Nivolumab With Standard of Care Chemotherapy for Peripheral T Cell Lymphomas

NCT03586999 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 18-0708.cc
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Peripheral T Cell Lymphoma

Keywords

Nivolumab; First Line Treatment; EPOCH; Standard of Care

Outcome Measures

Primary Outcomes (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.

  up to 100 days post transplant

Secondary Outcomes (5)

• Number of Participants With Adverse Events

  up to 100 days after last dose of nivolumab

• Efficacy: Overall Response Rate

  up to 100 days post transplant

• Efficacy: Progression Free Survival Rate

  up to 2 years after completion of treatment

• Efficacy: Event Free Survival

  up to 2 years after completion of treatment

• Immune-related Predictors of Response

  Within 6 months of treatment

Study Arms (1)

Nivolumab and EPOCH

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: Etoposide; Drug: Prednisolone; Drug: Oncovin; Drug: Cyclophosphamide; Drug: Hydroxydaunorubicin

Interventions

Nivolumab DRUG

Nivolumab injection is to be administered as an IV infusion.

Also known as: Opdivo

Nivolumab and EPOCH

Etoposide DRUG

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.

Also known as: Vepesid, Toposar

Nivolumab and EPOCH

Prednisolone DRUG

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.

Also known as: Oraped, PediaPred, Millipred

Nivolumab and EPOCH

Oncovin DRUG

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.

Also known as: Vincristine, Leurocristine

Nivolumab and EPOCH

Cyclophosphamide DRUG

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.

Also known as: cytophosphane

Nivolumab and EPOCH

Hydroxydaunorubicin DRUG

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.

Also known as: Adriamycin

Nivolumab and EPOCH

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• Pregnant or breastfeeding females.
• Contraindication to any of the required concomitant drugs or supportive treatments.
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (6)

• 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.

  PMID: 20660290 BACKGROUND

• 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.

  PMID: 18626005 BACKGROUND

• 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.

  PMID: 25006130 BACKGROUND

• 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.

  PMID: 28971899 BACKGROUND

• 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.

  PMID: 26518748 BACKGROUND

• 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.

  PMID: 34389271 BACKGROUND

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

Nivolumab; Etoposide; Prednisolone; prednisolone phosphate; Methylprednisolone; Vincristine; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides

Results Point of Contact

• Title: Brad Haverkos, MD
• Organization: University of Colorado

brad.haverkos@cuanschutz.edu

7208488698

Study Officials

• Brad Haverkos, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: July 16, 2018
• Study Start: November 7, 2018
• Primary Completion: May 26, 2021
• Study Completion: September 20, 2022
• Last Updated: October 29, 2024
• Results First Posted: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)