Stem Cell Transplant + Bortezomib for Blood Cancer

Overseen By shatha farhan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Henry Ford Health System

Disqualifiers: HIV, Hepatitis B/C, Infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for individuals with blood cancer who need a stem cell transplant but lack a perfectly matched donor. It combines the drug Bortezomib (Velcade) with a type of stem cell transplant that may aid immune system recovery and reduce complications. The trial targets those with blood cancer who lack a fully matched donor but have a partially matched family member. Participants should manage daily activities independently. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 treatment is likely to be safe for humans?

Research has shown that bortezomib effectively treats several blood cancers, such as multiple myeloma and mantle cell lymphoma. However, past studies revealed that many patients experienced serious side effects, with 76.9% having severe reactions that might require medical attention. These side effects are known risks and have appeared in other trials as well.

The FDA has approved bortezomib for some cancer treatments, indicating it has undergone safety testing in humans. Still, side effects can occur. Participants in clinical trials should discuss potential risks and benefits with their healthcare provider before joining. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for blood cancer?

Researchers are excited about using Bortezomib for blood cancers because it offers a unique approach compared to traditional chemotherapy and radiation treatments. Bortezomib works by targeting and inhibiting a specific protein complex called the proteasome, which is crucial for cancer cell survival and growth. This mechanism can lead to the accumulation of proteins within the cancer cells, causing them to die. Additionally, Bortezomib is often administered in lower doses and can be given via injection, which may result in fewer side effects than conventional therapies. This innovative mechanism and delivery method hold promise for more effective and potentially less toxic treatment options for patients with blood cancer.

What evidence suggests that this treatment might be an effective treatment for blood cancer?

Studies have shown that Bortezomib, which participants in this trial may receive, effectively treats several blood cancers, including multiple myeloma. It stops cancer cells from growing, slowing or halting their spread. Bortezomib also aids the immune system, potentially preventing issues like graft versus host disease (GVHD) after a stem cell transplant. Specifically, it affects dendritic cells, which play a significant role in immune responses. This makes Bortezomib a promising option for improving the success of stem cell transplants in patients without a perfect donor match. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with blood cancers who lack a fully matched donor but have a related half-matched (haploidentical) donor. They should be fit for stem cell transplant, have good organ function, and provide consent. Those with uncontrolled infections, suitable donors, HIV/hepatitis B/C, liver cirrhosis, brain involvement by cancer or pregnant women can't join.

Inclusion Criteria

My kidneys are functioning well, with a creatinine clearance rate of 60 ml/min or higher.

Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for hemoglobin

Bilirubin </= 1.5 mg/dl , aspartate aminotransferase (AST) or alanine aminotransferase (ALT) </= 200 IU/ml for adults

Exclusion Criteria

I do not have any active, uncontrolled infections.

I am not pregnant and can bear children.

I have a donor match for my transplant that meets the specific genetic criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants undergo a conditioning regimen with Fludarabine, Melphalan, and Total Body Irradiation

1-2 weeks

Transplantation

Participants receive HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with post-transplant Cyclophosphamide and Bortezomib

1 week

Follow-up

Participants are monitored for engraftment rate and safety post-transplant

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib

Trial Overview The study tests the effectiveness of using both Cyclophosphamide and Bortezomib after a haploidentical peripheral blood stem cell transplant in patients with hematologic malignancies to prevent GVHD and improve immune recovery.

How Is the Trial Designed?

Group I: Bortezomib Experimental Treatment 1 Intervention

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?

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Published Research Related to This Trial

In the LYM-3002 trial involving patients with untreated mantle cell lymphoma (MCL) unsuitable for stem-cell transplantation, the combination of bortezomib with rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) significantly improved progression-free survival compared to the standard R-CHOP regimen after a median follow-up of 40 months.

While VR-CAP showed better efficacy in achieving complete responses and other secondary endpoints, it was associated with a higher incidence of serious adverse events, particularly hematological issues, indicating a trade-off between effectiveness and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib: A Review in Mantle Cell Lymphoma in Previously Untreated Patients Unsuitable for Stem-Cell Transplantation. McCormack, PL.[2016]

Bortezomib, a proteasome inhibitor, has demonstrated strong anti-cancer activity in cell cultures and animal models, enhancing the effectiveness of traditional chemotherapy and overcoming drug resistance.

In Phase II trials involving 254 patients with relapsed multiple myeloma, bortezomib showed promising response rates and manageable side effects, leading to further investigation in a Phase III trial against high-dose dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical update: proteasome inhibitors in hematologic malignancies. Richardson, P.[2019]

Bortezomib combined with chemotherapy showed an overall response rate of 80.8% in treating multiple myeloma, with a 100% response in newly diagnosed patients, indicating its high efficacy.

While bortezomib treatment can lead to manageable side effects, including peripheral neuropathy and sinus bradycardia, some patients experienced severe adverse reactions, leading to treatment discontinuation in a few cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Outcome of bortezomib plus chemotherapy with or without stem cell transplantation for treatment of multiple myeloma]. Wang, YF., Deng, SH., Wu, T., et al.[2015]

Bortezomib (Velcade) is an effective treatment for relapsed refractory myeloma, showing superior progression-free and overall survival compared to dexamethasone in phase III trials.

It is administered intravenously in a specific schedule (days 1, 4, 8, and 11 of a 21-day cycle) and requires regular monitoring for side effects, highlighting the importance of safety in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Position statement on the use of bortezomib in multiple myeloma. Morgan, GJ., Davies, FE., Cavenagh, JD., et al.[2015]

In a phase II study involving 12 patients with metastatic breast cancer, bortezomib (VELCADE) was well tolerated but did not show objective clinical responses, with only one patient achieving stable disease and the rest experiencing disease progression.

Despite its limited efficacy as a single agent, bortezomib demonstrated a significant reduction in plasma interleukin-6 levels and a mean inhibition of specific chymotryptic activity of 53.1%, suggesting potential for future combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Yang, CH., Gonzalez-Angulo, AM., Reuben, JM., et al.[2020]

The combination treatment of bortezomib, pulsed dexamethasone, and weekly cyclophosphamide (CVD) resulted in a high overall response rate of 75% and a complete response rate of 31% in patients with relapsed/refractory myeloma, significantly outperforming other regimens.

The safety profiles of the CVD combination were similar to those of bortezomib/dexamethasone and bortezomib alone, with comparable rates of side effects like thrombocytopenia, neutropenia, and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Davies, FE., Wu, P., Jenner, M., et al.[2022]

Bortezomib is recommended for use in both newly diagnosed and relapsed/refractory multiple myeloma patients, whether they are eligible for autologous stem cell transplantation or not, based on a systematic review of evidence.

The guidelines also emphasize the importance of monitoring and managing potential toxicities associated with bortezomib treatment, such as the risk of herpes zoster reactivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in multiple myeloma: a practice guideline. Kouroukis, CT., Baldassarre, FG., Haynes, AE., et al.[2015]

Citations

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Bortezomib for the Treatment of Hematologic Malignancies Acute lymphoblastic leukemia (ALL) is the most common malignant disorder in patients aged younger than 15 years, accounting for 26% of all cancers and 78 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1936263/

Bortezomib (Velcade™) in the Treatment of Multiple Myeloma Clinical trials are also underway looking at the use of bortezomib in other hematological malignancies including lymphoma, acute leukemia and solid tumors ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S002432052400715X

Bortezomib in cancer therapy: Mechanisms, side effects ... These transcription factors have been implicated in various diseases and malignancies, including breast cancer [54], prostate cancer [55], non- ...

4. myeloma.org myeloma.org/velcade-bortezomib

Velcade (Bortezomib) & Multiple Myeloma Treatment | IMF Tumor Lysis Syndrome (TLS). TLS is a syndrome that causes a chemical imbalance in the blood that could lead to heart and/or kidney problems. TLS can occur with ...

5. nature.com nature.com/articles/s41408-024-01034-6

Once-weekly versus twice-weekly bortezomib in newly ... Multiple myeloma (MM) is a hematologic malignancy of post-germinal plasma cells [1, 2]. Outcomes in MM have drastically improved over the ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118465573

Safety and Efficacy of Bortezomib (VELCADE™) in 104 ... Overall, 76.9% of the pts experienced Grade 3 & 4 adverse events. Safety profile observed is similar to past trial results with bortezomib. Conclusion: In this ...

7. fda.gov fda.gov/files/drugs/published/21602-Bortezomib-Clinpharm-BPCA.pdf

21602 Bortezomib Clinpharm BPCA Bortezomib PK in adult patients with multiple myeloma (MM) following twice-weekly repeat- dose administration has been described previously in ...

8. aetna.com aetna.com/cpb/medical/data/600_699/0675.html

Bortezomib - Medical Clinical Policy Bulletins Experiments have shown that Velcade (bortezomib) is cytotoxic to many types of cancer cells in vitro. In non‐clinical tumor models Velcade (bortezomib) caused a ...