Classical Hodgkin LymphomaEarly Phase 1NCT02981914
Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation
A Early Phase 1 study testing Pembrolizumab in people with Classical Hodgkin Lymphoma and B-cell Non-Hodgkin Lymphoma, run by University of Chicago at 1 site in United States.
Trial summary
This pilot study has been designed to investigate the safety of pembrolizumab treatment for disease relapse following allogeneic stem cell transplant (alloSCT). Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Classical Hodgkin Lymphoma, B-cell Non-Hodgkin Lymphoma, Acute Myeloid Leukemia
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2017to 1 Nov 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects with AML, MDS or mature B cell lymphomas that have relapsed following matched-related donor (MRD) or matched unrelated donor (MUD) (HLA-A -B -C -DR -DQ) alloSCT are eligible for enrollment
- Signed written informed consent
- Subjects must have signed and dated an IRB-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
- Target population
- Subjects must be ≥ 18 years of age.
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- Subjects must have an ECOG performance status of 0-1 (Appendix).
- Subjects have undergone alloSCT > 90 days prior to enrollment from a matched-related donor (MRD), matched-unrelated donor (MUD), cord blood donor, or haplo-identical and cord blood donor.
- There must be histological confirmation of relapse after alloSCT of any of the following diseases: any mature B cell lymphoma (cHL or NHL), AML or MDS.
- Subjects must be off of all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses of corticosteroids.
- Subjects with B cell lymphoma must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with CT scan. Minimum measurement must be > 15 mm in the longest diameter and > 10 mm in the short axis.
- Subjects must not have had any prior investigational agents or devices within 4 weeks of beginning study drug
- Subjects must have no prior history of VOD
- Subjects must demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of treatment initiation.
- Hematological Absolute neutrophil count (ANC) ≥ 500 /mcL Platelets ≥ 20,000 /mcL Hemoglobin ≥ 8 g/dL (RBC transfusions are OK)
- Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) or
- 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Hepatic Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5X ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN Albumin ≥ 2.0 mg/dL
- Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PT/INR should be within therapeutic range for intended use. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PTT should be within therapeutic range for intended use.
- Creatinine clearance should be calculated per institutional standard.
- Female subjects of childbearing potential should have a negative urine or serum pregnancy test (β-hCG) within 72 hours prior to receiving the first dose of study medication.
- Female subjects with childbearing potential should be willing to use 2 methods of contraception, be surgically sterile, or abstain from heterosexual activity throughout the course of the study, until 120 days after the final dose of study medication. Subjects with childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Abstinence is acceptable if this is the established and preferred contraceptive method for the subject.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study medication until 120 days after the final dose of study medicine. Abstinence is acceptable if this is the established and preferred contraceptive method for the subject.
Who cannot join
- 1. Target disease exclusions
- Subjects must not have known central nervous system involvement by disease (parenchymal, meningeal or cerebrospinal fluid) 2. Medical history, concurrent diseases, and prior treatments
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- Subjects must not have a history of any positive test for hepatitis B or hepatitis C indicating active disease or previous exposure.
- Subjects must not have a history of human immunodeficiency virus (HIV) infection.
- Subjects must not be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of study medication. The use of physiologic doses of corticosteroids is acceptable.
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- Subjects must not be concurrently receiving disease-modifying therapy in another therapeutic investigational study.
- Subjects must not have received a prior monoclonal antibody within 4 weeks prior to the first dose of study medication, and must have recovered (≤ grade 1) from adverse events related to any anti-cancer agent administered > 4 weeks previous to the first dose of study medication.
- Subjects must not have received chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study medication, and must have recovered (≤ grade 1) from adverse events related to a previously administered agent.
- Subjects must not have received a donor lymphocyte infusion (DLI) within 8 weeks prior to the first dose of study medication.
- Subjects must not have a history of severe (grade 3-4) acute GVHD, and/or current > grade 1 acute GHVD. Subjects must not have a history of chronic GVHD (whether limited or extensive stage).
- Subjects must not have 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.
- Subjects must not have a known history of congestive heart failure, unstable angina pectoris, or cardiac arrhythmia (with the exception of chronic and rate-controlled atrial fibrillation).
- Subjects must not have a history of other serious underlying medical or psychiatric condition that, in the opinion of the investigator, would impair the ability to receive, tolerate and or comply with the planned treatment and follow-up.
- Subjects must not have a history of a known secondary primary malignancy that is not in remission and/or that requires active therapy. Exceptions include non-melanoma skin cancers and in situ cervical cancer that has undergone curative-intent local therapy.
- Subjects must not have a known active infection requiring intravenous antibiotic therapy.
- Subjects must not have a history of (non-infectious) pneumonitis that required steroid treatment, evidence of interstitial lung disease, or active, non-infectious pneumonitis. Subjects must not have active, non-infectious colitis.
- Subjects must not be pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the final dose of study medication.
- Subjects must not have received a live vaccine within 30 days prior to the first dose of study medication.
- Subjects must not be or have an immediate family member (spouse, parent, legal guardian, sibling or child) who is an investigational site sponsor or staff directly involved with the trial, unless IRB approval is granted previously.
Trial locations and contacts
1 site in 1 country.
About this study
This pilot study has been designed to investigate the safety of pembrolizumab treatment for disease relapse following allogeneic stem cell transplant (alloSCT). Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Approximately 12-26 patients with relapsed MDS, AML, or mature B cell (B-NHL, cHL) malignancies that have relapsed following alloSCT will be enrolled on this trial. Pembrolizumab treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred. Adverse events will be monitored every three weeks throughout the trial and graded in severity according to the guidelines outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This trial will be conducted in accordance with Good Clinical Practices.
- Conditions
- Classical Hodgkin Lymphoma, B-cell Non-Hodgkin Lymphoma, Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- Pembrolizumab
- Keywords
- Classical Hodgkin Lymphoma, B-cell Non-Hodgkin Lymphoma, Acute Myeloid Leukemia, Myelodysplastic Syndromes, pembrolizumab
- Medical subject headings
- Lymphoma, B-Cell, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks for a max of 24 months, so long as there is no disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Dose-limiting Toxicities (DLTs)
A DLT is defined as the development of grade 3 or 4 acute GVHD (defined by the Gluckenberg scale), graft rejection, the development of any unexpected grade > 2 toxicity felt to be related to pembrolizumab, or the development of > grade 2 dysfunction of a vital organ felt to be secondary to an immune-related adverse event within 90 days following the initiation of pembrolizumab treatment.
Measured: 90 days
Secondary outcomes (3)
Time Between Initial Response and Subsequent Disease Progression or Relapse
To determine the duration of response (DOR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.
Measured: From date of response until the date of first documented progression or relapse, whichever came first, assessed up to 12 months
Objective Response Rate
For B cell lymphoma patients, partial and complete responses will be defined according to the International Working Group criteria. For MDS patients, partial and complete responses (including cytogenetic responses) will be defined according to the International Working Group criteria. Lastly, for AML patients, complete (including CR, CRp, CRi), and partial responses will be defined according to the European Leukemia Net response criteria.
Measured: 24 months
Time Between the Start of Therapy to Death From Any Cause.
Survival time in days, patients alive as of last follow-up were censored
Measured: From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study start7 Mar 2017
- Primary completion9 Oct 2020
- Study completion1 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Classical Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Justin Kline, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981914
- Sponsor's protocol ID
- IRB16-1195
- Status last verified
- Nov 2023
- First submitted
- 30 Nov 2016
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Godfrey J, Liu H, Yu J, Tallarico M, Curran E, Artz A, Riedell PA, Stock W, Karrison T, Fitzpatrick C, Venkataraman G, Cooper A, Smith SM, Bishop MR, Kline J. Pembrolizumab for the treatment of disease relapse after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2023 Mar 28;7(6):963-970. doi: 10.1182/bloodadvances.2022008403.
PubMed 35973200
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT02981914
- Acronym / sponsor ID
- IRB16-1195
- Conditions
- Classical Hodgkin Lymphoma, B-cell Non-Hodgkin Lymphoma, Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Keywords
- Classical Hodgkin Lymphoma, B-cell Non-Hodgkin Lymphoma, Acute Myeloid Leukemia, Myelodysplastic Syndromes, pembrolizumab
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 7 Mar 2017 (actual)
- Primary completion
- 9 Oct 2020 (actual)
- Study completion
- 1 Nov 2020 (actual)
- First posted
- 5 Dec 2016 (estimated)
- Results
- Posted 22 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot study has been designed to investigate the safety of pembrolizumab treatment for disease relapse following allogeneic stem cell transplant (alloSCT). Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Approximately 12-26 patients with relapsed MDS, AML, or mature B cell (B-NHL, cHL) malignancies that have relapsed following alloSCT will be enrolled on this trial. Pembrolizumab treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred. Adverse events will be monitored every three weeks throughout the trial and graded in severity according to the guidelines outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This trial will be conducted in accordance with Good Clinical Practices.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: PembrolizumabPembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Male or female subjects with AML, MDS or mature B cell lymphomas that have relapsed following matched-related donor (MRD) or matched unrelated donor (MUD) (HLA-A -B -C -DR -DQ) alloSCT are eligible for enrollment
- Hematological Absolute neutrophil count (ANC) ≥ 500 /mcL Platelets ≥ 20,000 /mcL Hemoglobin ≥ 8 g/dL (RBC transfusions are OK)
- Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) or
- Hepatic Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5X ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN Albumin ≥ 2.0 mg/dL
- Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PT/INR should be within therapeutic range for intended use. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PTT should be within therapeutic range for intended use.
Key exclusion criteria (20 listed)
- 1. Target disease exclusions
- <!-- -->
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks for a max of 24 months, so long as there is no disease progression. | Drug | Pembrolizumab |
Primary outcome
Number of Patients With Dose-limiting Toxicities (DLTs)
Time frame: 90 days
A DLT is defined as the development of grade 3 or 4 acute GVHD (defined by the Gluckenberg scale), graft rejection, the development of any unexpected grade > 2 toxicity felt to be related to pembrolizumab, or the development of > grade 2 dysfunction of a vital organ felt to be secondary to an immune-related adverse event within 90 days following the initiation of pembrolizumab treatment.
3 secondary outcomes
Time Between Initial Response and Subsequent Disease Progression or Relapse
Time frame: From date of response until the date of first documented progression or relapse, whichever came first, assessed up to 12 months
Objective Response Rate
Time frame: 24 months
Time Between the Start of Therapy to Death From Any Cause.
Time frame: From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35973200Godfrey J, Liu H, Yu J, Tallarico M, Curran E, Artz A, Riedell PA, Stock W, Karrison T, Fitzpatrick C, Venkataraman G, Cooper A, Smith SM, Bishop MR, Kline J. Pembrolizumab for the treatment of disease relapse after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2023 Mar 28;7(6):963-970. doi: 10.1182/bloodadvances.2022008403.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Justin Kline, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Pembrolizumab in people with Classical Hodgkin Lymphoma and B-cell Non-Hodgkin Lymphoma, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Dose-limiting Toxicities (DLTs) (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02981914, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024.