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Nivolumab With Standard of Care Chemotherapy for Peripheral T Cell Lymphomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03586999
Recruitment Status : Recruiting
First Posted : July 16, 2018
Last Update Posted : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE June 29, 2018
First Posted Date  ICMJE July 16, 2018
Last Update Posted Date November 8, 2019
Actual Study Start Date  ICMJE November 7, 2018
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2018)
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Start of study to end of study, for up to four years ]
    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.
  • Efficacy: Overall Response Rate [ Time Frame: Start of study to end of study, for up to four years ]
    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.
  • Efficacy: Complete Response Rate [ Time Frame: Start of study to end of study, for up to four years ]
    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.
  • Efficacy: Partial Response Rate [ Time Frame: Start of study to end of study, for up to four years ]
    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.
  • Efficacy: Rate of Stable Disease [ Time Frame: Start of study to end of study, for up to four years ]
    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.
  • Efficacy: Rate of Progressive Disease [ Time Frame: Start of study to end of study, for up to four years ]
    Efficacy will be measured according to 2017 RECIL criteria. Responses will be assessed by the investigator and will be based on PET/CT scan to be obtained after 6 cycles of induction chemotherapy.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03586999 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2018)
  • Progression Free Survival (PFS) [ Time Frame: Start of study to end of study, for up to four years ]
    PFS will be descriptive in nature (no formal statistical analyses will be conducted).
  • 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 ]
    This will be descriptive in nature (no formal statistical analyses will be conducted).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab With Standard of Care Chemotherapy for Peripheral T Cell Lymphomas
Official Title  ICMJE Nivolumab With Standard of Care Chemotherapy for the First Line Treatment of Peripheral T Cell Lymphoma
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Peripheral T Cell Lymphoma
Intervention  ICMJE Drug: Nivolumab and EPOCH
Nivolumab injection is to be administered as an IV infusion. DA-EPOCH dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using Mosteller formula and administered through IV. Dose adjustments at the beginning of each cycle do not need to be made unless there has been a >10% weight gain or loss. Patients receive six 21 day cycles of the medications.
Study Arms  ICMJE Experimental: Nivolumab and EPOCH
Patients 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.
Intervention: Drug: Nivolumab and EPOCH
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 12, 2018)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Brad Haverkos 720-848-0414 bradley.haverkos@ucdenver.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03586999
Other Study ID Numbers  ICMJE 18-0708.cc
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Brad Haverkos, MD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP