Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers



Status:Recruiting
Conditions:Skin Cancer, Cancer, Infectious Disease, Lymphoma, Lymphoma
Therapuetic Areas:Immunology / Infectious Diseases, Oncology
Healthy:No
Age Range:18 - Any
Updated:4/4/2019
Start Date:September 18, 2017
End Date:January 1, 2020

Use our guide to learn which trials are right for you!

A Phase II Study of Talimogene Laherparepvec Followed by Talimogene Laherparepvec + Nivolumab in Refractory T Cell and NK Cell Lymphomas, Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma, and Other Rare Skin Tumors

This phase II trial studies how well talimogene laherparepvec works and nivolumab in treating
patients with lymphomas that do not responded to treatment or non-melanoma skin cancers that
have spread to other places in the body or do not responded to treatment. Biological
therapies, such as talimogene laherparepvec, use substances made from living organisms that
may stimulate or suppress the immune system in different ways and stop tumor cells from
growing. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's
immune system attack the cancer, and may interfere with the ability of tumor cells to grow
and spread. Giving talimogene laherparepvec and nivolumab may work better in treating
patients with lymphomas or non-melanoma skin cancers.

PRIMARY OBJECTIVES:

I. To determine the frequency of patients responding (response rate) to talimogene
laherparepvec monotherapy.

SECONDARY OBJECTIVES:

I. To determine the local response rate to talimogene laherparepvec in injected tumors.

II. To determine the response rate to talimogene laherparepvec + nivolumab (NIVO).

III. To identify potential pre-treatment and on-treatment correlative biomarkers of local and
systemic immune response.

OUTLINE:

Patients receive talimogene laherparepvec intratumorally (IT) on day 1. Patients without
response at week 12, may also receive nivolumab intravenously (IV) over 60 minutes on day 1.
Cycles repeat every 21 for course 1 then every 14 days for up to 1 year in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 3 years.

Inclusion Criteria:

- Patients must have histologic or cytologic diagnosis of non-melanoma skin cancer
(NMSC) or lymphomas other than B-cell lymphomas; as both of those terms are categories
rather than specific diagnoses, specific guidance on eligible tumor types is provided
below

- Included tumor types

- T cell and NK cell lymphomas, including, but not limited to: cutaneous T-cell
lymphomas (CTCL), mycosis fungoides (MF), Sezary syndrome (SS), peripheral T-cell
lymphoma (PTCL), ALK-positive and ALK-negative anaplastic large cell lymphoma
(ALCL), and NK-cell lymphomas

- Merkel cell carcinoma

- Squamous cell carcinoma of the skin, including keratoacanthomas, vulvar squamous
carcinoma, and mixed histology tumors, such as basosquamous carcinoma, and
squamous cell carcinoma of unknown primary consistent with skin origin

- Other non-melanoma skin cancers

- Basal cell carcinoma

- Malignant sweat gland tumors, including porocarcinoma, hidradenocarcinoma,
spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and
related entities, squamoid eccrine ductal carcinoma, cutaneous adenoid
cystic carcinoma, digital papillary adenocarcinoma, primary cutaneous
mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma, primary
cutaneous signet ring cell carcinoma, cutaneous apocrine gland carcinoma,
and extraocular sebaceous carcinoma

- Adnexal carcinoma

- Trichilemmal carcinoma

- Extramammary Paget's disease

- Any other rare tumor of the skin with approval of principle investigator
(PI)

- Patients with T cell and natural killer (NK) cell lymphomas must be refractory to, be
intolerant of, have relapsed following, or have refused all standard life-prolonging
therapies

- Patients with non-melanoma skin cancers (NMSC) must have advanced or refractory tumors

- Advanced/unresectable is defined by at least 1 of the following criteria: tumors
2 cm or more, tumors considered unresectable, tumors invading deep tissues such
as muscle, cartilage or bone, tumors showing perineural invasion, and/or tumors
metastatic to loco-regional lymph nodes and/or distant sites

- Refractory is defined by persistent or recurrent tumor despite prior therapy
consisting of at least 1 of the following: surgery, radiation therapy,
intralesional therapy, topical therapy, or systemic therapy

- Subjects must have at least 1 cutaneous, subcutaneous, or nodal lesion that is
suitable for intralesional injection, with or without the use of ultrasound; lesions
in mucosal surfaces (periocular, nasal, etc) are not eligible for injection because
the area cannot be properly contained with an occlusive dressing

- Subjects must have radiographically or clinically measurable disease, defined as at
least one lesion that is >= 10 mm in diameter in at least 1 dimension, or an aggregate
of lesions that measures >= 10 mm in diameter in at least 1 dimension

- Subjects must be able and willing to undergo serial biopsies of injected lesion(s)
and, when applicable and clinically feasible, non-injected lesions

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Absolute neutrophil count (ANC) >= 1.2 x 10^9/L

- Hemoglobin >= 9 g/dL without transfusion in the preceding 7 days

- Platelets >= 75 x 10^9/L

- Serum total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (patients
with Gilbert's syndrome with a total bilirubin < 3.0 mg/dL)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x
institutional ULN

- Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault
formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min

- Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin
time (PTT) =< 1.5 x institutional ULN, unless the subject is on anticoagulant therapy;
(if the subject is receiving anticoagulant therapy, PT, and activated PTT (aPTT) must
be within therapeutic range of intended use of anticoagulants)

- Women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence from
heterosexual intercourse) prior to study entry, during the study participation, and
for 7 months after the last dose of the drug; WOCBP must have a negative serum
pregnancy test within 14 days prior to randomization; should a woman become pregnant
or suspect she is pregnant while she or her partner is participating in this study,
she should inform her treating physician immediately; men must agree to use adequate
contraception prior to study entry, during the study participation and for 7 months
after the last dose of the drug

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Excluded tumor types

- Melanoma

- Bone sarcomas

- Soft tissue sarcomas, including angiosarcoma, primary cutaneous leiomyosarcoma,
dermatofibrosarcoma protuberans

- Leukemias

- Myeloid sarcoma, leukemia cutis, and chloroma

- Hodgkin's lymphoma

- B cell lymphoma

- Patients who have had systemic therapy or radiotherapy within 3 weeks prior to the
first dose of study therapy

- Untreated central nervous system (CNS) involvement

- Previous treatment with talimogene laherparepvec or other herpes virus based therapy;
(prior therapy with checkpoint inhibitors and/or other immunotherapy is allowed)

- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1 excepting alopecia, peripheral sensory
neuropathy, and stable endocrine insufficiencies such as thyroid and adrenal
insufficiency)

- Second primary malignancy, only if it would affect the safety of the treatment or the
subject's ability to complete study-related procedures

- History or evidence of active autoimmune disease (e.g., pneumonitis,
glomerulonephritis, vasculitis, or other); or history of active autoimmune disease
that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive
drugs or biological agents used for treatment of autoimmune diseases) within 2 months
of enrollment; (replacement therapy [e.g., thyroxine for hypothyroidism, insulin for
diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency] is not considered a form of systemic treatment for autoimmune disease)

- Evidence of clinically significant immunosuppression such as the following:

- Primary immunodeficiency state such as severe combined immunodeficiency disease

- Receiving systemic immunosuppressive therapy including prednisone > 10 mg per day
(or equivalent), tacrolimus, everolimus, sirolimus, mycophenolate mofetil,
etanercept, infliximab, etc.

- Recipients of solid organ, bone marrow, or stem cell transplants; auto transplant
recipients are allowed

- Notes: Oral steroid doses =< 10 mg/day of prednisone (or equivalent) are not
considered immunosuppressive and are permitted; inhaled and intraarticular
corticosteroids are permitted

- Active herpetic skin lesions or prior complications of herpetic infection (e.g.,
herpetic keratitis or encephalitis)

- Viral infections requiring intermittent or chronic systemic (intravenous or oral)
treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical
use

- Other viral infections:

- Known to have acute or chronic active hepatitis B or hepatitis C infection

- Known to have human immunodeficiency virus (HIV) infection

- Prior therapy with viral-based tumor vaccine

- Received live vaccine within 28 days prior to enrollment

- Subject who is unwilling to minimize exposure with his/her blood or other body fluids
to individuals who are at higher risks for human herpesvirus 1 (HSV-1) induced
complications such as immunosuppressed individuals, individuals known to have HIV
infection, pregnant women, or children under the age of 1 year, during talimogene
laherparepvec treatment and through 30 days after the last dose of talimogene
laherparepvec

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Female subject is pregnant or breast-feeding, or planning to become pregnant during
study treatment and through 7 months after the last dose of treatment; female subject
of childbearing potential who is unwilling to use acceptable method(s) of effective
contraception during study treatment and through 7 months after the last dose of
treatment; sexually active subjects and their partners unwilling to use male or female
latex condom to avoid potential viral transmission during sexual contact while on
treatment and within 30 days after treatment with talimogene laherparepvec

- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to
talimogene laherparepvec or any of its components or nivolumab, or history of severe
hypersensitivity reaction to any monoclonal antibody
We found this trial at
21
sites
Chapel Hill, North Carolina 27599
Principal Investigator: Frances A. Collichio
Phone: 877-668-0683
?
mi
from
Chapel Hill, NC
Click here to add this to my saved trials
666 Elm Street
Buffalo, New York 14263
(716) 845-2300
Principal Investigator: Igor Puzanov
Phone: 800-767-9355
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
?
mi
from
Buffalo, NY
Click here to add this to my saved trials
12605 East 16th Avenue
Aurora, Colorado 80045
720-848-0000
Principal Investigator: Theresa M. Medina
Phone: 720-848-0650
University of Colorado Hospital, Site Top medical professionals, superior medicine and progressive change make University...
?
mi
from
Aurora, CO
Click here to add this to my saved trials
401 North Broadway
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Richard F. Ambinder
Phone: 410-955-8804
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
55 Fruit St
Boston, Massachusetts 02114
(617) 724-4000
Principal Investigator: Nicole R. LeBoeuf
Phone: 877-726-5130
Massachusetts General Hospital Cancer Center An integral part of one of the world
?
mi
from
Boston, MA
Click here to add this to my saved trials
450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Nicole R. LeBoeuf
Phone: 877-442-3324
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
?
mi
from
Boston, MA
Click here to add this to my saved trials
303 East Superior Street
Chicago, Illinois 60611
Principal Investigator: Sunandana Chandra
Phone: 312-695-1301
?
mi
from
Chicago, IL
Click here to add this to my saved trials
10 Barnes West Drive
Creve Coeur, Missouri 63141
Principal Investigator: George Ansstas
Phone: 800-600-3606
?
mi
from
Creve Coeur, MO
Click here to add this to my saved trials
Fairway, Kansas 66205
Principal Investigator: Benjamin C. Powers
Phone: 913-945-7552
?
mi
from
Fairway, KS
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Martha P. Mims
Phone: 713-798-1354
?
mi
from
Houston, TX
Click here to add this to my saved trials
1 Medical Center Dr
Lebanon, New Hampshire 03756
 (603) 650-5000
Principal Investigator: Keisuke Shirai
Phone: 800-639-6918
Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock is a national leader in patient-centered health care and building...
?
mi
from
Lebanon, NH
Click here to add this to my saved trials
1983 Marengo St
Los Angeles, California 90033
(323) 226-2622
Principal Investigator: Gino K. In
Phone: 323-865-0451
Los Angeles County-USC Medical Center The origins of LAC+USC Medical Center date back to 1878,...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
1441 Eastlake Ave
Los Angeles, California 90033
(323) 865-3000
Principal Investigator: Gino K. In
Phone: 323-865-0451
U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
New Brunswick, New Jersey 08903
Principal Investigator: Janice M. Mehnert
Phone: 732-235-8675
?
mi
from
New Brunswick, NJ
Click here to add this to my saved trials
Emile St
Omaha, Nebraska 68198
(402) 559-4000
Principal Investigator: Alissa S. Marr
Phone: 402-559-6941
Univ of Nebraska Med Ctr A vital enterprise in the nation’s heartland, the University of...
?
mi
from
Omaha, NE
Click here to add this to my saved trials
Pittsburgh, Pennsylvania 15232
Principal Investigator: Melissa A. Burgess
Phone: 412-647-8073
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
Sacramento, California 95817
Principal Investigator: Joseph M. Tuscano
Phone: 916-734-3089
?
mi
from
Sacramento, CA
Click here to add this to my saved trials
Saint Louis, Missouri 63129
Principal Investigator: George Ansstas
Phone: 800-600-3606
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials
660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: George Ansstas
Phone: 800-600-3606
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials
150 Entranceway Drive
Saint Peters, Missouri 63376
Principal Investigator: George Ansstas
Phone: 800-600-3606
?
mi
from
Saint Peters, MO
Click here to add this to my saved trials
2000 Circle of Hope Dr
Salt Lake City, Utah 84112
(801) 585-0303
Principal Investigator: John R. Hyngstrom
Phone: 888-424-2100
Huntsman Cancer Institute at University of Utah Huntsman Cancer Institute (HCI) is part of the...
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials