Nonmyeloablative Allogeneic Stem Cell Transplant Followed by Bortezomib in High-risk Multiple Myeloma Patients

• Status: Active, not recruiting
• Trial end date: 2023-09-27
• Target enrollment: 0
• Participant gender: All

Summary

Multiple myeloma is a morbid disease associated with a poor outcome, particularly those with high-risk cytogenetics. While standard therapies have modestly improved survival in these high-risk patients, myeloma remains incurable. To date, the only potential curative treatment remains allogeneic hematopoietic stem cell transplantation. However, the high incidences of toxicities including chronic GVHD and disease progression are currently the two most important obstacles to this therapy. Better approaches to maintain and improve benefits of allogeneic transplant, while decreasing toxicity, are urgently needed.

The investigators hypothesize that Bortezomib administration after non myeloablative allogeneic hematopoietic stem cell transplantation in high-risk myeloma patients might improved the outcome of these patients by decreasing myeloma relapse and the severity of chronic GVHD while preserving the graft-versus-myeloma effect. Our goal is to improve the poor clinical outcome of high-risk myeloma patients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Maisonneuve-Rosemont Hospital
• Treatments: Bortezomib; Polystyrene sulfonic acid

Criteria

Inclusion Criteria:

• Age 18 to 65 years, inclusively

• Newly diagnosed multiple myeloma patients (according to IMWG criteria) with measurable disease at diagnosis, based on presence of any of the following:

1. Serum intact immunoglobulin ≥ 10 g/L;

2. Bence-Jones proteinuria ≥ 200 mg/day;

3. Serum free light chain (sFLC) assay ≥ 100 mg/L (difference between involved and uninvolved FLC levels) and an abnormal sFLC ratio

• High-risk patients presenting any of the following:

1. International Staging System (ISS) III;

2. del(17p13), t(4;14) with ISS II or III, t(14;16), t(14;20) and chromosome 1 abnormalities by FISH. At this time, there is no international consensus on the threshold to consider these cytogenetic abnormalities as significant. For this study, investigators will consider arbitrarily a percentage ≥ 10% as significant.

3. Plasma cell leukemia,defined as an absolute blood plasma cell count > 2 x 109/L and the presence of > 20% plasma cells among peripheral blood white cells;

4. Patients ≤ 50 years, regardless of cytogenetics or ISS stage

• Having received a Bortezomib-containing regimen (VTD, CyBorD, VRD or PAD [in patients with PCL]) for a minimum of 4 cycles with ≥ PR.

• Received high-dose Melphalan ≥ 140 mg/m2 followed by autologous stem cell transplantation.

• Available HLA-identical sibling donor or 8/8 allele matched (HLA-A, -B, -C, -DR) matched unrelated donor

Exclusion Criteria:

• Failure to achieve at least PR with a Bortezomib-based induction therapy.

• Progressive disease at any time

• Having received tandem autologous stem cell transplantation.

• Having received maintenance or consolidation therapy with Bortezomib after ASCT. If delays to allogeneic transplant are expected, Lenalidomide at 10 mg die for a maximum of three months will be allowed after ASCT (initiated after day +90) and discontinued at least 14 days before the start of the conditioning regimen.

• Karnofsky score < 70% or comorbidity index HCT-CI > 3.

• Bilirubin > 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis; AST and ALT > 2.5 x ULN; alkaline phosphatase > 5 x ULN.

• Peripheral neuropathy or neuropathic pain ≥ grade II.

• Poor organ function

• Known hypersensitivity to boron, mannitol or Bortezomib.

• Active infection with any of the following viruses: HIV, HTLV-1 or 2, hepatitis B (defined as HBsAg positivity) or hepatitis C (defined as anti-HCV positivity or HCV-RNA positivity).

• Presence of another malignancy with an expected survival estimated < 75% at 5 years (complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, complete resection of a ductal carcinoma in situ of the breast, presence of lobular carcinoma in situ of the breast, complete resection of carcinoma in situ of the cervix, or an in situ or low-risk prostate cancer after curative therapy are not exclusion criteria).

• Positive β-hCG pregnancy test. Female study participants who are surgically sterile (hysterectomy) or who have been postmenopausal for at least 12 consecutive months are automatically eligible for this criterion.

• Study participants not agreeing to remain abstinent or to practice double-barrier forms of birth control from trial screening through 90 days from the last dose of Bortezomib.

• Women who are lactating.

• Women of childbearing potential who are planning to become pregnant while enrolled in this study up to 30 days after the last Bortezomib injection.

• Participation in a trial with an investigational agent within 30 days prior to entry in the study.

• Inability to provide written informed consent prior to initiation of any study-related procedures, and inability, in the opinion of investigators, to comply with all requirements of the study

• Estimated probability to survive less than 6 months after allogeneic transplant.

• Suspicion of cardiac amyloidosis.

• Current history of drug and/or alcohol abuse.