This trial is active, not recruiting.

Conditions ds stage i plasma cell myeloma, ds stage ii plasma cell myeloma, ds stage iii plasma cell myeloma, refractory plasma cell myeloma
Treatments bortezomib, total-body irradiation, melphalan, autologous bone marrow transplantation, autologous hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, laboratory biomarker analysis
Phase phase 1/phase 2
Target proteasome
Sponsor Mayo Clinic
Collaborator National Cancer Institute (NCI)
Start date August 2013
End date October 2017
Trial size 11 participants
Trial identifier NCT01936090, MC1286, Mod12-008546-08, NCI-2013-01646, P30CA015083


This phase I/II trial studies the side effects and best dose of bortezomib when given together with melphalan, and total-body irradiation before stem cell transplant and to see how well it works in treating patients with multiple myeloma. Giving chemotherapy and total-body irradiation before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. The stem cells that were collected from the patient's blood or bone marrow are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and total-body irradiation.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
Conditioning regimen: Patients receive bortezomib IV on days -5 and -2, TBI BID on days -5 and -2, and melphalan IV over 1 hour on days -4 and -3. Transplant: Patients undergo autologous bone marrow or peripheral blood stem cell transplant on day 0.
Given IV
total-body irradiation TBI
Undergo TBI
melphalan Alkeran
Given IV
autologous bone marrow transplantation ABMT
Undergo autologous bone marrow transplant
autologous hematopoietic stem cell transplantation Autologous Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
peripheral blood stem cell transplantation PBPC transplantation
Undergo autologous peripheral blood stem cell transplant
laboratory biomarker analysis
Correlative studies

Primary Outcomes

MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (phase I)
time frame: Day 36
The number and severity of all adverse events (phase I)
time frame: Up to 3 years
Proportion of complete responses (CR) defined as a CR noted as the objective status on two consecutive evaluations (phase II)
time frame: Up to 3 years

Secondary Outcomes

CR rate at day 100 estimated by the total number of patients who achieve a complete CR by day 100 post-transplant divided by the total number of evaluable patients
time frame: At day 100
Time to progression
time frame: Time from registration to the earliest date with documentation of disease progression, assessed at 1 year
Time to progression
time frame: Time from registration to the earliest date with documentation of disease progression, assessed at 2 years
Maximum grade for each type of adverse event
time frame: Up to 3 years

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Serum creatinine =< 2 mg/dL - Serum total bilirubin =< 1.5 X upper limit of normal (ULN) - Platelet count >= 30,000/μL - Hemoglobin >= 8.0 g/dL - Diagnosis of myeloma for which autologous stem cell transplant is being considered - Measurable disease of multiple myeloma at the time of baseline values for disease assessment as defined by at least one of the following: - Serum monoclonal protein >= 1.0 g/dL - >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis - Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio - Bone marrow plasma cells >= 30% - NOTE: - For patients with no relapse prior to transplant, measurable disease at the time of diagnosis - For patients who have had a disease relapse prior to transplant, measurable disease at the time of the most recent relapse immediately prior to transplant. - If the patient had treatment for the relapsed disease prior to transplant, the patient must have measurable disease at the time of relapse prior to this therapy - Patient is considered for autologous stem cell transplantation with full dose melphalan (200 mg/m^2) - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 - Recovered from non-hematological toxicity of previous chemotherapy (excludes grade 1 neurotoxicity) - Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care - Ejection fraction >= 45% - Corrected pulmonary diffusion capacity of greater than or equal to 50% - Forced expiratory volume in one second (FEV1) >= 50% - Forced vital capacity (FVC) >= 50% - Negative pregnancy test performed =< 14 days prior to registration, for women of childbearing potential only - Willing to return to Mayo Clinic Rochester, for treatment and follow-up - Note: During the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up - Willing to provide blood and bone marrow samples for correlative research purposes Exclusion Criteria: - Prior autologous or allogeneic bone marrow/peripheral blood stem cell transplant - More than two prior regimens for therapy of MM - Myocardial infarction within 6 months prior to enrollment, or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; NOTE: prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant - Seroreactivity for human immunodeficiency virus (HIV), human T-cell lymphotrophic virus (HTLV) I or II, hepatitis B virus (HBV), hepatitis C virus (HCV) - Other active malignancy < 2 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy - NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer - Any of the following: - Pregnant women or women of reproductive capability who are unwilling to use effective contraception (2 effective methods of contraception, at the same time) from the time of signing the informed consent through 30 days after the last dose of study treatment, OR unwilling to agree to completely abstain from heterosexual intercourse - Nursing women - Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 30 days after stopping treatment - Unwilling to agree to completely abstain from heterosexual intercourse - Other co-morbidity, which would interfere with patient's ability to participate in the trial, e.g. uncontrolled infection, uncompensated lung disease or psychiatric illness - Concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment - Known allergies to any of the components of the investigational treatment regimen or required ancillary treatments - Patient has >= grade 2 peripheral neuropathy - Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial

Additional Information

Official title Phase I/II Bortezomib, Melphalan and Low Dose TBI Conditioning for Patients Undergoing Autologous Stem Cell Transplantation for Multiple Myeloma
Principal investigator Shaji Kumar
Description PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of bortezomib that can be added to high dose melphalan and low dose total body irradiation as part of conditioning chemotherapy for myeloma. (Phase I) II. To determine the efficacy of the bortezomib added to high dose melphalan and low dose total-body irradiation (TBI) in patients with myeloma undergoing stem cell transplantation, as defined by achievement of complete response (CR). (Phase II) SECONDARY OBJECTIVES: I. To examine the toxicities associated with addition of bortezomib to high dose melphalan and TBI in patients with multiple myeloma (MM). II. To determine the progression free rate at 1 and 2 years. TERTIARY OBJECTIVES: I. To determine the proportion of patients achieving a minimal residual disease (MRD) negative status. II. To assess the HevyLite assay prior to and during treatment. OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II study. CONDITIONING REGIMEN: Patients receive bortezomib intravenously (IV) on days -5 and -2, TBI twice daily (BID) on days -5 and -2, and melphalan IV over 1 hour on days -4 and -3. TRANSPLANT: Patients undergo autologous bone marrow or peripheral blood stem cell transplant on day 0. After completion of study treatment, patients are followed up at 100 days and then every 90 days for up to 3 years.
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Mayo Clinic.