Relapsed Hodgkin LymphomaPhase 2NCT06484920
A Phase II Study of the Combination of Pembrolizumab and ATRA Combination Treatment of Relapsed HL and B-NHL
A Phase 2 study testing ATRA and Pembrolizumab in people with Relapsed Hodgkin Lymphoma and Refractory Hodgkin Lymphoma, run by Rita Assi at 2 sites in United States.
Trial summary
This is a Phase II single-center open label trial of the combination of ATRA and pembrolizumab treatment in patients with histologically proven, relapsed or refractory Hodgkin Lymphoma or B-Non-Hodgkin-lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma
- What is being tested?
- ATRA and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Nov 2024to Sep 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- ≥ 18 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization
- Willingness to comply with all study procedures and be available for the duration of the trial
- Have a performance status of 0 to 2 on the ECOG Performance Scale.
- Life expectancy ≥12 weeks as per investigator discretion
- Patients with histologically proven, relapsed or refractory HL or B-NHL as follows:
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- HL after failure of at least 1 prior line of systemic therapy
- Primary mediastinal large B-cell lymphoma (PMBCL) that is refractory to first-line therapy
- Other B-cell NHLs after failure of at least 2 prior lines of systemic therapy. The eligible types of B-cell NHLs are:
- Diffuse large B cell lymphoma ii. Follicular lymphoma iii. Marginal Zone lymphoma iv. Mantle Cell Lymphoma d. Indolent lymphoma are only eligible if they require systemic treatment e. Lymphocyte predominant HL are eligible Note: Formalin-fixed, paraffin embedded archival tumor sample from the primary cancer must be available for testing. If not available or sufficient, patients will be asked to undergo an US or CT guided biopsy prior to study entry to satisfy this eligibility criterion.
- Adequate hematologic and end organ function, defined by the following laboratory results obtained within 10 days prior to the first study treatment: Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) INR and aPTT ≤1.5 x ULN; this applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. Renal calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) calculated creatinine clearance ≥ 60 mL/min Hepatic Serum total bilirubin
- 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN (patients with known Gilbert disease who have bilirubin levels ≤ 3 x ULN may be enrolled). Patients must be able to undergo biliary stenting if required before or, if required, during the trial AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
- 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL
- 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. Note: Female of childbearing potential definition: (ECOG definition) Any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
- Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Refer to section 8.4.1 for more information.
- Male subjects of childbearing potential must agree to use an adequate method of contraception of the protocol, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Refer to section 8.4.1 for more information.
- Acceptable methods of contraception include IUD, oral contraceptive, subdermal implant, and double barrier (condom with a contraceptive sponge or contraceptive pessary). Micro-dosed progesterone preparations ("mini-pill") are an inadequate method of contraception during treatment with ATRA. If patients are taking this pill they should be instructed to stop, and another form of contraceptive should be prescribed instead.
- Patients with a history of CAR-T cell therapy are eligible if ≥ 3 months post treatment.
Who cannot join
- Patients 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 the first dose of treatment.
- Known brain metastases and/or leptomeningeal disease. Subjects 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 (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.
- Significant reduction in ECOG performance status between the screening/ baseline visit and within 72 hours prior to commencement of treatment as per trial protocol, as per the Investigator's assessment, defined as a reduction in ECOG score to 3 or 4.
- Patients with a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) within 7 days prior to the first dose of trial treatment.
- Note: 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.
- Hypersensitivity to pembrolizumab or any of its excipients.
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- Contraindication to the use of ATRA including but not limited to: patients with a history of hypersensitivity reaction to tretinoin, vesanoid or related compounds ( i.e. acitretin, isotretinoin, vitamin A); , Tetracyclines, Progesterone (low dose), drugs inducing P450 (rifampicin, glucocorticoids, phenobarbital, etc), ketoconazole and drugs inhibiting p450 (cimetidine, erythromycin, cyclosporine, etc); antifibrinolytic agents (e.g. tranexamic acid, aminocaproic acid, aprotinin) and hydroxyurea)
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day -1 or who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Prior chemotherapy targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day -1 or who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Subjects with chronic conditions such as vision changes or prior hearing loss that is not reasonably expected to be exacerbated by the investigational product may be included. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: Subjects with Grade 2 adrenal insufficiency or thyroid conditions who are not expected to resolve to baseline, are on a stable dose of medication may be included if it is not reasonably expected to be exacerbated by the investigational product, and asymptomatic whilst on treatment.
- History of malignancy in the last 5 years with the exception of prior history of in situ cancer or basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.
- Patient has undergone major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day -1 of treatment in this study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Known history of, or any evidence of active, non-infectious pneumonitis.
- Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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 last dose of trial treatment.
- Patients on micro-dosed progesterone preparations ("mini-pill") who are unwilling to receive an alternative form of contraception.
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- known history of active TB (Bacillus Tuberculosis).
- Receipt of live vaccine within 30 days of planned start of study therapy. 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.
- Patients who receive a COVID shot and/or booster within 4 weeks of Cycle 1 Day -1.
- Known sensitivity to retinoic acid derivatives.
- Patient is taking any prohibited concurrent medication, including Vitamin A supplements, and CYP3A modulators (inducers and inhibitors) and is unwilling to stop use (washout period of 3 days for this protocol) prior to treatment start and during the trial.
- History of allogenic stem cell transplant or received a solid organ transplant. Note: If history of transplant is ≥ 5 years, subjects may be deemed eligible at the discretion of the treating physician. Note: Patients with a history of autologous stem cell transplant performed for lymphoma are eligible.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Indiana University Health Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
Kat Ton, RN, (317) 278-8506, katton@iu.edu
Rita Assi, MD
- Recruiting
Sidney and Lois Eskenazi Hospital
Indianapolis, Indiana, 46202
Kat Ton, (317) 278-8506, katton@iu.edu
Ahmad Al-Hader
About this study
Official title: A Phase II Study of the Combination of Pembrolizumab and All-Trans Retinoic Acid Combination Treatment of Relapsed Hodgkin Lymphoma (HL) and B-Non-Hodgkin- Lymphoma (B-NHL)
This is a Phase II single-center open label trial of the combination of ATRA and pembrolizumab treatment in patients with histologically proven, relapsed or refractory Hodgkin Lymphoma or B-Non-Hodgkin-lymphoma.
- Conditions
- Relapsed Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, B-cell Lymphoma
- Being tested
- ATRA, Pembrolizumab
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATRADrug
150 mg/m2 ATRA orally for 3 days surrounding each of the first four cycles (day -1, day 0, day +1)
PembrolizumabDrug
200mg Q3W pembrolizumab
| Study group | Role | What they receive |
|---|---|---|
| ATRA and Pembrolizumab | Experimental | Patients will receive 200mg Q3W pembrolizumab treatment plus the supplemental treatment of 150 mg/m2 ATRA orally for 3 days surrounding each of the first four infusions of pembrolizumab (day -1, day 0, day +1). Receives: Drug: ATRA; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events
Safety will be assess by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Measured: from start of treatment through 90 days safety follow-up visit
Secondary outcomes (3)
Overall Response Rate
Measured: Screening to up to 2 years post last therapy
Complete Remission Rate
Measured: Screening to up to 2 years post last therapy
Patient derived myeloid-derived suppressor cells (MDSC)
Assessing the anti-tumor effect of the combination of pembrolizumab and ATRA on the reduction in myeloid-derived suppressor cells (MDSC) frequency and suppressive function through in vitro experiments using patient-derived MDSCs.
Measured: Screening, before cycle 2, before cycle 4, and within 60 days after cycle 4 day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2024
- Study start18 Nov 2024
- Primary completionDec 2027 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Hodgkin LymphomaStudies of the same condition, open and under way.
- 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
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rita Assi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rita Assi, Indiana University
- Investigators
- Rita Assi, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06484920
- Sponsor's protocol ID
- CTO-IUSCCC-0866
- Status last verified
- Feb 2026
- First submitted
- 19 Jun 2024
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Combination of Pembrolizumab and All-Trans Retinoic Acid Combination Treatment of Relapsed Hodgkin Lymphoma (HL) and B-Non-Hodgkin- Lymphoma (B-NHL)
- ClinicalTrials.gov ID
- NCT06484920
- Acronym / sponsor ID
- CTO-IUSCCC-0866
- Conditions
- Relapsed Hodgkin Lymphoma, Refractory Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, B-cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Rita AssiUniversity, hospital or other
- Study start
- 18 Nov 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 3 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II single-center open label trial of the combination of ATRA and pembrolizumab treatment in patients with histologically proven, relapsed or refractory Hodgkin Lymphoma or B-Non-Hodgkin-lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ATRA and Pembrolizumab | Experimental | Drug: ATRA, Drug: PembrolizumabPatients will receive 200mg Q3W pembrolizumab treatment plus the supplemental treatment of 150 mg/m2 ATRA orally for 3 days surrounding each of the first four infusions of pembrolizumab (day -1, day 0, day +1). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- ≥ 18 years old at the time of informed consent
- Ability to provide written informed consent and HIPAA authorization
- Willingness to comply with all study procedures and be available for the duration of the trial
- Have a performance status of 0 to 2 on the ECOG Performance Scale.
- Life expectancy ≥12 weeks as per investigator discretion
Key exclusion criteria (26 listed)
- Patients 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 the first dose of treatment.
- Known brain metastases and/or leptomeningeal disease. Subjects 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 (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.
- Significant reduction in ECOG performance status between the screening/ baseline visit and within 72 hours prior to commencement of treatment as per trial protocol, as per the Investigator's assessment, defined as a reduction in ECOG score to 3 or 4.
- Patients with a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) within 7 days prior to the first dose of trial treatment.
- Note: 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.
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 |
|---|---|---|
| ATRA150 mg/m2 ATRA orally for 3 days surrounding each of the first four cycles (day -1, day 0, day +1) | Drug | ATRA and Pembrolizumab |
| Pembrolizumab200mg Q3W pembrolizumab | Drug | ATRA and Pembrolizumab |
Primary outcome
Incidence of Adverse Events
Time frame: from start of treatment through 90 days safety follow-up visit
Safety will be assess by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
3 secondary outcomes
Overall Response Rate
Time frame: Screening to up to 2 years post last therapy
Complete Remission Rate
Time frame: Screening to up to 2 years post last therapy
Patient derived myeloid-derived suppressor cells (MDSC)
Time frame: Screening, before cycle 2, before cycle 4, and within 60 days after cycle 4 day 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2026.
- Individual participant dataSharing planned: Undecided
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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.
Rita Assi, MD principal investigator
Indiana University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATRA and Pembrolizumab in people with Relapsed Hodgkin Lymphoma and Refractory Hodgkin Lymphoma, run by Rita Assi at 2 sites 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 22 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kat Ton, RN ((317) 278-8506, katton@iu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events (time frame: from start of treatment through 90 days safety follow-up visit). 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 10 Feb 2026.