Stem Cell Transplant + Bortezomib for Blood Cancer

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Henry Ford Health System

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

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Henry Ford hospital Detroit, MI

Who Is Running the Clinical Trial?

Henry Ford Health System Lead Sponsor

References

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

Clinical update: proteasome inhibitors in hematologic malignancies. [2019] The proteasome inhibitor bortezomib (VELCADE; formerly PS-341, LDP-341, MLN341) is a novel dipeptide boronic acid. In cell culture and xenograft models, bortezomib showed potent activity, enhanced the sensitivity of cancer cells to traditional chemotherapeutics, and appeared to overcome drug resistance. In vitro, bortzomib downregulated the NF-kappaB pathway. NF-kappaB is a transcription factor that enhances the production of growth factors (e.g., IL-6), cell-adhesion molecules, and anti-apoptotic factors, all of which contribute to the growth of the tumor cell and/or protection from apoptosis. Phase II trials have been conducted in patients with relapsed and refractory multiple myeloma (SUMMIT trial, 202 patients) or relapsed myeloma (CREST trial, n=54) using a 1.3mg/m(2) dose given twice weekly for 2 weeks (days 1, 4, 8, 11; rest days 12-21). Both trials showed responses (including complete responses) with manageable toxicities, forming the basis for an ongoing phase III trial comparing response to bortezomib versus high-dose dexamethasone.

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

Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. [2020] Bortezomib (VELCADE) is a potent inhibitor of the 26S proteasome with broad antitumor activity. We performed a phase II study of bortezomib to evaluate its clinical effects in patients with metastatic breast cancer.

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

Position statement on the use of bortezomib in multiple myeloma. [2015] Bortezomib (Velcade) is a boron containing molecule which reversibly inhibits the proteasome, an intracellular organelle which is central to the breakdown of ubiquinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate it is effective for the treatment of relapsed refractory myeloma, and a phase III trial comparing bortezomib to dexamethasone in second/third line treatment showed superiority in progression free and overall survival. It is administered intravenously in the outpatient setting on days 1, 4, 8 and 11 of a 21-day cycle and regular monitoring for side effects is essential. It is currently approved for the treatment of multiple myeloma patients who have received at least one prior therapy and who have already undergone or are unsuitable for transplantation. Given the strength of this data the UK Myeloma Forum and British Committee for Standards in Haematology believe that bortezomib should be available for prescription by UK haematologists according to its licensed indication in patients with relapsed myeloma.

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] Bortezomib (Velcade(®)) is a proteasome inhibitor that is approved for the treatment of multiple myeloma and mantle cell lymphoma (MCL). This article reviews the efficacy and tolerability of bortezomib in combination with rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in the treatment of previously untreated MCL unsuitable for stem-cell transplantation, and overviews the pharmacology of bortezomib. In the large, randomized, assessor-blinded, multinational LYM-3002 trial, induction therapy with VR-CAP improved progression-free survival significantly more than R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) after a median follow-up of 40 months in patients with newly diagnosed MCL ineligible or not considered for stem-cell transplantation. Complete response and certain other secondary endpoints were improved significantly more with VR-CAP than R-CHOP. Overall survival data were not mature at the time of assessment. The improved efficacy with VR-CAP was accompanied by an increased incidence of grade 3 or higher adverse events, particularly haematological adverse events.

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

Bortezomib in multiple myeloma: a practice guideline. [2015] Bortezomib (Velcade™, PS-341), a first-in-class proteasome inhibitor, has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma. We created a provincial guideline for the use of bortezomib, in newly diagnosed individuals (both eligible and ineligible for transplant) and in individuals with relapsed or refractory multiple myeloma.

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

[Outcome of bortezomib plus chemotherapy with or without stem cell transplantation for treatment of multiple myeloma]. [2015] To investigate the efficacy and adverse reaction of bortezomib plus chemotherapy with or without stem cell transplantation (SCT) for treatment of multiple myeloma (MM).

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] The combination of bortezomib (velcade), pulsed dexamethasone and weekly cyclophosphamide (CVD) in relapsed/refractory myeloma patients induces high overall (75%) and complete (31%) response rates compared to velcade/dexamethasone (overall 47%, CR 5%) and velcade alone (overall 27%, CR 0%). The toxicity profiles including thrombocytopenia, neutropenia, and neuropathy were comparable between the groups.