Phase 1
N=8
Interleukin-15 (IL-5) in Combination With Avelumab (Bavencio) in Relapsed/Refractory Mature T-cell Malignancies
Peripheral T-cell Lymphoma NOS · Mycosis Fungoides · Sezary Syndrome · Anaplastic Large Cell Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT03905135 ↗Enrolled (actual)
8
Serious AEs
75.0%
Results posted
Sep 2022
Primary outcome: Primary: Maximum Tolerated Dose (MTD) of Interleukin 15 — NA; NA mcg/kg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- rhIL-15 (Drug); Avelumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Mar 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Interleukin 15 |
NA; NA | — |
| SECONDARY Mean Progression Free Survival (PFS) |
303; 61.5 | — |
| SECONDARY Mean Event-free Survival (EFS) |
176; 33.54 | — |
| SECONDARY Mean Overall Survival (OS) |
529; 300 | — |
| SECONDARY Overall Response in Participants With Greater Than or Equal to 50% Programmed Death-ligand 1 (PD-L1) Expressing Tumor Cells |
2; 0; 2; 2; 2; 0 | — |
| SECONDARY Number of Participants With Overall Best Response |
0; 0; 2; 0; 0; 0 | — |
| SECONDARY Mean Duration of Response (DOR) |
107; NA | — |
Summary
Background:
Some T-cell lymphomas and leukemias do not respond to standard treatment. Researchers hope to develop a treatment that works better than current treatments.
Objective:
To test if interleukin (IL-5) combined with avelumab is safe and effective for treating certain cancers.
Eligibility:
People ages 18 and older with relapsed T-cell leukemias and lymphomas for which no standard treatment exists or standard treatment has failed
Design:
Participants will be screened with:
* Medical history
* Physical exam
* Blood, urine, heart, and lung tests
* Possible tumor biopsy
* Bone marrow biopsy: A small needle will be inserted into the hipbone to take out a small amount of marrow.
* Computed tomography (CT) or positron emission tomography (PET) scans and magnetic resonance imaging (MRI): Participants will lie in a machine that takes pictures of the body.
Participants will get the study drugs for 6 cycles of 28 days each. They will have a midline catheter inserted: A tube will be inserted into a vein in the upper chest. They will get Interleukin-15 (IL-5) as a constant infusion over the first 5 days of every cycle. They will get avelumab on days 8 and 22 of each cycle. They will be hospitalized for the first week of the first cycle.
Participants will have tests throughout the study:
* Blood and urine tests
* Another tumor biopsy if their disease gets worse
* Scans every 8 weeks
* Possible repeat MRI
* Another bone marrow biopsy at the end of treatment, if there was lymphoma in the bone marrow before treatment, and they responded to treatment everywhere else.
After they finish treatment, participants will have visits every 60 days for the first 6 months. Then visits will be every 90 days for 2 years, and then every 6 months for 2 years. Visits will include blood tests and may include scans.
Eligibility Criteria
- INCLUSION CRITERIA:
- Patients must have histologically or cytologically proven relapsed/refractory T-cell lymphoma other than adult T-cell leukemia/lymphoma (ATLL), angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma T follicular helper phenotype (PTCL-TFH), or enteropathy-associated T-cell lymphoma (EATL), confirmed by the Laboratory of Pathology, National Cancer Institute (NCI)
- Patients with CD30 (also known as TNFRSF8) + mycosis fungoides/Sezary syndrome (MF/SS) or CD30+ anaplastic large cell lymphoma (ALCL) must have relapsed after or become intolerant to treatment with brentuximab vedotin.
- A formalin fixed tissue block or 15 slides of tumor sample (archival or fresh) must be available for performance of correlative studies. NOTE: Patients must be willing to have a tumor biopsy if prior tissue or adequate archival tissue is not available (i.e., post-enrollment and prior to treatment).
- Disease must be measurable with at least one measurable lesion by response evaluation criteria in lymphoma (RECIL) 2017 or Modified Severity-Weighted Assessment Tool (mSWAT) criteria or have an abnormal clonal T-cell population detectable by peripheral blood flow cytometry
- Age greater than or equal to 18 years
NOTE: Because no dosing or adverse event data are currently available on the use of rhIL-15 in combination with avelumab in patients 1, with the exception of the following: alopecia, sensory neuropathy grade less than or equal to 2, or other grade less than or equal to 2 not constituting a safety risk based on investigator's judgment
- Patients who are receiving any other investigational agents
- Patients who have had prior therapy with any antibody/drug targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) Tcell coregulatory proteins (immune checkpoints)
- Current use of immunosuppressive medication, EXCEPT for the following:
- Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
- Systemic corticosteroids at physiologic doses less than or equal to 10 mg/day of prednisone or equivalent; or,
- Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication)
- Patients with known central nervous system (CNS) involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with previous malignant disease other than the target malignancy within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
- Patients with history of any organ transplantation, including allogenic stem cell transplantation
- Received a live vaccine within 4 weeks of the first dose of avelumab. Vaccination with a live vaccine while on trial is prohibited. NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
- Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to recombinant human Interleukin-15 (rhIL-15) or avelumab
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, or psychiatric illness/social situations that would limit compliance with study requirements
- Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding. Based on its mechanism of action, avelumab can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. These potential risks may also a
Data sourced from ClinicalTrials.gov (NCT03905135). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.