Chemotherapy + Stem Cell Transplant for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Disqualifiers: Peripheral neuropathy, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 101

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy drugs and a stem cell transplant to evaluate their effectiveness for individuals with high-risk multiple myeloma, a type of blood cancer. The study aims to determine the optimal dose and assess the side effects of bortezomib (Velcade) when combined with other treatments such as fludarabine (Fludarabine Phosphate), melphalan, and possibly total marrow irradiation. Individuals diagnosed with multiple myeloma, particularly those whose disease has worsened or returned after previous treatments, may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in participants, offering them a chance to be among the first to receive this combination therapy.

Will I have to stop taking my current medications?

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 combination of bortezomib, fludarabine phosphate, and melphalan is generally well-tolerated by patients with multiple myeloma. In earlier studies, some patients experienced side effects, but these were manageable. For instance, one study found that only one in three patients had a side effect that limited their dose. This indicates that while there are some risks, the treatment might be safe for many patients.

When total marrow irradiation (TMI) was added to the treatment, similar results emerged. In a study with eight patients, only one experienced significant side effects. This suggests that adding TMI does not greatly increase the risk of severe side effects. There were no reports of the body rejecting transplanted cells, which is a positive sign for the treatment's safety.

Overall, while more research is needed, the safety data so far is encouraging. Earlier trials have shown that the combination of these treatments has acceptable levels of side effects. Prospective participants in a clinical trial may find these findings reassuring regarding the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they incorporate a unique combination of chemotherapy drugs with a stem cell transplant and total marrow irradiation (TMI). Unlike the standard treatments that typically use just chemotherapy or autologous stem cell transplants alone, this approach uses bortezomib, fludarabine phosphate, and melphalan to potentially enhance the effectiveness of the treatment. TMI is also distinctive as it targets the entire bone marrow, which could lead to better eradication of cancer cells. This combined strategy aims to improve outcomes by delivering a more comprehensive attack on the cancer, offering hope for more effective and longer-lasting remission.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that using bortezomib with fludarabine and melphalan can effectively treat multiple myeloma, a type of blood cancer. In this trial, participants in Group II will receive bortezomib, fludarabine phosphate, and melphalan. One study found that this combination, along with other treatments, helped some patients achieve complete remission, meaning no signs of cancer were detectable. Another study found that adding bortezomib to fludarabine and melphalan improved patient outcomes.

Participants in Group I will receive bortezomib, fludarabine phosphate, melphalan, and total marrow irradiation (TMI). Using TMI with these drugs may enhance the treatment's effectiveness by better preparing the body for a stem cell transplant. Early results are promising, suggesting this treatment might benefit patients with high-risk multiple myeloma. ^{2 4 5 6 7}

Who Is on the Research Team?

Firoozeh Sahebi, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for high-risk stage I or II multiple myeloma patients who have relapsed on new therapies, had a previous stem cell transplant, or have specific genetic changes. They must be able to lie down for about an hour and meet certain health criteria like good heart function and kidney function. People with severe peripheral neuropathy, major medical issues, HIV, active hepatitis B or C, liver cirrhosis, or untreated infections cannot join.

Inclusion Criteria

Your disease has come back or not responded to new targeted treatments like thalidomide, lenalidomide, bortezomib, carfilzomib, or pomalidomide.

Recipient must have signed a voluntary, informed consent in accordance with institutional and federal guidelines

You have multiple myeloma that has come back after a previous treatment with your own stem cells.

Exclusion Criteria

Major medical or psychiatric disorders that would seriously compromise patient tolerance of this regimen

DONOR: Donors will be excluded if for medical or psychological reasons they are unable to tolerate the procedure of peripheral stem cell donation

You have severe peripheral neuropathy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Patients receive fludarabine phosphate and melphalan, with or without total marrow irradiation, as a preparative regimen for allogeneic hematopoietic stem cell transplant

9 days

Daily visits for treatment administration

Transplant

All patients undergo allogeneic peripheral blood stem cell transplant

1 day

1 visit (in-person)

GVHD Prophylaxis

Patients receive tacrolimus and sirolimus to prevent graft-versus-host disease

Starting from day -3, ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Follow-up at day 100, 6 months, and annually thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Fludarabine Phosphate
• Melphalan
• Peripheral Blood Stem Cell Transplantation
• Total Marrow Irradiation

Trial Overview The trial tests the side effects and best dose of bortezomib combined with fludarabine phosphate and melphalan chemotherapy drugs. Some patients will also receive total marrow irradiation before donor stem cell transplant to see if it helps stop cancer growth and prevents immune rejection.

How Is the Trial Designed?

Group I: Group II (bortezomib, fludarabine phosphate, melphalan Experimental Treatment 7 Interventions

Patients receive fludarabine phosphate IV and melphalan IV as in Stratum I. Patients also receive bortezomib IV on days -6, -3, 1, and 4.

Group II: Group I (bortezomib, fludarabine phosphate, TMI, melphalan) Experimental Treatment 8 Interventions

Patients receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4. Patients also undergo TMI BID on days -9 to -7. If no DLT is observed in the first cohort, bortezomib IV will be added on days -6 and -3 for subsequent cohorts.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38483213/

Phase 1 Study of Bortezomib, Fludarabine, and Melphalan, ... Results: Eight patients were enrolled in the TMI arm (stratum I). One of 3 patients in cohort 1 experienced dose-limiting toxicity (DLT), which led to the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01163357

Bortezomib, Total Marrow Irradiation, Fludarabine ... PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fludarabine phosphate and melphalan with or ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636722014671

A Multicenter Phase II, Double-Blind, Placebo-Controlled ... A single-center study demonstrated promising efficacy of bortezomib administered on day -3 along with the backbone of a fludarabine/melphalan conditioning ...

4. astctjournal.org astctjournal.org/article/S1083-8791(16)00190-7/fulltext

Busulfan, Melphalan, and Bortezomib versus High-Dose ... We compared a novel conditioning combination incorporating busulfan, melphalan, and bortezomib (BUMELVEL) versus standard MEL 200 in newly diagnosed patients ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7786301/

Long Term Follow Up of a Novel High Dose Regimen In preclinical studies, both the combination of busulfan and melphalan6 as well the combination of bortezomib and melphalan7 have been shown to be synergistic.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18463870/

updated results of a phase 1/2 study after longer follow-up Updated data from our phase 1/2 study assessing the safety and efficacy of bortezomib plus melphalan in relapsed/refractory multiple myeloma (MM) are presented.

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/01/NCT01453101/Prot_SAP_000.pdf

Protocol Number: Pro00001261 Multiple Myeloma Using a Conditioning Regimen of Fludarabine, Melphalan, and Bortezomib. Protocol Version: Date of Protocol: Original, v.1.