A phase II trial of MK-3475 (pembrolizumab) in children and young adults with classical Hodgkin lymphoma

Phase 1

Conditions: cHL in children and young adults
MedDRA version: 20.1Level: LLTClassification code 10080208Term: Classical Hodgkin lymphomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-001123-53-DE

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 340

Inclusion Criteria

1. Must be male or female between the ages of 3 and 25 years inclusive
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 defined as the presence of
any of the following:
- Nodal area >6cm OR
- Mass/thoracic diameter >one-third
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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
anatomic imaging (ie, a diagnostic CT or MRI) 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
interv period and for at least the time needed to eliminate each study
interv after the last dose of study interv. The length of time required to
continue contracep for each study intervention is:
- Pembrolizumab: no contraception requir
- Chemotherapy: refrain from donating sperm for 90 days after last dose
of chemother
PLUS either:
- Be abstinent from heterosexual intercourse as their preferred and
usual lifestyle and agree to remain abstinent
OR
- Uses contraception unless confirmed to be azoospermic documented
from the site personnel's review of the participant's medical records,
medical examination,
or medical history interview as detailed below:
o uses a male condom plus partner use of an additional contraceptive
method when having penile-vaginal intercourse with a WOCBP who is
not currently pregnant.
o Contraceptive use by men should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies.
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 uses 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), during the
intervention period and for at least the time needed to eliminate each
study intervention 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 length of
time
required to continue contraception for each study intervention is as
follows:
o Vinblastine and Vincristine: 30 days
o Other Chemotherapies: 180 days
o Pembrolizumab: 120 days. The investigator should evaluate the
potential for contraceptive method failure (ie, noncompliance, recently
initiated) in relationship to the first dose of study intervention.
Contraceptive use by women should be consistent with local
regulations regarding the methods of contraception for those
participating

Exclusion Criteria

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 24 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-PDL2
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. Received prior systemic anti-cancer therapy, including investigational
agent
6.Has received a live or live-attenuated vaccine within 30 days before
the first dose of study intervention. Administration of killed vaccines are
allowed
7. Has received an investigational agent or has used an investigational
device within 4 weeks prior to study intervention administration
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 within the past 3 years
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. An active autoimmune disease that has required systemic treatment
in past 2 years except replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid)
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 reactive) or known active Hepatitis C virus (defined as HCV RNA
[qualitative] is detected) infection
18. Has a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the study,
interfere with the participant's participation for the full duration of the
study, or is not in the best interest of the participant to participate, in
the opinion of the treating investigator
19. Has known psychiatric or substance abuse disorders that would
interfere with cooperating with the requirements of the study
20. Participants who have not adequately recovered from major surgery
or have ongoing
surgical complications.

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

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