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Interleukin-15 (IL-5) in Combination With Avelumab (Bavencio) in Relapsed/Refractory Mature T-cell Malignancies

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ClinicalTrials.gov Identifier: NCT03905135
Recruitment Status : Recruiting
First Posted : April 5, 2019
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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.
  • CT or PET scans and 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 IL-15 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.

...


Condition or disease Intervention/treatment Phase
Peripheral T-cell Lymphoma-not Otherwise Specified Mycosis Fungoides Sezary Syndrome ALK-negative Anaplastic Large Cell Lymphoma Drug: rhIL-15 Biological: Avelumab Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Interleukin-15 in Combination With Avelumab (Bavencio) in Relapsed/Refractory Mature T-cell Malignancies.
Actual Study Start Date : June 7, 2019
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2026


Arm Intervention/treatment
Experimental: 1- Experimental Treatment: Dose Escalation
IL-15 by civ infusion at escalating doses of 1, 2, 3 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with avelumab by IV infusion at a dose of 10mg/kg on Day 8 and 22 of each cycle, to determine MTD
Drug: rhIL-15
IL-15 will be administered by continuous intravenous infusion in a dose-escalation fashion with a starting dose of 1 mcg/kg/day, a second dose level of 2 mcg/kg/day, a third dose level at 3 mcg/kg/day, and a fourth dose level at 4 mcg/kg/day on days 1-5 of each of six cycles.

Biological: Avelumab
Avelumab (IV over 1 hour) will be administered at a dose of 10 mg/kg on days 8 and 22 of each of six cycles.

Experimental: 2- Experimental Treatment: Dose Expansion
IL-15 by civ infusion at the MTD on days 1- 5 of cycles 1-6 with avelumab at 10mg/kg on Day 8 and 22 ofeach cycle
Drug: rhIL-15
IL-15 will be administered by continuous intravenous infusion in a dose-escalation fashion with a starting dose of 1 mcg/kg/day, a second dose level of 2 mcg/kg/day, a third dose level at 3 mcg/kg/day, and a fourth dose level at 4 mcg/kg/day on days 1-5 of each of six cycles.

Biological: Avelumab
Avelumab (IV over 1 hour) will be administered at a dose of 10 mg/kg on days 8 and 22 of each of six cycles.




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: 28 days ]
    Frequency (number and percentage) of treatment-emergent adverse events



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients must have one of the following histologically or cytologically proven relapsed and/or refractory T-cell malignancies: confirmed by the Laboratory of Pathology, NCI, as follows: peripheral T-cell lymphoma NOS, mycosis fungoides/S(SqrRoot)(Copyright)zary syndrome, or ALK-negative anaplastic large cell lymphoma, for which no standard therapy exists or standard therapy has failed
  • Patients with CD30+ MF/SS or CD30+ ALK-negative 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 RECIL 2017 or 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 <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

  • ECOG performance status less than or equal to 1
  • Adequate organ and marrow function as defined:

    • Absolute neutrophil count greater than 1,000/mcL
    • Absolute lymphocyte count greater than or equal to 500/mcL
    • Hemoglobin greater than or equal to 9 g/dL
    • Leukocytes greater than or equal to 3,000/mcL
    • Platelets greater than 100,000/mcL
    • Total bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN)
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional ULN
    • Serum creatinine less than or equal to 1.5 X institutional ULN OR
    • Creatinine clearance greater than or equal to 50 mL/min/1.73 m2 for patients with creatinine levels greater than 1.5 institutional ULN
  • Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP)

NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. WOCBP must have a negative pregnancy test (HCG blood or urine) during screening.

  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of rhIL-15 and avelumab administration. 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.
  • Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document

EXCLUSION CRITERIA:

  • Patients with other T-cell leukemias/lymphomas not specified in the inclusion criteria
  • Chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)
  • Persisting toxicity related to prior therapy of grade > 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 PD-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 10 mg/day of prednisone or equivalent; or,
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Patients with known 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 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 apply to other agents used in this study
  • Patients with active bacterial infections, documented HIV infection or positive screening serology, PCR evidence for active or chronic hepatitis B or hepatitis C, or positive screening HBV/HCV serology without documentation of successful curative treatment
  • Patients with active or history of any autoimmune disease, including asthma requiring chronic inhaled or oral corticosteroids, or with history of asthma requiring mechanical ventilation; patients with a history of mild asthma that are on or can be switched to non-corticosteroid bronchodilator regimens are eligible
  • Patients with active or history of any autoimmune disease
  • Cardiovascular disease: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (greater than or equal to New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
  • Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905135


Contacts
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Contact: Maureen E Edgerly, R.N. (240) 760-6013 edgerlym@pbmac.nci.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Milos Miljkovic, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03905135     History of Changes
Other Study ID Numbers: 190076
19-C-0076
First Posted: April 5, 2019    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 3, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
T-cell Lymphoproliferative Disorder
Cutaneous T Cell Lymphoma
Anti-PD-L1 monoclonal antibody
Antibody Dependent Cellular Cytotoxicity
Additional relevant MeSH terms:
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Mycoses
Lymphoma
Lymphoma, T-Cell
Mycosis Fungoides
Sezary Syndrome
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs