AIDS-Related Kaposi Sarcoma, HIV Infection, Kaposi Sarcoma
Conditions
Brief summary
This phase I trial studies the best dose and effects of NT-I7 in treating Kaposi sarcoma in patients with or without HIV. NT-I7 works by using a patient's immune system to fight cancer. It is made in a laboratory and is used to boost, direct, or restore the body's natural defenses against cancer. NT-I7 may work better in treating Kaposi sarcoma.
Detailed description
OUTLINE: This is a dose-escalation study. Patients receive efineptakin alfa intramuscularly (IM) on day 1. Cycles repeat every 9 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up on day 30 (+/- 7 days) and then every 12 weeks for 12 months.
Interventions
BIOLOGICALEfineptakin alfa
Given IM
Sponsors
Cancer Immunotherapy Trials Network (CITN)
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed Kaposi sarcoma * Patients must have evaluable disease. Note: Kaposi sarcoma will be evaluated using a modified version (consistent with National Cancer Institute \[NCI\] studies) of the Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group (ACTG) Oncology Committee staging and response definitions for KS * No upper or lower limit on the number of prior therapies or stage of disease * HIV-positive patients must have been on effective anti-retroviral (ART) therapy for at least 3 months prior to enrollment, with persistent KS affecting quality of life due to either T1 disease or T0 disease with inadequate disease regression on ART alone * HIV-positive patients must have undetectable HIV viral loads =\< 40 copies/mL measured using a Food and Drug Administration (FDA)-approved commercial assay with lower limit of detection between =\< 20 copies/mL and =\< 40 copies/mL * Patients with visceral involvement must: * Meet other eligibility criteria * Have any/all associated tumor associated symptoms =\< grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) criteria; and/or * Require no immediate intervention (e.g. mild oozing of oral KS not an
Exclusion criteria
) * Patients must provide newly obtained core, punch, or excisional biopsy of a tumor lesion obtained up to 28 days prior to treatment initiation. An archival tumor sample obtained within 1 year of screening is allowed if pre treatment biopsy is deemed unsafe or technically not feasible * Patients must be \>= 18 years of age on day of signing informed consent document. Because no dosing or adverse event data are currently available on the use of NT-I7 in patients \< 18 years of age, children are excluded from this study but will be eligible for future pediatric trials * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Leukocytes \>= 2,500/mcL * Absolute neutrophil count \>= 1,000/mcL * Platelets \>= 100,000/mcL * Hemoglobin \>= 9/dL * Total bilirubin =\< 1.5 institutional upper limit of normal (ULN) OR \< 3 x institutional ULN for Gilbert's syndrome or HIV protease inhibitors * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional ULN * Creatinine =\< 2 x institutional ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 by Cockcroft-Gault. At the discretion of the treating physician, a 24-hour urine creatinine clearance could be obtained and utilized as the gold standard if creatinine clearance by Cockcroft-Gault is \< 30 and prevents patient enrollment on the trial * Patients with chronic hepatitis B virus (HBV) infection must be on suppressive antiviral therapy * Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load due to prior treatment or natural resolution * Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of the study agent. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * The effects of NT-I7 on the developing human fetus are unknown. For this reason and because NT-I7 may have an adverse effect on pregnancy and poses risk to the human fetus, 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 for 90 days after the last dose of study treatment. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 90 days after completion of NT-I7 administration * Ability to understand and the willingness to sign a written informed consent document
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events | Up to 30 days after last dose of NT-I7, approximately 31 weeks total | Measured by Common Terminology Criteria for Adverse Events version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR). | 12 months | Defined as the proportion of participants who achieved Complete Response (CR) or Partial Response (PR) according to modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group Criteria (ACTG) criteria. |
| Duration of Response (DOR) | Up to 1 year | Measured in participants who obtain a partial response or better and defined as time from the best response within the first 36 weeks of therapy until disease progression or censoring. Kaplan Meier survival estimates constructed for each of these survival endpoints with 95% confidence intervals (CIs), for up to 1 year following initiation of treatment in all participants. |
| Progression-free Survival (PFS) | Assessed up to 1 year | Defined as the time from administration of the first dose of NT-I7 until disease progression or death or censoring. Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% CIs, for up to 1 year following initiation of treatment in all participants. |
| Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood | From pre-administration to each time point following first administration (1, 4, and 9 weeks) | For analysis of circulating lymphocytes, we will describe fold-change (median and range) in blood ALC. Fold change from baseline is defined as the ratio of the value at the visit to that at baseline. |
| Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood. | From pre-administration to each time point following first administration (1, 4, and 9 weeks) | Described by fold-change (median and range) in blood CD4+ T cells. Fold change from baseline is defined as the ratio of the value at the visit to that at baseline. |
| Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood. | From pre-administration to each time point following first administration (1, 4, and 9 weeks) | Described by fold-change (median and range) in blood CD8+ T cells. Fold change from baseline is defined as the ratio of the value at the visit to that at baseline. |
| Overall Survival (OS) | Assessed up to 1 year following initiation of treatment | From administration of the first dose of NT-I7 until death or censoring. Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% CIs. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of NT-I7 | Up to 12 months after last dose of NT-I7 | The proportion of participants developing neutralizing antibodies will be summarized. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 Participants receive 480 µg/kg NT-I7 (Efineptakin alfa) IM on day 1. Cycles repeat every 9 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
NT-I7 (Efineptakin alfa): Given IM | 6 |
| NT-I7 (Efineptakin Alfa) Dose Level 2 Participants receive 960 µg/kg NT-I7 (Efineptakin alfa) IM on day 1. Cycles repeat every 9 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
NT-I7 (Efineptakin alfa): Given IM | 2 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Study Terminated | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | NT-I7 (Efineptakin Alfa) Dose Level 1 | NT-I7 (Efineptakin Alfa) Dose Level 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 2 Participants | 7 Participants |
| Age, Continuous | 57.2 years STANDARD_DEVIATION 7.2 | 37.0 years STANDARD_DEVIATION 5.7 | 52.1 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 1 Participants | 6 Participants |
| Region of Enrollment United States | 6 participants | 2 participants | 8 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 2 |
| other Total, other adverse events | 6 / 6 | 2 / 2 |
| serious Total, serious adverse events | 1 / 6 | 1 / 2 |
Outcome results
Primary
Percentage of Participants With Adverse Events
Measured by Common Terminology Criteria for Adverse Events version 5.0.
Time frame: Up to 30 days after last dose of NT-I7, approximately 31 weeks total
Population: Analysis is conducted on all enrolled participants who received at least one dose of NT-I7.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Percentage of Participants With Adverse Events | 100 percentage of participants |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Percentage of Participants With Adverse Events | 100 percentage of participants |
Secondary
Duration of Response (DOR)
Measured in participants who obtain a partial response or better and defined as time from the best response within the first 36 weeks of therapy until disease progression or censoring. Kaplan Meier survival estimates constructed for each of these survival endpoints with 95% confidence intervals (CIs), for up to 1 year following initiation of treatment in all participants.
Time frame: Up to 1 year
Population: Analysis is conducted on all enrolled participants who received at least one dose of NT-I7 and provided at least one post-baseline response assessment, and did not discontinue study treatment prior to the first protocol-specified timepoint for evaluation of response to therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Duration of Response (DOR) | NA months |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Duration of Response (DOR) | NA months |
Secondary
Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood
For analysis of circulating lymphocytes, we will describe fold-change (median and range) in blood ALC. Fold change from baseline is defined as the ratio of the value at the visit to that at baseline.
Time frame: From pre-administration to each time point following first administration (1, 4, and 9 weeks)
Population: Analysis is conducted on all enrolled participants who received at least one dose of NT-I7 and provided at least one post-baseline response assessment, and did not discontinue study treatment prior to the first protocol-specified timepoint for evaluation of response to therapy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood | Week 1 | 1.06 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood | Week 4 | 3.20 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood | Week 9 | 3.01 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood | Week 1 | 1.15 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood | Week 4 | 3.93 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of Absolute Lymphocyte Counts (ALC) in Blood | Week 9 | 3.24 No units, median and IQR of ratios |
Secondary
Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood.
Described by fold-change (median and range) in blood CD4+ T cells. Fold change from baseline is defined as the ratio of the value at the visit to that at baseline.
Time frame: From pre-administration to each time point following first administration (1, 4, and 9 weeks)
Population: Analysis is conducted on all enrolled participants who received at least one dose of NT-I7 and provided at least one post-baseline response assessment, and did not discontinue study treatment prior to the first protocol-specified timepoint for evaluation of response to therapy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood. | Week 1 | 1.26 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood. | Week 4 | 4.46 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood. | Week 9 | 3.26 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood. | Week 9 | 4.45 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood. | Week 1 | 1.19 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of CD4+ T Cells in Blood. | Week 4 | 6.30 No units, median and IQR of ratios |
Secondary
Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood.
Described by fold-change (median and range) in blood CD8+ T cells. Fold change from baseline is defined as the ratio of the value at the visit to that at baseline.
Time frame: From pre-administration to each time point following first administration (1, 4, and 9 weeks)
Population: Analysis is conducted on all enrolled participants who received at least one dose of NT-I7 and provided at least one post-baseline response assessment, and did not discontinue study treatment prior to the first protocol-specified timepoint for evaluation of response to therapy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood. | Week 4 | 3.25 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood. | Week 9 | 2.53 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood. | Week 1 | 0.89 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood. | Week 4 | 4.12 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood. | Week 1 | 1.29 No units, median and IQR of ratios |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Effect of NT-I7 on Kinetics of CD8+ T Cells in Blood. | Week 9 | 3.28 No units, median and IQR of ratios |
Secondary
Objective Response Rate (ORR).
Defined as the proportion of participants who achieved Complete Response (CR) or Partial Response (PR) according to modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group Criteria (ACTG) criteria.
Time frame: 12 months
Population: Analysis is conducted on all enrolled participants who received at least one dose of NT-I7 and provided at least one post-baseline response assessment, and did not discontinue study treatment prior to the first protocol-specified timepoint for evaluation of response to therapy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Objective Response Rate (ORR). | Objective Response Rate (CR+PR) | 1 Participants |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Objective Response Rate (ORR). | Complete Response (CR) | 0 Participants |
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Objective Response Rate (ORR). | Partial Response (PR) | 1 Participants |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Objective Response Rate (ORR). | Partial Response (PR) | 2 Participants |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Objective Response Rate (ORR). | Objective Response Rate (CR+PR) | 2 Participants |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Objective Response Rate (ORR). | Complete Response (CR) | 0 Participants |
Secondary
Overall Survival (OS)
From administration of the first dose of NT-I7 until death or censoring. Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% CIs.
Time frame: Assessed up to 1 year following initiation of treatment
Population: Analysis is conducted on all enrolled and treated participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Overall Survival (OS) | NA months |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Overall Survival (OS) | NA months |
Secondary
Progression-free Survival (PFS)
Defined as the time from administration of the first dose of NT-I7 until disease progression or death or censoring. Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% CIs, for up to 1 year following initiation of treatment in all participants.
Time frame: Assessed up to 1 year
Population: Analysis is conducted on all enrolled participants who received at least one dose of NT-I7 and provided at least one post-baseline response assessment, and did not discontinue study treatment prior to the first protocol-specified timepoint for evaluation of response to therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NT-I7 (Efineptakin Alfa) Dose Level 1 | Progression-free Survival (PFS) | NA months |
| NT-I7 (Efineptakin Alfa) Dose Level 2 | Progression-free Survival (PFS) | NA months |
Other Pre-specified
Immunogenicity of NT-I7
The proportion of participants developing neutralizing antibodies will be summarized.
Time frame: Up to 12 months after last dose of NT-I7