LymphomaPhase 2NCT06557330
MRD Guided De-intensification of Bendamustine/Rituximab for Indolent Non-Hodgkin Lymphoma
A Phase 2 study testing Bendamustine and Rituximab in people with Lymphoma and Indolent Non-hodgkin Lymphoma, run by Fox Chase Cancer Center.
Trial summary
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Lymphoma, Indolent Non-hodgkin Lymphoma
- What is being tested?
- Bendamustine and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- Jun 2025to 30 Mar 2028
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have pathologically confirmed:
- indolent Non-Hodgkin Lymphoma, consistent with one of the below diagnoses:
- Follicular Lymphoma (Grade 1-3a)
- Marginal Zone Lymphoma
- Lymphoplasmacytic Lymphoma
- Patient may be treatment naïve or relapsed/refractory without having received prior Bendamustine or patients recently started on Bendamustine 90 mg/m2 with Rituximab 375 mg/m2 are eligible if C2D1 BR is no more than 14 days prior to enrollment and they otherwise meet eligibility criteria
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- Age > 18 years
- ECOG performance status 0-2
- Patients must have normal organ and marrow function as defined below:
- Absolute Neutrophil Count >1000mm3 and Hemoglobin >8 g/dL (unless due to bone marrow involvement by lymphoma)
- Total bilirubin > 1.5x upper limit of normal (patients with Gilbert's syndrome can have total bilirubin up to 3x upper normal limit)
- Aspartate aminotransferase/ alanine aminotransferase (serum glutamic-oxaloacetic transaminase/ serum glutamic-pyruvic transaminase) < 5 times institutional normal limits
- Creatinine clearance > 30 Ml/min
Who cannot join
- Radiation or systemic treatment for lymphoma within the past 28 days prior to cycle 1 day 1 of BR.
- Patients with pathologically confirmed transformed lymphoma, including diffuse large B cell lymphoma or other high grade lymphomas
- Patients on active treatment for second malignancy with the exception of endocrine therapy for non-metastatic breast cancer, hormone therapy for prostate cancer, or local treatment for non-melanoma skin cancer.
- Pregnant or breast-feeding. Refer to section 5.4 for further detail.
- Failure to identify a dominant clonal sequence with ClonoSEQ from pre-treatment specimen or inadequate tissue for testing
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: HM-225: Measurable Residual Disease (MRD) Guided De-intensification of Bendamustine/Rituximab (BR) for Indolent Non-Hodgkin Lymphoma
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.
Read the detailed description
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.
All patients with untreated or R/R (not previously treated with Bendamustine) iNHL (Follicular Lymphoma (Grade 1-3a2), Marginal Zone Lymphoma, Lymphoplasmacytic Lymphoma) are candidates for this trial. Patients requiring treatment per treating physician's discretion are eligible for the trial.
Patients who recently started on and received two cycles of Bendamustine at 90 mg/m2 dose with Ritxumab 375 mg/m2 are also eligible for this trial. For these patients, C2D1 BR should be no more than 14 days prior to the time of study enrollment (i.e. enrollment no later than C2D14). Patients who have received two cycles of 90mg/m2 Bendamustine dose with Rituximab 375 mg/m2 can enter the study and initiate cycle 3 once pre-screening and screening procedures have been completed.
- Conditions
- Lymphoma, Indolent Non-hodgkin Lymphoma
- Being tested
- Bendamustine, Rituximab
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Also called cytostasan, belrapzo, treanda, vivimusta
Bendamustine will be administered as 10 minute IV infusion at 90 mg/m2 (drug dose calculation is based on treatment day weight) on days 1 and 2 for 4-6 cycles (number of cycles determined per treatment design). Subjects will be dosed every 28 days. Ondansetron 16 mg IV is given as premedication per institutional guidelines. Dose modifications will be determined based on renal and hepatic function. Subjects should be carefully monitored for infusion reactions during Bendamustine administration. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Bendamustine may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment based on physician discretion.
RituximabDrug
Also called riabni, Rituxan, Ruxience, Truxima
Rituximab will be administered as an IV infusion at 375 mg/m2 (longer for the first dose) (drug dose calculation is based of treatment day weight) on day 1 for 4-6 cycles (number of cycles determined per treatment design). Infusion rate will be determined as per institutional standards. Subjects will be dosed every 28 days. Diphenhydramine 50 mg IV and acetaminophen 650 mg are required to be given to the subjects within 30 minutes prior to Rituximab dose. There are no dose modifications recommended with Rituximab. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Rituximab may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of Measurable Residual Disease (MRD) adapted duration of BR for untreated or R/R iNHL (indolent non-hodgkin lymphoma). All patients will receive Bendamustine 90 mg/m2 IV on Days 1-2 and Rituximab 375 mg/m2 IV(BR) on Day 1 of each cycle. Each cycle will last 28 days. On day 1 of each cycle, patients will receive Rituximab before Bendamustine, and CBC (complete blood count), CMP (comprehensive metabolic panel) will be obtained to capture any hematologic toxicities as well as clonoSEQ testing to determine MRD status. After completing Cycle 3, imaging results (with confirmatory biopsy if applicable) and the clonoSEQ MRD testing results obtained from ctDNA (blood collection) will determine whether patients will receive Cycles 5 and 6 of Bendamustine and Rituximab (BR). Receives: Drug: Bendamustine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS Evaluation
To evaluate the 2-year progression free survival (PFS) for patients treated with Bendamustine and Rituximab (BR) with measurable residual disease directed (MRD) duration of therapy.
Measured: 2 years
Statistical PFS
The proportion (p) of patients who are progression-free and are alive at 2 years from the initiation of treatment using Lugano Criteria.
Measured: 2 years
Secondary outcomes (6)
Secondary Outcome Measure
Assess additional clinical outcomes including overall survival (OS),
Measured: 2 years
Measurable Residual Disease Evaluation
To determine the rate of MRD (minimal residual disease) negativity at end of treatment and at 2 years post-treatment
Measured: 2 years
Adverse Event assessment
Assess adverse effects of treatment
Measured: 2 years
Overall Survival Assessment
OS, defined as time from initiation of study treatment until death, or the end of follow-up, whichever occurs first. Patients who are still alive at the end of follow-up will be considered censored.
Measured: 2 years
Measurable Residual Disease Negativity
To evaluate MRD negativity rate at the end of treatment and at 2 years post-treatment.
Measured: 2 years
Rate of 3+ adverse events
The rate of grade 3+ adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.The rate of grade 3+ adverse events as assessed by CTCAE v5.0.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2024
- Study startJun 2025 (estimated)
- Primary completion29 Sep 2027 (estimated)
- Study completion30 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Adaptive Biotechnologies
- Responsible party
- Sponsor
- Investigators
- Marcus Messmer, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06557330
- Sponsor's protocol ID
- 24-1014, HM-225
- Status last verified
- Jan 2025
- First submitted
- 9 Aug 2024
- Last updated
- 6 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HM-225: Measurable Residual Disease (MRD) Guided De-intensification of Bendamustine/Rituximab (BR) for Indolent Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT06557330
- Acronym / sponsor ID
- 24-1014, HM-225
- Conditions
- Lymphoma, Indolent Non-hodgkin Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- Adaptive Biotechnologies
- Study start
- Jun 2025 (estimated)
- Primary completion
- 29 Sep 2027 (estimated)
- Study completion
- 30 Mar 2028 (estimated)
- First posted
- 16 Aug 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 pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.
Detailed description
This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.
All patients with untreated or R/R (not previously treated with Bendamustine) iNHL (Follicular Lymphoma (Grade 1-3a2), Marginal Zone Lymphoma, Lymphoplasmacytic Lymphoma) are candidates for this trial. Patients requiring treatment per treating physician's discretion are eligible for the trial.
Patients who recently started on and received two cycles of Bendamustine at 90 mg/m2 dose with Ritxumab 375 mg/m2 are also eligible for this trial. For these patients, C2D1 BR should be no more than 14 days prior to the time of study enrollment (i.e. enrollment no later than C2D14). Patients who have received two cycles of 90mg/m2 Bendamustine dose with Rituximab 375 mg/m2 can enter the study and initiate cycle 3 once pre-screening and screening procedures have been completed.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Bendamustine, Drug: RituximabThis is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of Measurable Residual Disease (MRD) adapted duration of BR for untreated or R/R iNHL (indolent non-hodgkin lymphoma). All patients will receive Bendamustine 90 mg/m2 IV on Days 1-2 and Rituximab 375 mg/m2 IV(BR) on Day 1 of each cycle. Each cycle will last 28 days. On day 1 of each cycle, patients will receive Rituximab before Bendamustine, and CBC (complete blood count), CMP (comprehensive metabolic panel) will be obtained to capture any hematologic toxicities as well as clonoSEQ testing to determine MRD status. After completing Cycle 3, imaging results (with confirmatory biopsy if applicable) and the clonoSEQ MRD testing results obtained from ctDNA (blood collection) will determine whether patients will receive Cycles 5 and 6 of Bendamustine and Rituximab (BR). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- indolent Non-Hodgkin Lymphoma, consistent with one of the below diagnoses:
- Follicular Lymphoma (Grade 1-3a)
- Marginal Zone Lymphoma
- Lymphoplasmacytic Lymphoma
- Patient may be treatment naïve or relapsed/refractory without having received prior Bendamustine or patients recently started on Bendamustine 90 mg/m2 with Rituximab 375 mg/m2 are eligible if C2D1 BR is no more than 14 days prior to enrollment and they otherwise meet eligibility criteria
Key exclusion criteria (5 listed)
- Radiation or systemic treatment for lymphoma within the past 28 days prior to cycle 1 day 1 of BR.
- Patients with pathologically confirmed transformed lymphoma, including diffuse large B cell lymphoma or other high grade lymphomas
- Patients on active treatment for second malignancy with the exception of endocrine therapy for non-metastatic breast cancer, hormone therapy for prostate cancer, or local treatment for non-melanoma skin cancer.
- Pregnant or breast-feeding. Refer to section 5.4 for further detail.
- Failure to identify a dominant clonal sequence with ClonoSEQ from pre-treatment specimen or inadequate tissue for testing
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 |
|---|---|---|
| BendamustineAlso: cytostasan, belrapzo, treanda, vivimustaBendamustine will be administered as 10 minute IV infusion at 90 mg/m2 (drug dose calculation is based on treatment day weight) on days 1 and 2 for 4-6 cycles (number of cycles determined per treatment design). Subjects will be dosed every 28 days. Ondansetron 16 mg IV is given as premedication per institutional guidelines. Dose modifications will be determined based on renal and hepatic function. Subjects should be carefully monitored for infusion reactions during Bendamustine administration. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Bendamustine may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment based on physician discretion. | Drug | Single Arm |
| RituximabAlso: riabni, Rituxan, Ruxience, TruximaRituximab will be administered as an IV infusion at 375 mg/m2 (longer for the first dose) (drug dose calculation is based of treatment day weight) on day 1 for 4-6 cycles (number of cycles determined per treatment design). Infusion rate will be determined as per institutional standards. Subjects will be dosed every 28 days. Diphenhydramine 50 mg IV and acetaminophen 650 mg are required to be given to the subjects within 30 minutes prior to Rituximab dose. There are no dose modifications recommended with Rituximab. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Rituximab may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment. | Drug | Single Arm |
Primary outcome
PFS Evaluation
Time frame: 2 years
To evaluate the 2-year progression free survival (PFS) for patients treated with Bendamustine and Rituximab (BR) with measurable residual disease directed (MRD) duration of therapy.
Statistical PFS
Time frame: 2 years
The proportion (p) of patients who are progression-free and are alive at 2 years from the initiation of treatment using Lugano Criteria.
6 secondary outcomes
Secondary Outcome Measure
Time frame: 2 years
Measurable Residual Disease Evaluation
Time frame: 2 years
Adverse Event assessment
Time frame: 2 years
Overall Survival Assessment
Time frame: 2 years
Measurable Residual Disease Negativity
Time frame: 2 years
Rate of 3+ adverse events
Time frame: 2 years
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 6 Jan 2025.
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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.
Marcus Messmer principal investigator
Fox Chase Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bendamustine and Rituximab in people with Lymphoma and Indolent Non-hodgkin Lymphoma, run by Fox Chase Cancer Center.
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 13 inclusion and 5 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: opening soon, as of the sponsor's last update on 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
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 Abigail O'Keefe (215-728-2451, abigail.o'keefe@fccc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS Evaluation (time frame: 2 years). The study lists 2 primary outcomes in all. 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 6 Jan 2025.