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

• Register: ClinicalTrials.gov
• Last refreshed on: 30 October 2023
• Main ID: NCT02308280
• Date of registration: 01/12/2014
• Prospective Registration: No
• Primary sponsor: Maisonneuve-Rosemont Hospital
• Public title: Nonmyeloablative Allogeneic Stem Cell Transplant Followed by Bortezomib in High-risk Multiple Myeloma Patients
• Scientific title: A Phase II, Open-label Study of Bortezomib Following Nonmyeloablative Allogeneic Stem Cell Transplant in Patients With High-risk Multiple Myeloma
• Date of first enrolment: November 2014
• Target sample size: 40
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02308280
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada

Contacts

• Name: Richard LeBlanc, M.D.
• Affiliation: Hôpital Maisonneuve-Rosemont, affiliated to University of Montreal

Key inclusion & exclusion 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 ß-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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

High-Risk Cancer

Multiple Myeloma

Intervention(s)

Drug: Bortezomib following nonmyeloablative allogeneic transplant

Primary Outcome(s)

Progression-free survival [Time Frame: At 2 years after allogeneic transplantation]

Secondary Outcome(s)

Response rates and quality of responses [Time Frame: Before allogeneic transplantation, before bortezomib, 1 year after bortezomib, then every 8 to 12 weeks up to 5 years from allogeneic transplantation]

Overall survival [Time Frame: At 2 years]

Incidence of = grade III non hematologic toxicity (including = grade II peripheral neuropathy) and incidence of = grade IV hematologic toxicity [Time Frame: At each medical visit up to 5 years from allogeneic transplantation]

Incidence of relapse [Time Frame: At 2 years]

Nonrelapse mortality [Time Frame: At 100 days and 2 years]

Quality of life after allogeneic transplantation [Time Frame: Evaluated before allogeneic transplantation, at 100 days from transplantation, before Bortezomib administration, then every 3 months up to 5 years from allogeneic transplantation]

Cumulative incidences of chronic GVHD [Time Frame: At 1 and 2 years after allogeneic transplantation]

Minimal residual disease on bone marrow using multiparametric flow cytometry [Time Frame: Before the allogeneic transplantation, before Bortezomib administration (day +120), at 3, 6, 9, 12, 15, 18, 21 and 24 months from day +120 of the allogeneic transplantation]

Cumulative incidence of grade I-IV and grade II-IV acute GVHD [Time Frame: At day 100 days, 6 months and 1 year after allogeneic transplantation]

Maximum grades of acute and chronic GVHD [Time Frame: At each medical visit up to 5 years from allogeneic transplantation]

Secondary ID(s)

HMR-MM-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors