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Peripheral T Cell LymphomaPhase 1/2NCT03586999

Nivolumab With Standard of Care Chemotherapy for Peripheral T Cell Lymphomas

A Phase 1/2 study testing Nivolumab, Etoposide and Prednisolone in people with Peripheral T Cell Lymphoma, run by University of Colorado, Denver at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Peripheral T Cell Lymphoma
What is being tested?
Nivolumab, Etoposide and Prednisolone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
3 sitesUnited States
Study dates
7 Nov 2018to 20 Sep 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible to participate in this study, an individual must meet all of the following criteria:
  • Ability to sign and date the consent form.
  • Stated willingness to comply with all study procedures and be available for the duration of the study.
  • Be a male or female aged 18-80.
  • 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, y/8 T-cell lymphoma, Subcutaneous panniculitis-like T-cell lymphoma, and Nodal T-cell lymphomas with T-follicular helper phenotype.
  • Available pathology material (fine needle aspirate is inadequate) for review at the University of Colorado.
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  • 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.
  • ECOG performance status 0 - 2.
  • 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.
  • 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.
  • 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.
  • Patient must be able to adhere to the study visit schedule and other protocol requirements.

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • 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.
  • Patients with a diagnosis of other PTCL histologies other than those specified in the inclusion criteria.
  • Primary T-cell CNS lymphoma; however, secondary CNS disease is not an exclusion criteria.
  • Pregnant or breastfeeding females.
  • Contraindication to any of the required concomitant drugs or supportive treatments.
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  • 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.
  • Ejection fraction of <45% by either MUGA or ECHO.
  • 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.
  • 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.
  • History of non-infectious pneumonitis requiring immuno-suppressive therapy.
  • 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.
  • Prior PD-1 or PD-L1 antibody treatment.
  • Has received a live virus vaccine in 30 days preceding start of therapy.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • City of Hope Cancer Center

    Duarte, California, 91010

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Nivolumab With Standard of Care Chemotherapy for the First Line Treatment of Peripheral T Cell Lymphoma

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

Read the 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.

Keywords
Nivolumab, First Line Treatment, EPOCH, Standard of Care
Medical subject headings
Lymphoma, T-Cell, Peripheral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo

    Nivolumab injection is to be administered as an IV infusion.

  • EtoposideDrug

    Also called Vepesid, Toposar

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the 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.

  • PrednisoloneDrug

    Also called Oraped, PediaPred, Millipred

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the 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.

  • OncovinDrug

    Also called Vincristine, Leurocristine

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the 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.

  • CyclophosphamideDrug

    Also called cytophosphane

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the 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.

  • HydroxydaunorubicinDrug

    Also called Adriamycin

    Dosage calculations will be based on the patient's body surface area (BSA) at baseline, recommend using the 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 groups in NCT03586999
Study groupRoleWhat they receive
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.
Receives: Drug: Nivolumab; Drug: Etoposide; Drug: Prednisolone; Drug: Oncovin; Drug: Cyclophosphamide; Drug: Hydroxydaunorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy: Complete Response Rate

    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.

    Measured: up to 100 days post transplant

Secondary outcomes (5)

  1. Number of Participants With Adverse Events

    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.

    Measured: up to 100 days after last dose of nivolumab

  2. Efficacy: Overall Response Rate

    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. Complete response (CR), complete disappearance of all target lesions and Deauville score 1-3. Partial response (PR), ≥30% decrease in the sum of longest diameters of target lesions but not a CR and Deauville score 4-5. Stable disease (SD), <30% decrease or ≤ 20% increase in the sum of longest diameters of target lesions. Progressive disease (PD), >20% increase in the sum of longest diameters of target lesions, For small lymph nodes measuring < 15 mm post-therapy, a minimum of 5 mm increase in longest diameter to > 15 mm, or new lesions.

    Measured: up to 100 days post transplant

  3. Efficacy: Progression Free Survival Rate

    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.

    Measured: up to 2 years after completion of treatment

  4. Efficacy: Event Free Survival

    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. Events defined as start of new treatment, progression, or death.

    Measured: up to 2 years after completion of treatment

  5. Immune-related Predictors of Response

    We assessed PD-L1 expression using immunohistochemistry on pre-treatment tumor tissue. The outcome of measurement was complete response yes vs. no. Using logistic regression, we assessed if the percentage of PDL1+ cells was predictive of achieving a complete response.

    Measured: Within 6 months of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2018
  2. Study start7 Nov 2018
  3. Primary completion26 May 2021
  4. Study completion20 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03586999
Sponsor's protocol ID
18-0708.cc
Status last verified
Oct 2024
First submitted
29 Jun 2018
Last updated
29 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schmitz N, Trumper L, Ziepert M, Nickelsen M, Ho AD, Metzner B, Peter N, Loeffler M, Rosenwald A, Pfreundschuh M. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood. 2010 Nov 4;116(18):3418-25. doi: 10.1182/blood-2010-02-270785. Epub 2010 Jul 21.

    PubMed 20660290

  • Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008 Sep 1;26(25):4124-30. doi: 10.1200/JCO.2008.16.4558. Epub 2008 Jul 14.

    PubMed 18626005

  • Ellin F, Landstrom J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014 Sep 4;124(10):1570-7. doi: 10.1182/blood-2014-04-573089. Epub 2014 Jul 8.

    PubMed 25006130

  • Maeda Y, Nishimori H, Yoshida I, Hiramatsu Y, Uno M, Masaki Y, Sunami K, Masunari T, Nawa Y, Yamane H, Gomyo H, Takahashi T, Yano T, Matsuo K, Ohshima K, Nakamura S, Yoshino T, Tanimoto M. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017 Dec;102(12):2097-2103. doi: 10.3324/haematol.2017.167742. Epub 2017 Sep 29.

    PubMed 28971899

  • Dunleavy K, Pittaluga S, Shovlin M, Roschewski M, Lai C, Steinberg SM, Jaffe ES, Wilson WH. Phase II trial of dose-adjusted EPOCH in untreated systemic anaplastic large cell lymphoma. Haematologica. 2016 Jan;101(1):e27-9. doi: 10.3324/haematol.2015.131151. Epub 2015 Oct 30. No abstract available.

    PubMed 26518748

  • Ghafouri S, Fenerty K, Schiller G, de Vos S, Eradat H, Timmerman J, Larson S, Mead M. Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience. Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12):861-872. doi: 10.1016/j.clml.2021.07.002. Epub 2021 Jul 19.

    PubMed 34389271

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab, Etoposide and Prednisolone in people with Peripheral T Cell Lymphoma, run by University of Colorado, Denver at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy: Complete Response Rate (time frame: up to 100 days post transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03586999, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2024.

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