Metastatic Renal Cell Carcinoma
Conditions
Brief summary
The main goal of the research study is to determine whether treating renal cell cancer patients with the study drug, hydroxychloroquine, along with IL-2, a standard treatment of kidney cancer that has spread to other parts of the body, can make the cancer easier to kill and eliminate. Another goal is to see how the study drug affects the body's immune cells which fight cancer cells.
Detailed description
The rationale for combining the high dose bolus aldesleukin with hydroxychloroquine includes potential positive interactions on the immune regulatory side, non-overlapping toxicities, and potential for prolongation and increased number of responses based on murine studies conducted at the University of Pittsburgh. This study is a multi-center phase II study designed to estimate the efficacy of combination therapy of standard high dose bolus IL-2 and various doses of hydroxychloroquine therapy in metastatic RCC patients.
Interventions
DRUGHydroxychloroquine
Continuous oral administration (at 600 mg/d) will be initiated prior to the first dose (day -14) given 14 days prior to initiation of the first dose of IL-2 and then daily or twice a day throughout all three treatment courses.
DRUGIL-2
600,000 IU/kg IV bolus q 8 hrs x days 1-5 and 15-19 (maximum 28 doses - 14 per 5 day cycle) of each 84-day course
Sponsors
Prometheus Laboratories
Leonard Appleman
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
* Histologically confirmed metastatic renal cell carcinoma with predominantly clear cell histology. * Have measurable disease by RECIST 1.1 criteria. For example, this would include tumor in the lung, liver, and retroperitoneum. Bone disease is difficult to follow and quantify and as a sole site would not be acceptable. * Patients must be at least 4 weeks from radiation or surgery and recovered from all ill effects. * Age ≥18 years. * Karnofsky Performance Status ≥80%. * Adequate end organ function: 1. Hematologic: ANC ≥ 1000cells/uL, platelets ≥ 100,000/uL, hemoglobin ≥ 9g/dl (pre transfusion values used for prognostic factor, can be transfused or use recombinant erythropoietin growth factors but must not have active bleeding). 2. Liver: AST ≤ 2 x ULN (upper limit of normal), serum total bilirubin ≤ 2 x ULN (except for patients with Gilbert's Syndrome). 3. Renal: serum creatinine ≤ 1.5 mg/dL or estimated creatinine clearance ≥ 60ml/min using Cockcroft-Gault estimation using the formula per protocol. 4. Pulmonary: FEV1 ≥ 2.0 liters or ≥ 75% of predicted for height and age. (PFTs are required for patients over 50 or with significant pulmonary or smoking history defined as \>20 pack years or history of COPD/emphysema). 5. Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than one year prior to entry, serious cardiac arrhythmias, or unstable angina. Patients who are over 40 or have had previous cardiac disease will be required to have a negative or low probability cardiac stress test for cardiac ischemia. * Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study. * Appropriate contraception in both genders. * The patient must be competent and have signed informed consent. * CNS: No history of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases.
Exclusion criteria
* Patients who have previously received IL-2 are NOT eligible. Patients on HCQ in neoadjuvant protocols or in the past for clinical indications ARE eligible, as are patients who have previously received CTLA-4 and/or PD-1/PD-L1 antibodies. * Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence or breast CIS. * In patients with a prior history of invasive malignancy, less than five years in complete remission. * Positive serology for HIV, hepatitis B or hepatitis C. * Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen. * Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 2 weeks must have passed since the last dose). * History of inflammatory bowel disease or other serious autoimmune disease. (Not including thyroiditis and rheumatoid arthritis). Patients already on hydroxychloroquine for such disorders are not eligible. * Patients with organ allografts. * Uncontrolled hypertension (BP \>150/100 mmHg). * Proteinuria dipstick \> 3+ or ≥ 2gm/24 hours. * Urine protein:creatinine ratio ≥ 1.0 at screening. * Major surgery, open biopsy, significant traumatic injury within 28 days of starting treatment or anticipation of need for major surgical procedure during the course of the study. * Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to starting treatment. Central venous catheter placements are permitted. * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to starting treatment. * Serious, non-healing wound, ulcer, or bone fracture. * History of tumor-related or other serious hemorrhage, bleeding diathesis, or underlying coagulopathy. * History of deep venous thrombosis, clinically significant peripheral vascular disease, or other thrombotic event. * Inability to comply with study and/or follow-up procedures. * Individuals with known history of glucose 6 phosphate deficiency are excluded from the trial (possible issue with HCQ tolerance). * Patients with previously documented macular degeneration or diabetic retinopathy are excluded from the trial. * Baseline EKG with QTc \> 470 msec (including subjects on medication). Subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at Either 1,200 mg/d or 600 mg/d) (All Patients) | Up to 3 years | Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression. |
| Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 1,200 mg/d | Up to 3 years | Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression. |
| Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 600 mg/d | Up to 3 years | Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Doses of IL-2 + HCQ | Up to 3 years | Number of doses of IL-2 administered during the first course of therapy. |
| Frequency of Grade III and Grade IV Toxicities | Up to 3 years | Number of specified categories of grade III and IV or unexpected or rare toxicities occurring during the first course (up until the end of cycle 1) of IL-2 treatment. |
| Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced | Up to 3 years | Number of participants who experienced Grade 2-5 adverse events that were at least possibly related to study treatment. |
| Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced | Up to 3 years | Number of participants who experienced Grade 2-5 adverse events that were at least probably related to study treatment. |
| Serum Lactate Dehydrogenase | Up to 2 years | Number of participants with either high serum lactate dehydrogenase (\> 1.5 times upper limit of normal) or normal lactate dehydrogenase. |
| Hemoglobin Levels | Up to 3 years | Low hemoglobin levels (less than the lower limit of normal (13.2 g/dL)) are considered to be unfavorable. |
| Serum Calcium Levels (Corrected) | Up to 3 years | Number of patients with either normal or high serum calcium levels. High serum calcium levels are considered to be clinically unfavorable. |
| Worst Grade of Adverse Event Experienced | Up to 3 years | Number of participants who experienced Grade 2-5 adverse events. |
| Number of Participants With Low Karnofsky Performance Status | Up to 3 years | Karnofsky performance status is a standard way of measuring the ability of cancer patients to perform ordinary tasks. The Karnofsky Performance Status scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities. Karnofsky Performance Status may be used to determine a patient's prognosis, to measure changes in a patient's ability to function, or to decide if a patient should be included in the trial. A low Karnofsky performance status (\<80%) is considered to be unfavorable. |
| Natural Killer (NK) Cells | Up to 3 years | Percentage of Natural Killer (NK) cells per ml of blood. NK cells are lymphocytes with the ability to kill tumor cells without deliberate immunization or activation. |
| Myeloid Derived Suppressor Cell (MDSC) | Up to 3 years | Percentage of Myeloid Derived Suppressor Cell per ml of blood. MDSC immune cells originate from bone marrow stem cells and strongly expand in cancer. |
| Regulatory T Cells (Treg) | Up to 3 years | Percentage of Regulatory T cells per ml of blood. High levels of Tregs in the tumor microenvironment are associated with poor prognosis in many cancers by suppressing the body's anti-tumor immune response. |
| Plasmacytoid Dendritic Cells (pDC) | Up to 3 years | Percentage of Plasmacytoid dendritic cells per ml of blood. In cancer, pDC are malignant immune cells that demonstrate an impaired response that can contribute to the establishment of an immunosuppressive tumor microenvironment. |
| T-cell Lymphocytes | Up to 3 years | Percentage of T-cell lymphocytes in blood as cells per ml. T-cells are a subtype of white blood cells which play a key role in the immune system and fighting cancer. |
| Conventional Dendritic Cells (cDC) | Up to 3 years | Percentage of Conventional Dendritic Cells (cDC) per ml of blood. cDC reside in tissues and once activated, migrate to draining lymph nodes to promote adaptive immune responses. |
| Prior Nephrectomy | Up to 3 years | Number of patients with history of a prior nephrectomy (surgical removal of a kidney) or no history of a prior nephrectomy. |
| Overall Survival (OS) | Up to 3 years | Time from date of first protocol treatment until the date of death, or censored at date of last contact. |
| Progression-free Survival (PFS) | Up to 3 years | Time from the date of first protocol treatment until the date disease progression criteria are met (in responding patients progression criteria uses the reference of the smallest measurements recorded since the treatment started) or is censored at date of last disease assessment for those who have not progressed. Per RECIST 1.1, Progressive Disease (PD) is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine (HCQ) (1,200 mg/d or 600 mg/d) + IL-2 One course of treatment (84 days) will consist of high dose (600,000 IU/kg) bolus IL-2 administered intravenously every 8 hours on days 1-5 and 15-19 (maximum 14 doses/5 days of administration) and hydroxychloroquine (HCQ) orally started two weeks prior to IL-2 infusions and continued while able to take oral medication for up to 3 courses.
Hydroxychloroquine: Continuous oral administration (at 1,200 mg/d for initial (13) patients, then 600 mg/d for next (17) patients) was initiated prior to the first dose (day -14) given 14 days prior to initiation of the first dose of IL-2 and then daily or twice a day throughout all three treatment courses.
IL-2: 600,000 IU/kg IV bolus q 8 hrs x days 1-5 and 15-19 (maximum 28 doses - 14 per 5 day cycle) of each 84-day course
Note: Patients were initially treated at 1200 mg/d HCQ, but after several unexpected adverse events, the dose of HCQ was reduced to 600 mg/d. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Hydroxychloroquine (HCQ) (1,200 mg/d or 600 mg/d) + IL-2 |
|---|---|
| Age, Continuous 1200 mg/d HCQ | 58.2 years |
| Age, Continuous 600 mg/d HCQ | 56.5 years |
| Karnofsky Performance Status (KPS) KPS Score - 1200 mg/d HCQ KPS Score of 100 | 1 Participants |
| Karnofsky Performance Status (KPS) KPS Score - 1200 mg/d HCQ KPS Score of 80 | 11 Participants |
| Karnofsky Performance Status (KPS) KPS Score - 1200 mg/d HCQ KPS Score of 90 | 1 Participants |
| Karnofsky Performance Status (KPS) KPS Score - 600 mg/d HCQ KPS Score of 100 | 4 Participants |
| Karnofsky Performance Status (KPS) KPS Score - 600 mg/d HCQ KPS Score of 80 | 13 Participants |
| Karnofsky Performance Status (KPS) KPS Score - 600 mg/d HCQ KPS Score of 90 | 0 Participants |
| Race (NIH/OMB) All Patients American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) All Patients Asian | 0 Participants |
| Race (NIH/OMB) All Patients Black or African American | 0 Participants |
| Race (NIH/OMB) All Patients More than one race | 0 Participants |
| Race (NIH/OMB) All Patients Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) All Patients Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) All Patients White | 30 Participants |
| Sex: Female, Male 1200 mg/d HCQ Female | 4 Participants |
| Sex: Female, Male 1200 mg/d HCQ Male | 9 Participants |
| Sex: Female, Male 600 mg/d HCQ Female | 4 Participants |
| Sex: Female, Male 600 mg/d HCQ Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 13 | 2 / 17 |
| other Total, other adverse events | 13 / 13 | 17 / 17 |
| serious Total, serious adverse events | 12 / 13 | 17 / 17 |
Outcome results
Primary
Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 1,200 mg/d
Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Time frame: Up to 3 years
Population: Patients with metastatic RCC treated with IL-2 combined with hydroxychloroquine (HCQ) 1,200 mg/d who were evaluable for clinical response.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 1,200 mg/d | Progressed Disease | 5 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 1,200 mg/d | Stable Disease | 6 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 1,200 mg/d | Partial Response | 1 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 1,200 mg/d | Complete Response | 0 Participants |
Primary
Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 600 mg/d
Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Time frame: Up to 3 years
Population: Patients with metastatic RCC treated with IL-2 combined with hydroxychloroquine (HCQ) 600 mg/d who were evaluable for clinical response.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 600 mg/d | Progressed Disease | 4 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 600 mg/d | Stable Disease | 8 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 600 mg/d | Partial Response | 2 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at 600 mg/d | Complete Response | 3 Participants |
Primary
Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at Either 1,200 mg/d or 600 mg/d) (All Patients)
Clinical Response: per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Time frame: Up to 3 years
Population: Patients with metastatic RCC treated with IL-2 combined with hydroxychloroquine (HCQ at either 1,200 mg/d or 600 mg/d) who were evaluable for clinical response. Note: Patients were initially treated at 1200 mg/d HCQ, but after several unexpected adverse events, dosing was reduced to 600 mg/d.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at Either 1,200 mg/d or 600 mg/d) (All Patients) | Progressed Disease - All Patients | 9 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at Either 1,200 mg/d or 600 mg/d) (All Patients) | Stable Disease - All Patients | 14 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at Either 1,200 mg/d or 600 mg/d) (All Patients) | Partial Response - All Patients | 3 Participants |
| Hydroxychloroquine + IL-2 | Clinical Response - IL-2 Combined With Hydroxychloroquine (HCQ) at Either 1,200 mg/d or 600 mg/d) (All Patients) | Complete Response - All Patients | 3 Participants |
Secondary
Conventional Dendritic Cells (cDC)
Percentage of Conventional Dendritic Cells (cDC) per ml of blood. cDC reside in tissues and once activated, migrate to draining lymph nodes to promote adaptive immune responses.
Time frame: Up to 3 years
Population: Patients that received study treatment for whom Conventional Dendritic Cells (cDC) were able to be measured.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | Conventional Dendritic Cells (cDC) | 0.6 percentage of cells/mL |
Secondary
Frequency of Grade III and Grade IV Toxicities
Number of specified categories of grade III and IV or unexpected or rare toxicities occurring during the first course (up until the end of cycle 1) of IL-2 treatment.
Time frame: Up to 3 years
Population: Patients that received at least one dose (cycle) of study treatment (IL-2 + either 1,200 HCQ or 600 mg/d HCQ) and experienced specified categories of toxicities.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hydroxychloroquine + IL-2 | Frequency of Grade III and Grade IV Toxicities | Hypotension | 5 events |
| Hydroxychloroquine + IL-2 | Frequency of Grade III and Grade IV Toxicities | Gastrointestinal | 1 events |
| Hydroxychloroquine + IL-2 | Frequency of Grade III and Grade IV Toxicities | Hematologic | 1 events |
| Hydroxychloroquine + IL-2 | Frequency of Grade III and Grade IV Toxicities | Pulmonary | 1 events |
| Hydroxychloroquine + IL-2 | Frequency of Grade III and Grade IV Toxicities | Renal/electrolytes | 4 events |
| Hydroxychloroquine + IL-2 | Frequency of Grade III and Grade IV Toxicities | Psychiatric | 3 events |
Secondary
Hemoglobin Levels
Low hemoglobin levels (less than the lower limit of normal (13.2 g/dL)) are considered to be unfavorable.
Time frame: Up to 3 years
Population: Patient that received study treatment for whom hemoglobin levels were able to be measured from clinical samples and determined to be either normal or low.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydroxychloroquine + IL-2 | Hemoglobin Levels | Low hemoglobin level | 1200 mg/d HCQ | 6 Participants |
| Hydroxychloroquine + IL-2 | Hemoglobin Levels | Low hemoglobin level | 600 mg/d HCQ | 3 Participants |
| Hydroxychloroquine + IL-2 | Hemoglobin Levels | Normal hemoglobin level | 1200 mg/d HCQ | 7 Participants |
| Hydroxychloroquine + IL-2 | Hemoglobin Levels | Normal hemoglobin level | 600 mg/d HCQ | 14 Participants |
Secondary
Myeloid Derived Suppressor Cell (MDSC)
Percentage of Myeloid Derived Suppressor Cell per ml of blood. MDSC immune cells originate from bone marrow stem cells and strongly expand in cancer.
Time frame: Up to 3 years
Population: Patients that received study treatment for whom MDSC were able to be measured.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | Myeloid Derived Suppressor Cell (MDSC) | 11.3 percentage of cells/mL |
Secondary
Natural Killer (NK) Cells
Percentage of Natural Killer (NK) cells per ml of blood. NK cells are lymphocytes with the ability to kill tumor cells without deliberate immunization or activation.
Time frame: Up to 3 years
Population: Patients that received study treatment for whom Natural Killer (NK) cells were able to be measured.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | Natural Killer (NK) Cells | 38.4 percentage of cells |
Secondary
Number of Doses of IL-2 + HCQ
Number of doses of IL-2 administered during the first course of therapy.
Time frame: Up to 3 years
Population: Patients that received at least one dose of study treatment (IL-2 + either 1,200 HCQ or 600 mg/d HCQ).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Hydroxychloroquine + IL-2 | Number of Doses of IL-2 + HCQ | 1200 mg/d HCQ | 12.8 doses |
| Hydroxychloroquine + IL-2 | Number of Doses of IL-2 + HCQ | 600 mg/d HCQ | 13.2 doses |
Secondary
Number of Participants With Low Karnofsky Performance Status
Karnofsky performance status is a standard way of measuring the ability of cancer patients to perform ordinary tasks. The Karnofsky Performance Status scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities. Karnofsky Performance Status may be used to determine a patient's prognosis, to measure changes in a patient's ability to function, or to decide if a patient should be included in the trial. A low Karnofsky performance status (\<80%) is considered to be unfavorable.
Time frame: Up to 3 years
Population: Patient that received study treatment for whom Karnofsky performance status was able to be assessed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydroxychloroquine + IL-2 | Number of Participants With Low Karnofsky Performance Status | 1200 mg/d HCQ | 0 Participants |
| Hydroxychloroquine + IL-2 | Number of Participants With Low Karnofsky Performance Status | 600 mg/d HCQ | 0 Participants |
Secondary
Overall Survival (OS)
Time from date of first protocol treatment until the date of death, or censored at date of last contact.
Time frame: Up to 3 years
Population: Patients with metastatic RCC treated with IL-2 combined with hydroxychloroquine (HCQ).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | Overall Survival (OS) | NA months |
Secondary
Plasmacytoid Dendritic Cells (pDC)
Percentage of Plasmacytoid dendritic cells per ml of blood. In cancer, pDC are malignant immune cells that demonstrate an impaired response that can contribute to the establishment of an immunosuppressive tumor microenvironment.
Time frame: Up to 3 years
Population: Patients that received study treatment for whom Plasmacytoid dendritic Cells (pDC) were able to be measured.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | Plasmacytoid Dendritic Cells (pDC) | 0.3 percentage of cells/mL |
Secondary
Prior Nephrectomy
Number of patients with history of a prior nephrectomy (surgical removal of a kidney) or no history of a prior nephrectomy.
Time frame: Up to 3 years
Population: Patients that received study treatment, with or without a history of nephrectomy (surgical removal of a kidney).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydroxychloroquine + IL-2 | Prior Nephrectomy | No Prior Nephrectomy | 600 mg/d HCQ | 3 Participants |
| Hydroxychloroquine + IL-2 | Prior Nephrectomy | No Prior Nephrectomy | 1200 mg/d HCQ | 0 Participants |
| Hydroxychloroquine + IL-2 | Prior Nephrectomy | Prior Nephrectomy | 600 mg/d HCQ | 14 Participants |
| Hydroxychloroquine + IL-2 | Prior Nephrectomy | Prior Nephrectomy | 1200 mg/d HCQ | 13 Participants |
Secondary
Progression-free Survival (PFS)
Time from the date of first protocol treatment until the date disease progression criteria are met (in responding patients progression criteria uses the reference of the smallest measurements recorded since the treatment started) or is censored at date of last disease assessment for those who have not progressed. Per RECIST 1.1, Progressive Disease (PD) is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
Time frame: Up to 3 years
Population: Patients with metastatic RCC treated with IL-2 combined with hydroxychloroquine (HCQ) at either 600 mg/d or 1,200 mg/d.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | Progression-free Survival (PFS) | 5.5 months |
Secondary
Regulatory T Cells (Treg)
Percentage of Regulatory T cells per ml of blood. High levels of Tregs in the tumor microenvironment are associated with poor prognosis in many cancers by suppressing the body's anti-tumor immune response.
Time frame: Up to 3 years
Population: Patients that received study treatment for whom Regulatory T cells (Treg) were able to be measured.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | Regulatory T Cells (Treg) | 10.5 percentage of cells/mL |
Secondary
Serum Calcium Levels (Corrected)
Number of patients with either normal or high serum calcium levels. High serum calcium levels are considered to be clinically unfavorable.
Time frame: Up to 3 years
Population: Patients that received study treatment for whom serum calcium levels were able to be measured from clinical samples and determined to be either normal or high.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydroxychloroquine + IL-2 | Serum Calcium Levels (Corrected) | Normal Calcium | 1200 mg/d HCQ | 13 Participants |
| Hydroxychloroquine + IL-2 | Serum Calcium Levels (Corrected) | Normal Calcium | 600 mg/d HCQ | 14 Participants |
| Hydroxychloroquine + IL-2 | Serum Calcium Levels (Corrected) | High Calcium | 1200 mg/d HCQ | 0 Participants |
| Hydroxychloroquine + IL-2 | Serum Calcium Levels (Corrected) | High Calcium | 600 mg/d HCQ | 3 Participants |
Secondary
Serum Lactate Dehydrogenase
Number of participants with either high serum lactate dehydrogenase (\> 1.5 times upper limit of normal) or normal lactate dehydrogenase.
Time frame: Up to 2 years
Population: Patients that received study treatment for whom LDH was able to be measured from clinical samples and determined to be either normal or high.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydroxychloroquine + IL-2 | Serum Lactate Dehydrogenase | Normal LDH | 1200 mg/d HCQ | 11 Participants |
| Hydroxychloroquine + IL-2 | Serum Lactate Dehydrogenase | Normal LDH | 600 mg/d HCQ | 17 Participants |
| Hydroxychloroquine + IL-2 | Serum Lactate Dehydrogenase | High LDH | 1200 mg/d HCQ | 2 Participants |
| Hydroxychloroquine + IL-2 | Serum Lactate Dehydrogenase | High LDH | 600 mg/d HCQ | 0 Participants |
Secondary
T-cell Lymphocytes
Percentage of T-cell lymphocytes in blood as cells per ml. T-cells are a subtype of white blood cells which play a key role in the immune system and fighting cancer.
Time frame: Up to 3 years
Population: Patients that received study treatment for whom T-Cells were able to be measured.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxychloroquine + IL-2 | T-cell Lymphocytes | 63.9 percentage of cells/mL |
Secondary
Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced
Number of participants who experienced Grade 2-5 adverse events that were at least possibly related to study treatment.
Time frame: Up to 3 years
Population: Patients that received at least one dose of study treatment (IL-2 + either 1,200 HCQ or 600 mg/d HCQ).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced | 1200 mg/d HCQ | Grade 2 adverse event | 1 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced | 1200 mg/d HCQ | Grade 3 adverse event | 5 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced | 1200 mg/d HCQ | Grade 4 adverse event | 7 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced | 600 mg/d HCQ | Grade 2 adverse event | 0 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced | 600 mg/d HCQ | Grade 3 adverse event | 4 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Possibly Related to Treatment Experienced | 600 mg/d HCQ | Grade 4 adverse event | 13 Participants |
Secondary
Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced
Number of participants who experienced Grade 2-5 adverse events that were at least probably related to study treatment.
Time frame: Up to 3 years
Population: Patients that received at least one dose of study treatment (IL-2 + either 1,200 HCQ or 600 mg/d HCQ).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced | 1200 mg/d HCQ | Grade 2 adverse event | 1 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced | 1200 mg/d HCQ | Grade 3 adverse event | 5 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced | 1200 mg/d HCQ | Grade 4 adverse event | 7 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced | 600 mg/d HCQ | Grade 2 adverse event | 2 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced | 600 mg/d HCQ | Grade 3 adverse event | 4 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event At Least Probably Related to Treatment Experienced | 600 mg/d HCQ | Grade 4 adverse event | 11 Participants |
Secondary
Worst Grade of Adverse Event Experienced
Number of participants who experienced Grade 2-5 adverse events.
Time frame: Up to 3 years
Population: Patients that received at least one dose of study treatment (IL-2 + either 1,200 HCQ or 600 mg/d HCQ).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 1200 mg/d HCQ | Grade 2 adverse event | 1 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 1200 mg/d HCQ | Grade 3 adverse event | 4 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 1200 mg/d HCQ | Grade 4 adverse event | 7 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 1200 mg/d HCQ | Grade 5 adverse event | 1 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 600 mg/d HCQ | Grade 2 adverse event | 0 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 600 mg/d HCQ | Grade 3 adverse event | 4 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 600 mg/d HCQ | Grade 4 adverse event | 13 Participants |
| Hydroxychloroquine + IL-2 | Worst Grade of Adverse Event Experienced | 600 mg/d HCQ | Grade 5 adverse event | 0 Participants |