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RADVAX™ for Relapsed/Refractory Non-Hodgkin Lymphoma: A Phase II Trial of Pembrolizumab + Low Dose Radiotherapy

Primary Purpose

Non Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Sponsored by
Abramson Cancer Center at Penn Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Hodgkin Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of relapsed/refractory non-Hodgkin lymphoma (defined below) will be enrolled in this study.

Male participants:

- A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.

Female participants:

  • A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
    2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of treatment initiation.
  • Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.
  • Pathologically confirmed B-cell, T-cell, aggressive, or indolent non-Hodgkin lymphoma for whom pembrolizumab is clinically indicated per physician discretion.
  • Relapsed/refractory disease treated with at least 2 lines of prior therapy.

    • Relapsed disease is defined as progression of disease after achieving a remission to the most recent therapy.
    • Refractory disease is defined as failure to achieve CR or PR.
    • At least 2 lines of prior therapy are required, but, at physician and patient discretion with shared decision making, not all FDA-approved treatments need be exhausted prior to enrollment.
  • For DLBCL and PMBCL:

    • Have relapsed after auto-SCT or have failed to achieve a CR or PR within 60 days of auto-SCT. Patients may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment.
    • For patients who are ineligible for auto-SCT, have received at least ≥ 2 lines of prior therapy and have failed to respond to or relapsed after their last line of treatment. For patients who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of treatment.
  • Prior chimeric antigen receptor T-cell (CART) therapy is allowed but not required.

    • If the patient has received CART therapy, complete resolution of any active cytokine release syndrome is required 13. ≥2 sites of measurable disease (≥1.0 cm), at least one outside of intended RT fields.

      14. Ability to provide written informed consent.

Exclusion Criteria:

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to treatment initiation.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • 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.
  • Has a diagnosis of immunodeficiency or is 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 study drug.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 1 year.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Has undergone allogeneic bone marrow transplantation within 5 years.
  • History of graft-versus-host-disease.
  • Has a known history of Human Immunodeficiency Virus (HIV).
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.

Sites / Locations

  • Abamson Cancer Center of the University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab and Radiation Therapy

Arm Description

pembrolizumab plus low-dose (4 Gy x 5) involved-site radiotherapy

Outcomes

Primary Outcome Measures

CR rate

Secondary Outcome Measures

Time to best response
Duration of best response
Progression-free survival (PFS)
Overall survival
Duration of immunotherapy use for the pembrolizumab + RT induction CR cohort

Full Information

First Posted
March 30, 2021
Last Updated
January 9, 2023
Sponsor
Abramson Cancer Center at Penn Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT04827862
Brief Title
RADVAX™ for Relapsed/Refractory Non-Hodgkin Lymphoma: A Phase II Trial of Pembrolizumab + Low Dose Radiotherapy
Official Title
RADVAX™ for Relapsed/Refractory Non-Hodgkin Lymphoma: A Phase II Trial of Pembrolizumab + Low Dose Radiotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is an open-label Phase II trial of non-Hodgkin lymphoma patients receiving initial treatment with the immunomodulatory agent, pembrolizumab, plus low-dose (4 Gy x 5) involved-site radiotherapy. Eligible patients will have r/r disease with at least 2 sites of measurable disease (≥1.0 cm), and must be eligible for treatment with pembrolizumab. Biosamples (blood and, where available, tumor) will be collected as outlined below. Pembrolizumab will be continued after RT until disease progression, drug intolerance, or at the discretion of the treating medical oncologist.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab and Radiation Therapy
Arm Type
Experimental
Arm Description
pembrolizumab plus low-dose (4 Gy x 5) involved-site radiotherapy
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
pembrolizumab plus low-dose (4 Gy x 5) involved-site radiotherapy
Primary Outcome Measure Information:
Title
CR rate
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Time to best response
Time Frame
20 weeks
Title
Duration of best response
Time Frame
5 years
Title
Progression-free survival (PFS)
Time Frame
5 years
Title
Overall survival
Time Frame
5 years
Title
Duration of immunotherapy use for the pembrolizumab + RT induction CR cohort
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of relapsed/refractory non-Hodgkin lymphoma (defined below) will be enrolled in this study. Male participants: - A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of treatment initiation. Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment. Pathologically confirmed B-cell, T-cell, aggressive, or indolent non-Hodgkin lymphoma for whom pembrolizumab is clinically indicated per physician discretion. Relapsed/refractory disease treated with at least 2 lines of prior therapy. Relapsed disease is defined as progression of disease after achieving a remission to the most recent therapy. Refractory disease is defined as failure to achieve CR or PR. At least 2 lines of prior therapy are required, but, at physician and patient discretion with shared decision making, not all FDA-approved treatments need be exhausted prior to enrollment. For DLBCL and PMBCL: Have relapsed after auto-SCT or have failed to achieve a CR or PR within 60 days of auto-SCT. Patients may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment. For patients who are ineligible for auto-SCT, have received at least ≥ 2 lines of prior therapy and have failed to respond to or relapsed after their last line of treatment. For patients who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of treatment. Prior chimeric antigen receptor T-cell (CART) therapy is allowed but not required. If the patient has received CART therapy, complete resolution of any active cytokine release syndrome is required 13. ≥2 sites of measurable disease (≥1.0 cm), at least one outside of intended RT fields. 14. Ability to provide written informed consent. Exclusion Criteria: A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment initiation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to treatment initiation. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 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. Has a diagnosis of immunodeficiency or is 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 study drug. Has a known additional malignancy that is progressing or has required active treatment within the past 1 year. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Has an active infection requiring systemic therapy. Has a known history of active TB (Bacillus Tuberculosis). Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. Has undergone allogeneic bone marrow transplantation within 5 years. History of graft-versus-host-disease. Has a known history of Human Immunodeficiency Virus (HIV). Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kathy Ransone
Phone
215-662-4726
Email
kathy.ransone@uphs.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Plastaras, MD, PhD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abamson Cancer Center of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Plastaras, MD, PhD
Phone
855-216-0098
Email
john.plastaras2@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
John Plastaras, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

RADVAX™ for Relapsed/Refractory Non-Hodgkin Lymphoma: A Phase II Trial of Pembrolizumab + Low Dose Radiotherapy

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