RBM Regimen for Multiple Myeloma and Lymphoma

Overseen By Paul Hamlin, MD

Age: 65+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: CNS involvement, Prior transplant, MI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments called RBM for effectiveness in people with certain blood cancers, such as multiple myeloma and B-cell lymphoma. RBM combines rituximab (an immunotherapy), bendamustine (a chemotherapy drug), and melphalan (another chemotherapy drug), followed by autologous stem cell transplantation (ASCT). Researchers aim for this combination to cause fewer side effects than standard treatments. Individuals with multiple myeloma or specific forms of lymphoma, like DLBCL, may be suitable candidates, especially if they have responded to previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I need to stop my current medications for the RBM trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the RBM treatment, which includes rituximab, bendamustine, and melphalan, is safe for individuals with certain blood cancers. One study found that administering bendamustine and melphalan before a stem cell transplant in older patients with non-Hodgkin lymphoma or multiple myeloma was safe and had few side effects. Patients reported tolerating the treatment well. Compared to the standard BEAM treatment, the RBM treatment may have fewer side effects, potentially making it easier on the body. Although this treatment is still under investigation, early results are promising for those concerned about harsh side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the RBM regimen for treating certain blood cancers because it combines rituximab, bendamustine, and melphalan, followed by an autologous stem cell transplant, offering a potentially powerful treatment for elderly patients with B-cell non-Hodgkin lymphoma (NHL). Unlike standard treatments which often rely on single or dual-drug regimens, this approach uses a three-drug combination that targets cancer cells more aggressively. Rituximab specifically targets CD20 proteins on B-cells, bendamustine disrupts the DNA in cancer cells, and melphalan further damages cancer cell DNA, leading to more effective tumor reduction. This multi-faceted attack, followed by stem cell support, could provide a more effective and robust solution for patients who may not respond well to conventional therapies.

What evidence suggests that the RBM regimen could be an effective treatment for multiple myeloma and lymphoma?

Research has shown that combining rituximab, bendamustine, and melphalan (RBM) with autologous stem cell transplantation (ASCT) may effectively treat multiple myeloma and lymphoma. In this trial, participants will receive the RBM regimen followed by ASCT. Studies indicate that bendamustine and melphalan are safe, with manageable side effects for patients with non-Hodgkin lymphoma and multiple myeloma. Patients who previously received rituximab and bendamustine often responded well, with many experiencing complete remission. Although uncertainty remains about how RBM compares to the standard BEAM treatment for lymphoma, RBM is expected to cause fewer side effects. Overall, these findings offer hope for its effectiveness in managing these conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Parastoo Dahi, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for elderly patients aged 65-69 with certain health scores or anyone 70 and older, who have multiple myeloma or B-cell lymphoma. They must be in good physical condition, respond to previous treatments, and agree to contraception. Excluded are those with recent heart attacks or strokes, specific treatment failures, CNS involvement history, or prior stem cell transplants.

Inclusion Criteria

Additional eligibility for both the phase I and dose expansion cohort: Patients between the ages of 65 to 69 years old with a Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) score of 3 or higher, Any patient age 70 years old or older, KPS ≥ 70, Males must agree to use an acceptable form of contraception, Complete or partial response to salvage chemotherapy by IWG Working Group Criteria, Cardiac ejection fraction of ≥ 45%, Hemoglobin-adjusted diffusing capacity of carbon monoxide (DLCO) of ≥45%, Creatinine clearance of ≥50 mL/min, Completion of most recent salvage therapy within 8 weeks of enrollment, Direct bilirubin ≤2.0 mg/dL in the absence of suspected Gilbert's disease (if Gilbert's disease is suspected, the total bilirubin must be ≤3.0 mg/dL), and AST ≤ 2.5 ULN

I have been diagnosed with multiple myeloma, relapsed/refractory DLBCL, or transformed indolent lymphoma.

I have multiple myeloma or B-cell non-Hodgkin lymphoma.

Exclusion Criteria

My lymphoma has worsened since my last treatment, or I've had a stem cell transplant, or my previous treatment included bendamustine, or I've had a heart attack or stroke in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive rituximab, bendamustine, and melphalan as conditioning regimen before autologous stem cell transplantation

11 days

Multiple visits for drug administration

Autologous Stem Cell Transplantation

Reinfusion of participants' own stem cells

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Stem Cell Transplantation (ASCT)
• Bendamustine
• Melphalan
• Rituximab

Trial Overview The RBM regimen being tested combines rituximab (an antibody), bendamustine (chemotherapy), and melphalan (another chemotherapy) followed by the patient's own stem cells reinfused back into their body. This study aims to see if RBM has fewer side effects compared to the standard BEAM regimen while treating lymphoma effectively.

How Is the Trial Designed?

Group I: rituximab, bendamustine & melphalan and ASCT Experimental Treatment 4 Interventions

This is a phase I study of rituximab, bendamustine and melphalan (RBM) conditioning followed by ASCT in elderly patients with B-cell NHL. Conditioning regimen consist of rituximab 375 mg/m2 on days -11 and -4, bendamustine 160 mg/m2 intravenously on days -3 and -2; melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0. The conditioning timeline can be modified if there are patient scheduling conflicts. Patients who are deemed inevaluable will be replaced for the primary objective. Patients will be considered inevaluable if they don't receive one dose of conditioning regimen and are removed from the study.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03352765

A Phase I Study of Bendamustine and Melphalan ... Compared to the standard BEAM regimen, this RBM regimen may or may not be less effective in lymphoma, but will likely have fewer side effects. Official Title. A ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3507533/

Autologous Stem Cell Transplantation for Aggressive ... Our group designed an Italian multicenter phase I–II study to evaluate the safety and the efficacy of increasing doses of bendamustine (160 mg/m2, 180 mg/m2 and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723019462

214 Phase I Study of Bendamustine and Melphalan ... Bendamustine/melphalan conditioning for AHCT in the elderly with NHL/MM is safe with limited toxicity, and tolerable per patient reported outcomes.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9631687/

Bendamustine or high-dose cytarabine-based induction ... The overall response rate (ORR) to R-B was 90% (54% complete response [CR]); 77% of patients proceeded to autologous stem cell transplantation (ASCT) and 78% ...

5. astctjournal.org astctjournal.org/article/S1083-8791(17)30575-X/fulltext

Long-Term Results of High-Dose Therapy and Autologous ... These results support a benefit with maintenance rituximab for all MCL patients treated with ASCT. Key Words. Autologous hematopoietic cell transplantation ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... Further analysis showed that this ibrutinib-containing regimen without autologous stem-cell transplantation (ASCT) was superior to the ASCT ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4840280/

Optimal use of bendamustine in hematologic disorders A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2013 ...