Bortezomib, Melphalan, and Total-Body Irradiation Before Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT01936090 | Completed Phase 1 DMC

• 4 other identifiers: MC1286NCI-2013-01646Mod12-008546-08P30CA015083
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (3)

• MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (phase I)

  Day 36

• The number and severity of all adverse events (phase I)

  Will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.

  Up to 3 years

• Proportion of complete responses (CR) defined as a CR noted as the objective status on two consecutive evaluations (phase II)

  Will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. 95% confidence intervals for the true success proportion will be calculated.

  Up to 3 years

Secondary Outcomes (4)

• 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

  At day 100

• Time to progression

  Time from registration to the earliest date with documentation of disease progression, assessed at 1 year

• Time to progression

  Time from registration to the earliest date with documentation of disease progression, assessed at 2 years

• Maximum grade for each type of adverse event

  Up to 3 years

Other Outcomes (2)

• Proportion of patients who achieve MRD negative status estimated by the number of patients who are MRD negative divided by the total number of evaluable patients who achieve a CR

  Up to 3 years

• Abnormal ratio and suppressed uninvolved immunoglobulin assessed by HevyLite assay

  Up to 3 years

Study Arms (1)

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

EXPERIMENTAL

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.

Drug: Bortezomib; Radiation: Total-Body Irradiation; Drug: Melphalan; Procedure: Autologous Bone Marrow Transplantation; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Laboratory Biomarker Analysis

Interventions

Bortezomib DRUG

Given IV

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TBI, Total Body Irradiation, Whole-Body Irradiation

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

Melphalan DRUG

Given IV

Also known as: Alkeran

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

Autologous Bone Marrow Transplantation PROCEDURE

Undergo autologous bone marrow transplant

Also known as: ABMT, Autologous Bone Marrow Transplant, Autologous Marrow Transplantation

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Also known as: Autologous Stem Cell Transplantation

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous peripheral blood stem cell transplant

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (bortezomib, TBI, melphalan, stem cell transplant)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Whole-Body Irradiation; Melphalan; Peripheral Blood Stem Cell Transplantation

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; Radiotherapy; Therapeutics; Investigative Techniques; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Study Officials

• Shaji Kumar

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2013
• First Posted: September 5, 2013
• Study Start: August 1, 2013
• Primary Completion: February 2, 2016
• Study Completion: February 16, 2018
• Last Updated: May 24, 2018

Record last verified: 2018-05

Locations

US (1)