A Phase I/II trial of MK-3475 (pembrolizumab) in children’s solid tumors and lymphoma
- Conditions
- Treatment of advanced melanoma or advanced, relapsed or refractory PD-L1 positive malignant solid tumor or lymphoma in children from 6 months to less than 18 years old.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002950-38-SE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 320
1. Be willing and able to provide (and/or their parents or legal
guardians) documented informed consent/assent for the trial.
2. Be between 6 months and less than 18 years of age on the day the screening informed consent is documented.
3. Have histologically or cytologically-documented, locally-advanced, or
metastatic solid malignancy that is incurable and has either (a) failed
prior standard therapy, (b) for which no standard therapy exists, or (c)
standard therapy is not considered appropriate by the patient and
treating physician. There is no limit to the number of prior treatment
regimens.
4. Be able to provide tissue from an archival tissue sample or newly
obtained core or excisional biopsy of a tumor lesion not previously
irradiated (tumors progressing in a prior site of radiation are allowed for characterization, other exceptions may be considered after Sponsor
consultation). Samples that require decalcification are not allowed.
5. Have either advanced melanoma or a PD-L1 positive advanced,
relapsed or refractory solid tumor or lymphoma as determined by IHC in archival formal fixed paraffin embedded tumor (FFPET) or newly
obtained biopsy to qualify for the PD-L1
positive cohorts in Part I and II of this trial.Subjects in the MSI-H solid tumor Cohort must have advanced, relapsed or refractory
solid tumor and local MSI positive test results.
6. Have measurable disease based on RECIST 1.1.
7. Have a performance status as defined below:
• Lansky Play Scale =50 for children up to and including 16 years of age;
• Karnofsky score =50 for children > 16 years of age
•Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
8. Demonstrate adequate organ function
9. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective
• A WOCBP must have a negative highly sensitive pregnancy test (urine) within 72 hours before the first dose of study intervention.
10. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
11. Six of the 12 subjects in a given dose finding /dose confirmation
cohort (ie, Part I) must weigh =16 kg (a minimum of 6 subjects at any
given dose are needed for the IL--2 assay, and subjects must weigh =16
kg in order to provide a specimen for IL-2 analysis).
Subject Inclusion Criteria Relapsed or Refractory Classical Hodgkin
Lymphoma Cohort
12. Be willing and able to provide (and/or their parents or legal
guardians) documented informed consent/assent for the trial.
13. Be between 3 years and less than 18 years of age on the day the screening informed consent is documented.
14. Have relapsed* or refractory† cHL and are either:
- Refractory to front-line therapy;
- High-risk and relapsed from front-line therapy; or
- Relapsed or refractory to second-line therapy
15. Be able to provide lymph node biopsy tissue from an archival sample or newly obtained biopsy of a tumor lesion not previously irradiated
16. Have measurable disease based on IWG
17. Have a performance status as defined below:
- Lansky Play Scale =50 for children up to and including 16 years of age
- Karnofsky score =50 for children >16 years of age
- Patients who are unable to walk becau
1. Is currently participating and receiving study therapy in,or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization.
3. Has recieved prior systemic anti-cancer including investigational agents within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to previously administered agent.
4. Has had prior radiation therapy within 2 weeks of start of trial treatment. Subjects must have recovered from all radiation-related toxicities, not require corticosteriods, and not have had radiation pnemonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotheraphy) to non-CNS disease.
5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (Of note, subjects with tumors involving the brain stem are excluded from the study).
7. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
8. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
10. Has an active infection requiring systemic therapy.
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or known hypersensitivity to any component or analog of the trial treatment, that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 agent or with an agentdirected to another stimulatory or co-inhibitor T-cell receptor (eg, CTLA-4, OX-40, CD137). Subjects with melanoma who previously received treatment with ipilimumab are not excluded.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). No HIV testing is required unless mandated by local health authority.
16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). No testing for Hepatitis B and
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method