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

NCT02308280 | Completed Phase 2 DMC

• 1 other identifier: HMR-MM-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma; High-Risk Cancer

Keywords

High-risk myeloma; Non myeloablative allogeneic transplantation; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Progression-free survival is defined as the duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first. A 2- sided confidence interval for this proportion will be computed. Minimal residual disease results from negativity to positivity using flow cytometry will not be used to define progression.

  At 2 years after allogeneic transplantation

Secondary Outcomes (10)

• Incidence of ≥ grade III non hematologic toxicity (including ≥ grade II peripheral neuropathy) and incidence of ≥ grade IV hematologic toxicity

  At each medical visit up to 5 years from allogeneic transplantation

• Cumulative incidence of grade I-IV and grade II-IV acute GVHD

  At day 100 days, 6 months and 1 year after allogeneic transplantation

• Cumulative incidences of chronic GVHD

  At 1 and 2 years after allogeneic transplantation

• Maximum grades of acute and chronic GVHD

  At each medical visit up to 5 years from allogeneic transplantation

• Response rates and quality of responses

  Before allogeneic transplantation, before bortezomib, 1 year after bortezomib, then every 8 to 12 weeks up to 5 years from allogeneic transplantation

Study Arms (1)

Bortezomib post-transplantation

EXPERIMENTAL

Non myeloablative allogeneic transplantation followed by Bortezomib for 1 year after a Bortezomib-based induction and autologous stem cell transplantation. Bortezomib: 1,3 mg/m2 subcutaneously every 2 weeks for 26 injections.

Drug: Bortezomib following nonmyeloablative allogeneic transplant

Interventions

Bortezomib following nonmyeloablative allogeneic transplant DRUG

Bortezomib 1,3 mg/m2 subcutaneously every 2 weeks for 1 year (26 injections) starting on day +120 from a non myeloablative sibling or 10/10 unrelated allogeneic transplantation

Also known as: Velcade

Bortezomib post-transplantation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Serum intact immunoglobulin ≥ 10 g/L;
• Bence-Jones proteinuria ≥ 200 mg/day;
• 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:
• International Staging System (ISS) III;
• 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.
• 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;
• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead

Study Sites (1)

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Richard LeBlanc, M.D.

  Hôpital Maisonneuve-Rosemont, affiliated to University of Montreal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair holder, Myeloma Canada Chair

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 4, 2014
• Study Start: November 1, 2014
• Primary Completion: September 27, 2018
• Study Completion: September 27, 2023
• Last Updated: October 19, 2023

Record last verified: 2023-10

Locations

CA (1)