Hematologic Malignancy, Solid Carcinoma, Solid Tumor, Solid Tumor, Adult
Conditions
Keywords
Benralizumab, hematologic cancer, solid cancer, 20-344, Memorial Sloan Kettering Cancer Center
Brief summary
The purpose of this study is to find out whether the study drug benralizumab is a safe treatment that can reduce the skin side effects caused by cancer treatment by reducing the level of eosinophils in your blood. Reducing the skin side effects of your cancer treatment may improve quality of life and allow participants to continue to receive their usual cancer treatment.
Interventions
DRUGBenralizumab
All eligible patients will receive a benralizumab dose of 30 mg SC administered by a healthcare provider once every 4 weeks for the first 3 doses, followed by once every 8 weeks for 3 additional doses.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have pathologically or cytologically confirmed solid or hematologic cancers. OR * Patient is receiving alpelisib for PIK3CA-Related Overgrowth Spectrum disorder. * Female and male aged 18 to 85 years, inclusively, at the time of Week 0/Day 1 of treatment. * Patients must have a therapy-related CTCAE grade 2/3 (See Appendix A)cutaneous adverse event defined as any cutaneous reaction listed below and blood eosinophil counts of at least .3 K/mcl. * Rash maculo-papular * Bullous dermatitis * Pruritus * Urticaria * Eczema * Patients must plan to continue on culprit drugs (cancer patients). * Patients planning to receive alpelisib indicated for PIK3CA-Related Overgrowth Spectrum disorder OR patients receiving immunotherapy and/or targeted therapy, including but not limited to the following agents, will be eligible for inclusion: * Immunotherapies: ipilimumab, nivolumab, pembrolizumab, avelumab, durvalumab, atezolizumab tremelimumab. * Targeted therapies: trastuzumab, pertuzumab, alpelisib, osimertinib, everolimus, temsirolimus, sorafenib, regorafenib. * Patients using topicals/orals for indication of skin rash/pruritus for at least 7 days should continue using these drugs for the study duration * Adequate bone marrow, liver and renal function: * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer) * Serum creatinine ≤ 1.8 xULN or calculated creatinine clearance \>45 ml/min * Platelet count \> 50 K/mcL , hemoglobin (Hb) \> 8 g/dL, absolute neutrophil count (ANC) \>1.0 K/mcL. Blood transfusion to meet the inclusion criteria will not be allowed. * ECOG performance status 0-1 (see Appendix C). * Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. * Female patients are authorized to participate if they meet the following criteria: * Women of child bearing potential must meet both of the following conditions: * Have a negative serum pregnancy test prior to enrollment and within 14 days prior to administration of the investigational product (IP). * Patient must use an effective form of birth control (confirmed by the Investigator) throughout the study duration and within 16 weeks after last dose of IP. * Female subjects who cannot bear children as evidenced by one or more of the following: * Bilateral Oophorectomy * Bilateral Salpingectomy * Bilateral Salpingectomy-Oophorectomy * Hysterectomy * Menopause (no menses ≥ 1 year prior to treatment) * Surgical Sterilization (i.e., tubal ligation or blockage) Note: If criteria not met, patient should be regarded as having child bearing potential * Subject must be able to receive a subcutaneous injection. * New/worsening ercAE within 90 days prior to study enrollment. Note: This assessment will be performed by the treating investigator.
Exclusion criteria
* Concurrent use of another investigational drug or device for the ercAE (i.e., outside of study treatment) during, or within 4 weeks of treatment. * Patients receiving prednisone ≥ 20mg a day. * Known use of anti-IL-5 agents or biologics for the treatment of asthma which are known to decrease blood eosinophil levels. * Patients cannot use new topicals or medications for indication of pruritus or skin rash * Known history of anaphylaxis to biologic therapy. * A helminthic parasitic infection diagnosed within 24 weeks prior to the first treatment, that had not been treated with, or has failed to respond to, standard of care therapy. * Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy. * Active infection that would impair the ability of the patient to receive study treatment. * Women who are pregnant or breast-feeding. * Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation. * Receipt of live attenuated vaccines 30 days prior to the date of randomization ° Receipt of inactive/killed vaccinations (e.g., inactive influenza) is allowed provided they were not administered within 1 week before/after any investigational product administration. * Known history of allergy or reaction to the investigational product formulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in CTCAE Grade 2/3 Eosinophil-related Cutaneous Adverse Events | 4 weeks | To evaluate the percent reduction in CTCAE grade 2/3 eosinophil-related cutaneous adverse events to grade ≤1 resulting from checkpoint inhibitors (CPIs) or targeted therapies with absolute blood eosinophil counts of at least .3 K/mcl. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAlina Markova, MD
Memorial Sloan Kettering Cancer Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Eosinophil-related Cutaneous Events Study participants will have grade 2/3 eosinophil-related cutaneous adverse events
Benralizumab: All eligible patients will receive a benralizumab dose of 30 mg SC administered by a healthcare provider once every 4 weeks for the first 3 doses, followed by once every 8 weeks for 3 additional doses. | 51 |
| Total | 51 |
Baseline characteristics
| Characteristic | Participants With Eosinophil-related Cutaneous Events |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Region of Enrollment United States | 51 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 29 / 51 |
| other Total, other adverse events | 37 / 51 |
| serious Total, serious adverse events | 4 / 51 |
Outcome results
Primary
Percent Reduction in CTCAE Grade 2/3 Eosinophil-related Cutaneous Adverse Events
To evaluate the percent reduction in CTCAE grade 2/3 eosinophil-related cutaneous adverse events to grade ≤1 resulting from checkpoint inhibitors (CPIs) or targeted therapies with absolute blood eosinophil counts of at least .3 K/mcl.
Time frame: 4 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Eosinophil-related Cutaneous Events | Percent Reduction in CTCAE Grade 2/3 Eosinophil-related Cutaneous Adverse Events | Participants who responded to treatment | 32 Participants |
| Participants With Eosinophil-related Cutaneous Events | Percent Reduction in CTCAE Grade 2/3 Eosinophil-related Cutaneous Adverse Events | Participants who did not respond to treatment | 10 Participants |
| Participants With Eosinophil-related Cutaneous Events | Percent Reduction in CTCAE Grade 2/3 Eosinophil-related Cutaneous Adverse Events | Participants not evaluable | 9 Participants |