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

Trial Summary

What is the purpose of this trial?

Now haplo stem cell transplant using bone marrow or peripheral blood is becoming more feasible with better regimens to prevent graft versus host disease (GVHD) like post transplant cyclophosphamide , tacrolimus, mycophenolate . Recently Bortezomib has also been shown to inhibit dendritic cells maturation and function and possesses a number of other favorable immunomodulatory effect that can prevent GVHD and help enhance immune reconstitution. this study is to assess the engraftment rate in patients with hematologic malignancies who need allogeneic stem cell transplant but do not have a suitable matched related or unrelated stem cell donor and will get T-cell replete HLA-Haploidentical allogeneic peripheral stem cell transplantation using post transplant Cyclophosphamide and bortezomib

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.

What data supports the effectiveness of the drug Bortezomib (Velcade) for blood cancer?

Bortezomib (Velcade) has shown effectiveness in treating multiple myeloma and mantle cell lymphoma, improving progression-free survival in patients unsuitable for stem-cell transplantation. It has also demonstrated positive responses in clinical trials for relapsed and refractory multiple myeloma, indicating its potential benefit in blood cancers. ^{1 2 3 4 5}

Is the combination of stem cell transplant and bortezomib safe for treating blood cancer?

Bortezomib (also known as Velcade) has been studied for safety in treating multiple myeloma and mantle cell lymphoma, often in combination with other drugs. Common side effects include blood-related issues like low platelet counts (thrombocytopenia) and low white blood cell counts (neutropenia), as well as nerve damage (neuropathy). Regular monitoring for these side effects is important. ^{3 4 5 6 7}

How is the drug Bortezomib unique in treating blood cancer?

Bortezomib is unique because it is a proteasome inhibitor that disrupts the breakdown of proteins in cancer cells, enhancing their sensitivity to other treatments and potentially overcoming drug resistance. It is administered intravenously in a specific schedule, which differs from many other treatments for blood cancer. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Position statement on the use of bortezomib in multiple myeloma. [2015]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Bortezomib in multiple myeloma: a practice guideline. [2015]

6. China pubmed.ncbi.nlm.nih.gov

[Outcome of bortezomib plus chemotherapy with or without stem cell transplantation for treatment of multiple myeloma]. [2015]

7. Italy 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. [2022]