Ignite Creation Date:
2025-12-24 @ 10:43 PM
Ignite Modification Date:
2026-01-02 @ 11:26 PM
Study NCT ID:
NCT03905135
Status:
COMPLETED
Last Update Posted:
2022-09-13
First Post:
2019-04-03
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Interleukin-15 (IL-5) in Combination With Avelumab (Bavencio) in Relapsed/Refractory Mature T-cell Malignancies
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 1 Study of Interleukin-15 in Combination With Avelumab (Bavencio) in Relapsed/Refractory Mature T-cell Malignancies
Status:
COMPLETED
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Detailed Description:
Background:
Mature T-cell cancers are a phenotypically heterogeneous group of malignancies which constitute 10-15% of all non-Hodgkin lymphomas (NHL). Patients with relapsed/refractory T cell lymphomas have limited therapeutic options, making new therapeutic approaches extremely important.
The immunologic effects of recombinant human Interleukin-15 (rhIL-15), a stimulatory cytokine that promotes the differentiation and activation of NK cells, monocytes and long-term cluster of differentiation 8 (CD8) + memory T-cells, has been assessed in several Phase 1 trials in cancer patients.
Avelumab is an anti-programmed death ligand-1 (PD-L1) fully human immunoglobulin G1 (IgG1) antibody that inhibits programmed cell death protein 1 (PD1)/PD-L1 interactions while leaving the PD1/programmed cell death ligand 2 (PD-L2) pathway intact and enhances immune activation against tumor cells. It has received United States (U.S.) Food and Drug Administration (FDA) accelerated approval for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma.
Unlike other approved anti-PD-L1/PD1 antibodies, avelumab induces lysis of tumor cells via antibody-dependent cell-mediated cytotoxicity (ADCC), indicating an additional mechanism of action. However, avelumab has not shown ADCC against normal immune cell subsets in humans.
A significant number of T-cell malignancies express PD-L1, and since the anti-PD-L1 antibody avelumab has shown ADCC activity in vitro, agents that may enhance ADCC by increasing number and activity of Fc-binding effector cells such as rhIL15 could improve efficacy of avelumab in these diseases.
Objectives:
To determine the safety and toxicity profile and the maximum tolerated dose (MTD) of continuous intravenous infusion (civ) recombinant human interleukin-15 (rhIL-15) administration in combination with standard intravenous (IV) avelumab treatment
Eligibility:
Age \>= 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of \<= 1
Histologically or cytologically confirmed relapsed and/or 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) and enteropathy-associated T-cell lymphoma (EATL).
Adequate organ and marrow function
Design:
Open-label, single-center, non-randomized Phase 1 study
Standard 3 + 3 design will be used to determine the MTD of dose-escalated rhIL-15 with fixed dose avelumab with a small expansion cohort at the MTD
Maximum 6 cycles (28-day cycle) of combination therapy
To explore all dose levels, including further evaluation in a dose expansion cohort, the accrual ceiling will be set at 30 patients.
Mature T-cell cancers are a phenotypically heterogeneous group of malignancies which constitute 10-15% of all non-Hodgkin lymphomas (NHL). Patients with relapsed/refractory T cell lymphomas have limited therapeutic options, making new therapeutic approaches extremely important.
The immunologic effects of recombinant human Interleukin-15 (rhIL-15), a stimulatory cytokine that promotes the differentiation and activation of NK cells, monocytes and long-term cluster of differentiation 8 (CD8) + memory T-cells, has been assessed in several Phase 1 trials in cancer patients.
Avelumab is an anti-programmed death ligand-1 (PD-L1) fully human immunoglobulin G1 (IgG1) antibody that inhibits programmed cell death protein 1 (PD1)/PD-L1 interactions while leaving the PD1/programmed cell death ligand 2 (PD-L2) pathway intact and enhances immune activation against tumor cells. It has received United States (U.S.) Food and Drug Administration (FDA) accelerated approval for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma.
Unlike other approved anti-PD-L1/PD1 antibodies, avelumab induces lysis of tumor cells via antibody-dependent cell-mediated cytotoxicity (ADCC), indicating an additional mechanism of action. However, avelumab has not shown ADCC against normal immune cell subsets in humans.
A significant number of T-cell malignancies express PD-L1, and since the anti-PD-L1 antibody avelumab has shown ADCC activity in vitro, agents that may enhance ADCC by increasing number and activity of Fc-binding effector cells such as rhIL15 could improve efficacy of avelumab in these diseases.
Objectives:
To determine the safety and toxicity profile and the maximum tolerated dose (MTD) of continuous intravenous infusion (civ) recombinant human interleukin-15 (rhIL-15) administration in combination with standard intravenous (IV) avelumab treatment
Eligibility:
Age \>= 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of \<= 1
Histologically or cytologically confirmed relapsed and/or 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) and enteropathy-associated T-cell lymphoma (EATL).
Adequate organ and marrow function
Design:
Open-label, single-center, non-randomized Phase 1 study
Standard 3 + 3 design will be used to determine the MTD of dose-escalated rhIL-15 with fixed dose avelumab with a small expansion cohort at the MTD
Maximum 6 cycles (28-day cycle) of combination therapy
To explore all dose levels, including further evaluation in a dose expansion cohort, the accrual ceiling will be set at 30 patients.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 19-C-0076 | None | None | View |