Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

PRIMARY OBJECTIVES:

I. To assess the safety of in vivo in host drug sensitivity testing in patients with breast
cancer and patients with lymphoma (nodal, extranodal or cutaneous lesions).

SECONDARY OBJECTIVES:

I. To assess the feasibility of in vivo in host drug sensitivity testing in this patient
population.

II. To identify targeted therapies with potential activity in relapsed lymphoma and
metastatic breast cancer.

III. To evaluate the adverse event profile within each patient population.

TERTIARY OBJECTIVES:

I. To assess for apoptosis in response to intratumoral injection using known biomarkers
(e.g., by morphology, Ki-67, caspace-3 assay as a marker of early apoptosis).

II. To evaluate intratumoral biomarkers, intratumoral cell populations, and distribution,
identify potential biomarkers that correlate with response to therapy based on individual
therapies.

OUTLINE:

Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive
up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat,
carfilzomib, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab
intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal
disease undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days,
patients with cutaneous disease undergo restaging FDG-PET, photography, and biopsy.

After completion of study treatment, patients are followed up at 3 months.

Inclusion Criteria:

- Histologically proven within the last 6 months of relapsed or refractory

- Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) nodal or extranodal OR

- Cutaneous T-cell lymphoma (CTCL) including mycosis fungoides (MF), as well as
transformed MF OR

- Breast adenocarcinoma with nodal or cutaneous metastases (stage 4)

- NOTE: Patients must be refractory to or intolerant of existing therapy(ies)
known to provide clinical benefit for their condition

- NOTE: The patient must not be a candidate for any curative therapy or any
known life-prolonging therapy

- Presence of lesions that are amenable for injections as determined by interventional
radiology

- NOTE: Nodal or extranodal sites must be palpable and easily accessible; sites
such as mediastinum, retroperitoneum, within solid organs, spinal sites, central
nervous system (CNS) sites, etc., are NOT allowed

- Measurable disease:

- For nodal or extranodal disease (lymphoma or breast): must have at least 2
lesions that are >= 20 mm (2.0 cm) in the longest diameter by physical exam
and/or on cross-sectional imaging and measurable in two perpendicular dimensions
per computed tomography PET-computed tomography (CT), that are amenable to
intralesional injections as determined by interventional radiology (including
tumors that can be safely accessed using imaging guidance and treated with
minimal risk to adjacent structures)

- For cutaneous lesions (lymphoma or breast): at least two visible, non-infected
skin lesions that are greater than 1 cm and are amenable to intralesional
injection

- Candidate for further therapy and able to wait 7 days prior to start of next systemic
therapy

- Absolute neutrophil count (ANC) >= 1000/mm^3 obtained =< 14 days prior to registration

- Platelet count >= 50,000/mm^3 obtained =< 14 days prior to registration

- International normalized ratio (INR)/prothrombin time (PT) =< 1.5 obtained =< 14 days
prior to registration

- Negative serum or urine pregnancy test done =< 7 days prior to registration, for
persons of childbearing potential only

- Provide written informed consent

- Willing to return to enrolling institution for follow-up

- Willing to provide tissue samples for correlative research purposes

Exclusion Criteria:

- Any of the following:

- Pregnant persons

- Nursing persons

- Persons of childbearing potential who are unwilling to employ adequate
contraception

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Systemic corticosteroids between pre-PET and post-PET evaluation and biopsy

- Prohibited treatments and or therapies

- Autologous stem cell transplant (ASCT) =< 12 weeks prior to registration

- Prior chemotherapy =< 2 weeks prior to registration

- Prior treatment with nitrosureas =< 4 weeks prior to registration

- Therapeutic anticancer antibodies =< 2 weeks prior to registration

- Radio- or toxin immunoconjugates =< 4 weeks prior to registration

- Radiation therapy to the injected area =< 2 weeks prior to registration

- Major surgery =< 2 weeks prior to registration

- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm

- Requires anticoagulation that cannot be discontinued prior to biopsy

- Note: Exception if able to hold antiplatelet agents 7 days prior to the
injections and biopsy

- NOTE: Low molecular weight heparin (LMWH) will be allowed for bridging if on
warfarin

- NOTE: Heparin for line patency without detectable lab abnormalities for
coagulation will be allowed