Hodgkin's LymphomaPhase 2NCT03776864
Umbralisib and Pembrolizumab in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
A Phase 2 study testing Pembrolizumab and Umbralisib in people with Hodgkin's Lymphoma, run by University of Washington at 1 site in United States.
Trial summary
This phase II trial studies how well umbralisib and pembrolizumab work in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin's Lymphoma
- What is being tested?
- Pembrolizumab and Umbralisib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2019to 14 Sep 2021
- Phase
- Phase 2
- 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
- Relapsed or refractory CHL that has received at least 1 prior lines of therapy
- Measurable fludeoxyglucose F-18 (FDG)-avid disease defined by standard criteria (Lugano 2014) and a minimum of 1.0 cm in diameter
- Prior treatment with anti-PD1 or anti-PDL1 therapy is allowed.
- Patients who are currently on anti-PD1 or anti-PDL1 therapy who have failed to achieve a CR after at least 18 weeks of treatment may enroll on study. For these patients, anti-PD1 or anti-PDL1 therapy may be delayed for screening and to align pembrolizumab dosing with the expected cycle 1 day 1. Patients with progressive disease after prior anti-PD1 or anti-PDL1 therapy do not have to be treated for 18 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Ability to swallow and retain oral medication
Show all 16Show fewer
- Willingness and ability to comply with study and follow-up procedures, and give written informed consent
- Female subjects of childbearing potential must be surgically sterile, be post-menopausal (for at least 1 year prior to screening visit), or must have a negative pregnancy test within 3 days prior to cycle 1 day 1 and agree to use medically acceptable contraception throughout the study period and for 4 months after the last dose of either study drug. Men of reproductive potential may not participate unless they agree to use medically acceptable contraception throughout the study period and for 4 months after the last dose of either study drug
- Patients must be expected to receive at least 2 cycles of therapy
- Patients should have a life expectancy if untreated of >= 90 days in the opinion of the investigator
- Patients must have a FDG-positron emission tomography (PET)-computed tomography (CT) of chest, abdomen, and pelvis within 42 days of enrollment
- Absolute neutrophil count (ANC) > 750
- Platelet count > 40,000
- Total bilirubin =< 1.5 times the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (if known liver involvement then =< 5 x ULN is allowed)
- Calculated creatinine clearance > 30 mL/min (as calculated by the Cockcroft-Gault formula)
Who cannot join
- Patients receiving cancer therapy (i.e., chemotherapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization, prednisone > 10 mg or equivalent) or any investigational drug within 21 days of cycle 1 day 1. Patients receiving radiation therapy within 14 days from cycle 1 day 1. Anti-PD1 or anti-PDL1 therapy in patients with less than a CR after 18 weeks of such therapy is permitted to continue on schedule
- Discontinuation from prior anti-PD1 or anti-PDL1 therapy due to immune-related adverse event or any other treatment-related adverse event
- Autologous transplantation within 100 days
- Prior allogeneic transplant within 12 months of initiation on study
- Active graft versus host disease (GVHD) within 90 days prior to cycle 1 day 1
- Evidence of active central nervous system lymphoma
Show all 17Show fewer
- Pregnant or nursing women
- Evidence of chronic active hepatitis B or chronic active hepatitis C infection (hepatitis C virus [HCV]), active cytomegalovirus (CMV), or known history of human immunodeficiency virus (HIV). If hepatitis B core (HBc) antibody, HCV antibody or CMV immunoglobulin (Ig)M is positive, the patient should be correspondingly evaluated for the presence of HBV, HCV or CMV by deoxyribonucleic acid (DNA) (polymerase chain reaction [PCR]) to determine presence or absence of active infection. If HBc antibody is positive, the subject must be evaluated for the presence of hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR). If HCV antibody is positive, the subject must be evaluated for the presence of HCV ribonucleic acid (RNA) by PCR. Subjects with positive HBc antibody and negative HBV DNA by PCR are eligible. Subjects with positive HCV antibody and negative HCV RNA by PCR are eligible. Subjects who are cytomegalovirus (CMV) IgG or CMV IgM positive but who are CMV DNA negative by PCR are eligible
- Prior exposure to idelalisib (CAL-101), duvelisib (IPI-145), or any drug that specifically inhibits phosphoinositide-3-kinase (PI3K)
- Evidence of ongoing active systemic bacterial, fungal or viral infection
- Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic, or history of documented congestive heart failure (New York [NY] Heart Association functional classification III-IV)
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of randomization
- Concomitant use of medication known to cause QT prolongation or torsades de pointes. Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within 3 months of randomization
- Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol principal investigator
- Patients with an active autoimmune disorder (with the exception of autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura [ITP] or vitiligo)
- History of non-infectious pneumonitis related to prior line of therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: A Phase II Trial of Umbralisib and Pembrolizumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
This phase II trial studies how well umbralisib and pembrolizumab work in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving umbralisib and pembrolizumab may work better in treating classical Hodgkin lymphoma.
Read the detailed description
OUTLINE:
Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib orally (PO) daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days, then up to 1 year.
- Conditions
- Hodgkin's Lymphoma
- Being tested
- Pembrolizumab, Umbralisib
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called Immunoglobulin G4, Anti-(Human Programmed Cell Death 1), Lambrolizumab, MK-3475
Given IV
UmbralisibDrug
Also called TGR-1202, RP5264
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab, umbralisib) | Experimental | Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Pembrolizumab; Drug: Umbralisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate
Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve a complete response (CR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass.
Measured: Up to 1 year
Secondary outcomes (2)
Overall Response Rate
Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve an overall response (OR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass; Partial Metabolic Response, Deauville score of 4 or 5 with reduced uptake compared to baseline and residual mass(es) of any size; No Response or Stable Disease, Deauville score of 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatment.
Measured: Up to 1 year
Number of Participants With Adverse Events
Measured via CTCAE v4.0. Incidence of adverse events is defined as the count of participants who experienced an adverse event.
Measured: Up to 28 days post-treatment, approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2018
- Study start26 Sep 2019
- Primary completion14 Sep 2021
- Study completion14 Sep 2021
Why it stopped: Company providing drug terminated their oncology program
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.
- Other trials for Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- TG Therapeutics, Inc.
- Responsible party
- Principal investigator, Ryan Lynch, University of Washington
- Investigators
- Ryan Lynch, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03776864
- Sponsor's protocol ID
- RG1003718
- Other IDs
- NCI-2018-02836, 10075
- Status last verified
- Apr 2023
- First submitted
- 13 Dec 2018
- Last updated
- 3 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Umbralisib and Pembrolizumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT03776864
- Acronym / sponsor ID
- RG1003718
- Conditions
- Hodgkin's Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company providing drug terminated their oncology program
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- TG Therapeutics, Inc.
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 14 Sep 2021 (actual)
- Study completion
- 14 Sep 2021 (actual)
- First posted
- 17 Dec 2018 (actual)
- Results
- Posted 3 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well umbralisib and pembrolizumab work in treating patients with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving umbralisib and pembrolizumab may work better in treating classical Hodgkin lymphoma.
Detailed description
OUTLINE:
Patients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib orally (PO) daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days, then up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pembrolizumab, umbralisib) | Experimental | Biological: Pembrolizumab, Drug: UmbralisibPatients receive pembrolizumab IV on day 1. Treatment repeats every 21 for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive umbralisib PO daily on days 1-21 days. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Relapsed or refractory CHL that has received at least 1 prior lines of therapy
- Measurable fludeoxyglucose F-18 (FDG)-avid disease defined by standard criteria (Lugano 2014) and a minimum of 1.0 cm in diameter
- Prior treatment with anti-PD1 or anti-PDL1 therapy is allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Ability to swallow and retain oral medication
Key exclusion criteria (17 listed)
- Patients receiving cancer therapy (i.e., chemotherapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization, prednisone > 10 mg or equivalent) or any investigational drug within 21 days of cycle 1 day 1. Patients receiving radiation therapy within 14 days from cycle 1 day 1. Anti-PD1 or anti-PDL1 therapy in patients with less than a CR after 18 weeks of such therapy is permitted to continue on schedule
- Discontinuation from prior anti-PD1 or anti-PDL1 therapy due to immune-related adverse event or any other treatment-related adverse event
- Autologous transplantation within 100 days
- Prior allogeneic transplant within 12 months of initiation on study
- Active graft versus host disease (GVHD) within 90 days prior to cycle 1 day 1
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 |
|---|---|---|
| PembrolizumabAlso: Immunoglobulin G4, Anti-(Human Programmed Cell Death 1), Lambrolizumab, MK-3475Given IV | Biological | Treatment (pembrolizumab, umbralisib) |
| UmbralisibAlso: TGR-1202, RP5264Given PO | Drug | Treatment (pembrolizumab, umbralisib) |
Primary outcome
Complete Response Rate
Time frame: Up to 1 year
Proportion of subjects with relapsed/ refractory classical Hodgkin Lymphoma (CHL) who achieve a complete response (CR) with a regimen of umbralisib (oral, daily) and pembrolizumab (IV, day 1 of 21-day cycles). Per Response Evaluation Criteria Lugano 2014 for target lesions and assessed by PET-CT, Complete Metabolic Response (CMR), Deaville score of 1, 2, or 3 in nodal or extranodal sites with or without residual mass.
2 secondary outcomes
Overall Response Rate
Time frame: Up to 1 year
Number of Participants With Adverse Events
Time frame: Up to 28 days post-treatment, approximately 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Hodgkin's Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
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.
Ryan Lynch principal investigator
Fred Hutch/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Umbralisib in people with Hodgkin's Lymphoma, run by University of Washington 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 16 inclusion and 17 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: stopped early, as of the sponsor's last update on 3 May 2023. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 May 2023). 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?
Complete Response Rate (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 May 2023.