A Phase 1 Study of the Clinical and Immunologic Effects o... | NCT01946789

NCT01946789

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
U01CA154967	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
N-803 IV 0.3/0.5 ug/kg	Experimental	Biological: ALT-803
N-803 IV 1.0 ug/kg	Experimental	Biological: ALT-803
N-803 IV 3.0 ug/kg	Experimental	Biological: ALT-803
N-803 IV 6.0 ug/kg	Experimental	Biological: ALT-803
N-803 Subcutaneous 6.0 ug/kg	Experimental	Biological: ALT-803
N-803 Subcutaneous 10.0 ug/kg	Experimental	Biological: ALT-803
N-803 Subcutaneous 15.0 ug/kg	Experimental	Biological: ALT-803
N-803 Subcutaneous 20.0 ug/kg

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ALT-803	Biological	N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.

Measure	Description	Time Frame
Dose Limiting Toxicity	The safety endpoint is the MTD of ALT-803, defined as the dose level below that at which ≥2 of 6 patients experience a DLT.	9 months

Measure	Description	Time Frame
Number of Participants Who Developed Anti-drug Antibodies to ALT-803	Immunogenicity of ALT-803 assessed by ELISA	14 days post final dose, up to 135 days
To Evaluate the Effect of Escalating Doses of ALT-803: Pharmacokinetics (Half Life and Tmax)

Eligibility Module

Eligibility Criteria

ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

Histological or cytological confirmed malignancy in the following disease groups: melanoma that is metastatic or unresectable, non-small cell lung carcinoma, renal cell carcinoma or squamous cell head and neck carcinoma, for which standard curative or palliative measures do not exist or are no longer effective.
Primary site may be cutaneous or unknown, but mucosal and ocular primaries are excluded.
Patients with non-small lung cancer must have had prior EGFR and ALK testing. Patients with sensitizing mutations in EGFR or ALK rearrangements should have been treated with prior targeted agents and have had progression or discontinued due to toxicity from these agents.
No patients with known brain metastases.

PRIOR/CONCURRENT THERAPY:

At least one prior therapy using an agent with the potential for prolonged remission.
Patients with BRAF v600 mutation should be excluded or may be included after experiencing progression following treatment with BRAF inhibitor regimen or if they consent to forgo FDA-approved therapies that increase median survival.
At least 4 weeks from last dose of prior chemotherapy or immunomodulator therapy with full recovery of acute toxicities. For patients coming off molecularly-targeted therapy, at least 2 weeks since last dose and recovery from laboratory and constitutional toxicities.
At least 2 weeks from completion of prior radiation therapy with full recovery from toxicities.
At least 4 weeks from last dose of prior investigational therapy with recovery to meet baseline eligibility criteria.
Not receiving any current anticancer therapy
No patients who have had chemotherapy, targeted therapy, or radiotherapy and have not recovered from acute toxicity to their pretreatment baseline or to a grade 1 level within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. For resolution of autoimmune toxicity from prior immune therapy, patients must be off steroids for at least 30 days without relapse of autoimmune toxicity, or it must be at least 30 days from their last dose of infliximab or related immunosuppressive therapy without relapse of autoimmune toxicity.
No patients who are receiving any other investigational agents.
No patients who are receiving chronic systemic or regular inhaled corticosteroid use within 7 days prior to initiation of protocol therapy.
No immunosuppressive therapy within 30 days prior to treatment start.

PATIENT CHARACTERISTICS

Age >18 years
Both men and women of all races and ethnic groups are eligible.

Performance Status

ECOG performance status ≤1
Life expectancy of greater than 6 months.

Bone Marrow Function

leukocytes ≥3,000/mcL
absolute lymphocyte count ≥500/mcL
absolute neutrophil count ≥1,000/mcL (without hematopoietic growth factors)
platelets ≥100,000/mcL (without transfusion)
hemoglobin ≥ 10 gm/dL (may be transfused but must be stable without clinical evidence of ongoing blood loss or hemolysis)

Hepatic Function

total bilirubin within normal institutional limits
AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

Kidney Function

Creatinine within normal institutional limits OR
Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Pulmonary Function

• No history of severe COPD or emphysema or interstitial lung disease currently on home supplemental oxygen. Patients with NSCLC with stable COPD or emphysema not requiring supplemental oxygen are eligible.

Cardiac Function

No symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia. Patients who have underlying risk factors for cardiac disease should be excluded or undergo clearance stress-based cardiac function testing. The pre-treatment QTc must be <500 msec.
No class II or greater congestive heart failure as described in the New York Heart Association Functional Classification criteria or serious arrhythmias likely to increase the risk of cardiac complications of cytokine therapy.

Other

Women of child-bearing potential and men must agree to use adequate contraception.
Ability to understand and the willingness to sign a written informed consent document.
No uncontrolled inter-current illness or psychiatric illness/social situations that would limit compliance with study requirements.
No pregnant women.
No HIV-positive patients.
No positive hepatitis C serology or active hepatitis B infection.
No active bacterial or fungal infection.
No inability to home monitor blood pressure.
Patients with thyroid disease should be excluded unless euthyroid on suppressive or replacement therapy.

Name	Affiliation	Role
Marc Ernstoff, MD	Roswell Park Cancer Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Minnesota		Minneapolis	Minnesota	55455	United States
Dartmouth Hitchcock Medical Center

Label	URL
Related Info	View source

Arm/Group Information

ID	Title	Description
FG000	N-803 IV 0.3/0.5 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG001	N-803 IV 1.0 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG002	N-803 IV 3.0 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG003	N-803 IV 6.0 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG004	N-803 Subcutaneous 6.0 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG005	N-803 Subcutaneous 10.0 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG006	N-803 Subcutaneous 15.0 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG007	N-803 Subcutaneous 20.0 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.
FG008	N-803 Intratumoral 10.0 ug/kg Followed by N-803 15.0 ug/kg Subcutaneous	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	N-803 IV 0.3/0.5 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Dose Limiting Toxicity

The safety endpoint is the MTD of ALT-803, defined as the dose level below that at which ≥2 of 6 patients experience a DLT.

Posted

Count of Participants

Participants

9 months

ID	Title	Description
OG000	N-803 IV 0.3/0.5 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	N-803 IV 0.3/0.5 ug/kg	ALT-803: N-803 will be administered at the following doses intravenously: 0.3/0.5, 1.0, 3.0, 6.0 ug/kg N-803 will be administered at the following does subcutaneously: 6.0, 10.0, 15.0, 20.0 ug/kg N-803 will be administered intratumorally at a dose of 10.0 ug/kg, followed by N-803 administered subcutaneously at a dose of 15.0 ug/kg. Each treatment cycle consists of 4 weeks on therapy and 2 weeks off. Patients will receive weekly dose of ALT-803 for 4 weeks (Days 1, 8, 15, and 22) used for the identification of the OBD and MTD. After a 2-week rest period (Weeks 5 and 6) and recovery of any dose limiting toxicities to grade 0-1 of Cycle 1, a second 6-week cycle (4 weeks on treatment and 2 weeks off) can begin. After a rest period during Weeks 5 and 6 of Cycle 2, stable or benefitting patients assessed at week 8 +/- 1 may receive up to 2 additional 6-week cycles.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 9, 2016	Jul 1, 2024	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Aug 9, 2016	Jul 15, 2024	SAP_001.pdf

ID	Term
D009369	Neoplasms
D008545	Melanoma
D009362	Neoplasm Metastasis

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type