Clinical Trials /

Pembrolizumab and Involved Site Radiation Therapy for Early Stage Relapsed or Primary Refractory Hodgkin Lymphoma

NCT03179917

Description:

This study is being done to test the safety and effectiveness of pembrolizumab followed by radiation therapy in Hodgkin lymphoma. The purpose of this study is to determine how effective combining the research drug, pembrolizumab, with a targeted form of radiation therapy known as involved site radiotherapy can be in patients with relapsed or refractory early stage classical Hodgkin lymphoma. The goal is to see whether this treatment strategy can cure a significant number of patients with relapsed or refractory early stage classical Hodgkin lymphoma while avoiding the toxicity of either a large radiation field or further chemotherapy and stem cell transplant.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Involved Site Radiation Therapy for Early Stage Relapsed or Primary Refractory Hodgkin Lymphoma
  • Official Title: Pembrolizumab and Involved Site Radiation Therapy for Early Stage Relapsed or Primary Refractory Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 17-054
  • NCT ID: NCT03179917

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab and Involved Site Radiation Therapy

Purpose

This study is being done to test the safety and effectiveness of pembrolizumab followed by radiation therapy in Hodgkin lymphoma. The purpose of this study is to determine how effective combining the research drug, pembrolizumab, with a targeted form of radiation therapy known as involved site radiotherapy can be in patients with relapsed or refractory early stage classical Hodgkin lymphoma. The goal is to see whether this treatment strategy can cure a significant number of patients with relapsed or refractory early stage classical Hodgkin lymphoma while avoiding the toxicity of either a large radiation field or further chemotherapy and stem cell transplant.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab and Involved Site Radiation TherapyExperimentalFollowing a PET/CT simulation to evaluate the extent of disease, pembrolizumab 200mg IV will be given over 30 minutes on day 1 of each 21 day cycle for a total of 4 cycles. Fourteen to 21 days after the completion of therapy, a PET/CT simulation will be repeated. Pts with complete response will proceed to 20 Gy of ISRT. Pts without a PET CR, but improvement on CT scan will have a repeat biopsy. If the biopsy is negative for Hodgkin Lymphoma, these ps will receive 30 Gy of ISRT. If the biopsy is positive for Hodgkin Lymphoma, they will receive 36-40 Gy ISRT. Pts without a PET CR, but improvement on CT scan will have a repeat biopsy. If the biopsy is negative for Hodgkin Lymphoma, these pts will receive 30 Gy of ISRT. If the biopsy is positive for Hodgkin Lymphoma, they will receive 36-40 Gy ISRT. Pts with new sites of disease or progression on imaging will have a repeat biopsy, per treating physician's discretion & then be treated off study.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Three populations of patients are eligible for enrollment:

             (1) Patients with early stage disease at diagnosis (stage I-II) who were treated with
             chemotherapy alone and relapsed with early stage disease (stage RI-II).

             (2) Patients with early stage disease at diagnosis (stage I-II) who were treated with
             chemotherapy alone and have early stage (stage RI-II) primary refractory disease
             (residual disease on a scan 1 month after the completion of initial therapy) without
             B-symptoms and with each area of disease less than 10 cm in size.

             (3) Patients with early stage disease at diagnosis (stage I-II) who were treated with
             combined modality therapy (chemotherapy and radiation) who relapse with early stage
             disease (stage RI-II) outside the prior radiation therapy field.

          -  Histologic confirmation of classical Hodgkin Lymphoma after imaging documenting
             primary refractory or relapsed disease

          -  Age 18 or older

          -  ECOG Performance Status of 0-1

          -  Adequate organ function. Screening labs should be performed within 14 days of
             treatment initiation.

        Hematologic

          -  Absolute neutrophil count (ANC) ≥1,000 /mcL

          -  Platelets* ≥75,000 / mcL

          -  Hemoglobin* ≥8 g/dL Renal

          -  Creatinine OR Measured or calculated** creatinine clearance CrCl (GFR can also be used
             in place of creatinine or ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject
             with creatinine levels > 1.5 X institutional ULN Hepatic

          -  Total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total
             bilirubin levels >1.5 ULN

          -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver involvement
             Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated
             Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving
             anticoagulant therapy, then as long as PT or PTT is within therapeutic range of
             intended use of anticoagulants

               -  1.5 X ULN unless subject is receiving anticoagulant therapy, then as long as PT
                  or PTT is within therapeutic range of intended use of anticoagulants * Hemoglobin
                  and platelet requirements cannot be met by use of recent transfusion or growth
                  factor support (GCSF or erythropoietin) within 2 weeks prior to treatment
                  initiation.

                    -  Creatinine clearance should be calculated per institutional standard.

                         -  Female subject of childbearing potential should have a negative urine
                            or serum pregnancy within 72 hours prior to receiving the first dose of
                            study medication. If the urine test is positive or cannot be confirmed
                            as negative, a serum pregnancy test will be required.

        Female subjects of childbearing potential should be willing to use 2 methods of birth
        control or be surgically sterile, or abstain from sexual activity for the course of the
        study through 120 days after the last dose of study medication (Reference Section 5.7.2).
        Subjects of child bearing potential are those who have not been surgically sterilized or
        have not been free from menses for > 1 year.

        Note: Abstinence is acceptable if this is the established and preferred contraception for
        the subject.

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.

        Note: Abstinence is acceptable if this is the established and preferred contraception for
        the subject.

        Exclusion Criteria:

          -  Ann Arbor Stage III or IV disease at diagnosis or at relapse/refractory disease
             confirmation.

          -  Bulky disease (>10cm) at diagnosis or at relapse/refractory disease confirmation.

          -  Active B symptoms.

          -  Received >1 line of therapy for Hodgkin lymphoma

          -  Relapsed/refractory disease within a prior radiation field.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             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 a previously administered agent.

          -  Diagnosis of immunosuppression or is receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment. The use of physiologic doses of corticosteroids may be approved after
             consultation with the Sponsor.

          -  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 in situ cervical cancer that has undergone potentially curative therapy.

          -  Has 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

          -  Has history of (non-infectious) pneumonitis that required steroids, evidence of
             interstitial lung disease or active, non infectious pneumonitis

          -  Has an active infection requiring intravenous systemic therapy.

          -  Has a known Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C
             (HCV) infection

          -  Has received a live vaccine within 30 days prior to first dose

          -  Any other medical condition or laboratory evaluation that, in the treating physician's
             or principal investigator's opinion, makes the patient unsuitable to participate in
             this clinical trial

          -  Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
             recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Has had treatment a prior monoclonal antibody targeting PD-1, PD-L1, PD-L2, or CTLA-4.

          -  Has a pre-treatment TTE showing a calculated left ventricular ejection fraction of
             less than 50%

          -  Has a pre-treatment PFT showing an DLCO adjusted for hemoglobin of less than 60%

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

Primary Outcome Measures

Measure:complete response rate
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Pembrolizumab
  • Radiation Therapy
  • 17-054

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