treatment.

         13. Has received a live virus vaccine in 30 days preceding start of therapy.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:Start of study to end of study, for up to four years
Safety Issue:
Description:Toxicity analysis of nivolumab will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 and relationship to study drug or the amount of grade 4-5 non-hematologic toxicities.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Start of study to end of study, for up to four years
Safety Issue:
Description:PFS will be descriptive in nature (no formal statistical analyses will be conducted).
Measure:Correlative Analysis: Determine immune-related predictors of response to nivolumab plus EPOCH chemotherapy
Time Frame:Start of study to end of study, for up to four years
Safety Issue:
Description:This will be descriptive in nature (no formal statistical analyses will be conducted).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • Nivolumab
  • First Line Treatment
  • EPOCH
  • Standard of Care

Last Updated

November 7, 2019