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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03331731




Registration number
NCT03331731
Ethics application status
Date submitted
10/10/2017
Date registered
6/11/2017
Date last updated
17/09/2020

Titles & IDs
Public title
A Phase II Study to Determine Pembrolizumab as Frontline Treatment of Patients With Hodgkin Lymphoma
Scientific title
A Multi-centre Phase II Study to Determine the Response Kinetics, Safety and Efficacy of Pembrolizumab as Frontline Treatment of Patients With Hodgkin Lymphoma Considered Unsuitable for ABVD
Secondary ID [1] 0 0
17/158
Universal Trial Number (UTN)
Trial acronym
PLIMATH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - pembrolizumab

Experimental: Single arm - Single Arm


Treatment: Drugs: pembrolizumab
Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Response using Lugano Criteria - Response will be assessed by Lugano criteria. Overall response is defined as achieving either CR or PR at any stage from time of commencement of protocol treatment to time of treatment cessation for whatever reason.
Timepoint [1] 0 0
At each treatment cycle 1 to 35 (each cycle is 3 weeks)
Secondary outcome [1] 0 0
Response using LYRIC Criteria - Response will be assessed by LYRIC criteria
Timepoint [1] 0 0
At each treatment cycle 1 to 35 (each cycle is 3 weeks)
Secondary outcome [2] 0 0
Adverse Events - Adverse Events will be evaluated using CTCAE version 4.03 as worst grade per AE
Timepoint [2] 0 0
Screening, Cycles 1-35 (each cycle is 3 weeks), end of treatment (2 years), 30 days from date of last dose, up until the first sign of progression through to study completion (3 years)
Secondary outcome [3] 0 0
Progression Free Survival (PFS) - PFS will be measured from the date of treatment commencement to the date of first progression at any site or date of death from any cause
Timepoint [3] 0 0
up until the first sign of progression through to study completion (3 years)
Secondary outcome [4] 0 0
Overal Survival (OS) - OS will be measured from the date of treatment commencement to the date death from any cause.
Timepoint [4] 0 0
up until the first sign of progression through to study completion (3 years)
Secondary outcome [5] 0 0
Treatment Intensity - Treatment intensity will be defined as the actual total dose received divided by the actual treatment period
Timepoint [5] 0 0
At each treatment cycle 1 to 35 (each cycle is 3 weeks)
Secondary outcome [6] 0 0
Event Free Survival (EFS) - EFS will be measured from the date of treatment commencement to date of documented disease progression at any site, date of commencement of next-line treatment, or date of death from any cause, whichever occurs first.
Timepoint [6] 0 0
up until the first sign of progression through to study completion (3 years)
Secondary outcome [7] 0 0
Duration of response (DoR) - DoR will be assessed on patients who responded to treatment and will be measured from the date of first documented disease response to the earliest recurrence or progressive disease. Deceased patients without recurrence or progressive disease will be censored at the last disease assessment date.
Timepoint [7] 0 0
up until the first sign of progression through to study completion (3 years)

Eligibility
Key inclusion criteria
1. Have provided written informed consent for the trial.

2. Be 18 years or greater on day of signing informed consent.

3. Have a diagnosis of Hodgkin lymphoma.

4. The patient must meet one of the following criteria:

1. Age =65

2. Considered by the investigator to be ineligible for front-line ABVD combination
chemotherapy due to reasons of medical co-morbidity

5. Have measurable disease based on the Lugano classification

6. Have stage III or IV disease; or disease stage II disease that cannot be irradiated
without unacceptable toxicity in the view of the investigator and patient.

7. Be willing to provide tissue from a "newly-obtained" core or excisional biopsy of a
tumour lesion. Newly-obtained is defined as a specimen obtained up to 8 weeks (56
days) prior to registration. Patients for whom newly-obtained samples cannot be
provided (e.g. inaccessible or patient safety concern) may submit an archived specimen
only upon agreement from the CPI.

8. Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.

9. Demonstrate adequate organ function as defined in Table 2, all screening labs should
be performed within 10 days of registration.

10. Female patient of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to registration. If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required.

11. Female patients of childbearing potential must be willing to use an adequate method of
contraception as outlined in Section 7.14 - Contraception, for the course of the study
through 120 days after the last dose of study medication.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the patient.

12. Male patients of childbearing potential must agree to use an adequate method of
contraception as outlined in Section 7.14 - Contraception, starting with the first
dose of study therapy through 120 days after the last dose of study therapy.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of registration.

2. Is receiving systemic steroid therapy or any other form of immunosuppressive therapy
within 7 days of registration. Is taking chronic systemic steroids (in doses exceeding
10 mg daily of prednisone equivalent) within 7 days prior to registration.

Note: Apart from steroids for palliative purposes specifically for lymphoma-associated
symptoms (prednisolone 50mg or equivalent for up to 10 doses) or patients with asthma
or chronic obstructive pulmonary disease that require intermittent use of
bronchodilators, inhaled steroids, or local steroid injections would not be excluded
from the study.

3. Has a known history of active TB (Bacillus Tuberculosis)

4. Hypersensitivity to pembrolizumab or any of its excipients.

5. Has had a prior anti-cancer monoclonal antibody (MoAb) within 4 weeks prior to
registration or who has not recovered (i.e., = Grade 1 at baseline) from adverse
events due to agents administered more than 4 weeks earlier.

6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks of registration or who has not recovered (i.e., = Grade 1 or at
baseline) from adverse events due to a previously administered agent.

Note: patients with = Grade 2 neuropathy are an exception to this criterion and may
qualify for the study.

Note: If a patient received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to registration.

7. Subject has a history of other active malignancies other than HL within the past 2
years prior to study entry, with the exception of:

- Adequately treated carcinoma in situ of the cervix uteri

- Adequately treated basal cell carcinoma of the skin or localized squamous cell
carcinoma of the skin, previous malignancy confined and surgically resected (or
treated with other modalities) with curative intent and less than 10% risk of
recurrence in next 12 months.

- Untreated monoclonal B lymphocytosis or chronic lymphocytic leukaemia stage 0
with <50% increase in lymphocyte count in preceding 6 months or absolute
lymphocyte count of <10 x10^9/L.

- Myelodysplastic syndrome with no excess of blasts and blood count parameters
meeting inclusion criteria, with no prior disease-modifying therapy.

- Low-risk early stage prostate adenocarcinoma (T1-T2aN0M0 and Gleason score =6 and
PSA =10ng/mL) for which the management plan is active surveillance, or prostate
adenocarcinoma with biochemical-only recurrence with documented PSA doubling time
of > 12 months for which the management plan is active surveillance

8. Has active autoimmune disease that has required systemic treatment in the 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 has current
pneumonitis.

10. Has an active infection requiring systemic therapy more than oral antibiotics.

11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient 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 pre-screening or screening visit
through 120 days after the last dose of trial treatment.

14. Has received therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent in the
preceding 12 months.

15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

17. Has received a live vaccine within 30 days of registration. Note: Seasonal influenza
vaccines for injection are generally inactivated flu vaccines and are allowed; however
intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are
not allowed.

18. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to registration and any neurologic symptoms have returned to baseline), have no
evidence of new or enlarging brain metastases, and are not using steroids for at least
7 days prior to registration. This exception does not include carcinomatous meningitis
which is excluded regardless of clinical stability.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,PerthQLD,VIC
Recruitment hospital [1] 0 0
Concord Hospital - Concord
Recruitment hospital [2] 0 0
Linear Clinical Research - Nedlands
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Alfred Health - Melbourne
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to test how safe and effective the research study drug,
pembrolizumab is as a treatment for patients with Hodgkin lymphoma who have not previously
been treated for this disease and are unsuitable for standard treatment (adriamycin,
bleomycin, vinblastine, dacarbazine ABVD).
Trial website
https://clinicaltrials.gov/show/NCT03331731
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Dickinson
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michael Dickinson
Address 0 0
Country 0 0
Phone 0 0
+61385597858
Fax 0 0
Email 0 0
Michael.Dickinson@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03331731