A phase II trial of MK-3475 (pembrolizumab) in children and young adults with classical Hodgkin lymphoma
- Conditions
- cHL in children and young adultsMedDRA version: 20.1Level: LLTClassification code 10080208Term: Classical Hodgkin lymphomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001123-53-CZ
- Lead Sponsor
- Merck Sharp & Dohme Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 440
1. Must be between the ages of 3 and 25 on the day of signing informed consent/assent
2. Group 1: Must have newly diagnosed, pathologically confirmed cHL at Stages IA, IB and IIA without bulky disease
Bulky disease is defined as the presence of any of the following:
- Nodal area >6cm OR
- Mass/thoracic diameter >one-third
Group 2: Must have newly diagnosed, pathologically confirmed cHL at Stages IIEB, IIIEA, IIIEB, IIIB, IVA and IVB
3. Must have measurable disease per investigator assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Measurable disease is defined as the existence of at least one measurable nodal lesion present, defined as a lymph node or nodal mass that is either >15 mm in longest diameter or >10 mm in short axis on a diagnostic CT, and appropriate for reproducible measurements. A lesion that appears measurable, but is located in an area that was previously irradiated, can be considered measurable if it has shown growth since the completion of radiation
4.Male participants are eligible to participate if they agree to the following during the intervention period:
- Refrain from donating sperm
PLUS either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent
OR
- Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
o Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not
currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom
during each episode of penile-vaginal penetration.
o Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the
contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
5. female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 7 during the intervention period and for at least 120 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
o A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study
intervention.
o If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the se
1. Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. Participants who have had allogeneic hematopoietic stem cell transplant greater than 5 years ago are eligible as long as there are no symptoms of graft-versus-host disease (GVHD)
2. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
3. Baseline left ventricular ejection fraction value <50% or shortening fraction of <27%
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (ie, CTLA-4, OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK-3475) clinical study
5. Has received any prior anti-cancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device before the first dose of study treatment, or has not recovered (=Grade 1 or at baseline) from AEs due to previously administered agents
6.Is expected to receive a live vaccine within 30 days prior to the first dose of pembrolizumab Administration of killed vaccines is allowed
7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
8. Has a diagnosis of lymphocyte-predominant HL
9. Has a diagnosis of immunodeficiency or is expected to be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab. The use of physiologic doses of corticosteroids (up to 5 mg/m2/day prednisone equivalent) may be approved after consultation with the Sponsor
10. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy
11. Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator at the time of diagnosis
12. Has severe hypersensitivity (=Grade 3) to any study therapies including any excipients
13. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
15. Has an active infection requiring systemic therapy
16. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen re
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