Clinical Trials /

A Phase II Study to Determine Pembrolizumab as Frontline Treatment of Patients With Hodgkin Lymphoma

NCT03331731

Description:

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).

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Study to Determine Pembrolizumab as Frontline Treatment of Patients With Hodgkin Lymphoma
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: 17/158
  • NCT ID: NCT03331731

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
pembrolizumabKeytrudaSingle arm

Purpose

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).

Detailed Description

      The study is a single arm, open label, phase II, international, multi-centre study. Sample
      size will be 25 evaluable patients with a recruitment period of 2 years. Patients will be
      administered 200mg pembrolizumab IV every 3 weeks up to 35 cycles or 2 years. Patients will
      be followed-up for 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Single armExperimentalSingle Arm
  • pembrolizumab

Eligibility Criteria

        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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response using Lugano Criteria
Time Frame:At each treatment cycle 1 to 35 (each cycle is 3 weeks)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Response using LYRIC Criteria
Time Frame:At each treatment cycle 1 to 35 (each cycle is 3 weeks)
Safety Issue:
Description:Response will be assessed by LYRIC criteria
Measure:Adverse Events
Time Frame: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)
Safety Issue:
Description:Adverse Events will be evaluated using CTCAE version 4.03 as worst grade per AE
Measure:Progression Free Survival (PFS)
Time Frame:up until the first sign of progression through to study completion (3 years)
Safety Issue:
Description: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
Measure:Overal Survival (OS)
Time Frame:up until the first sign of progression through to study completion (3 years)
Safety Issue:
Description:OS will be measured from the date of treatment commencement to the date death from any cause.
Measure:Treatment Intensity
Time Frame:At each treatment cycle 1 to 35 (each cycle is 3 weeks)
Safety Issue:
Description:Treatment intensity will be defined as the actual total dose received divided by the actual treatment period
Measure:Event Free Survival (EFS)
Time Frame:up until the first sign of progression through to study completion (3 years)
Safety Issue:
Description: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.
Measure:Duration of response (DoR)
Time Frame:up until the first sign of progression through to study completion (3 years)
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Peter MacCallum Cancer Centre, Australia

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