Multiple Myeloma
Conditions
Keywords
Relapsed Multiple Myeloma, Refractory Multiple Myeloma, Bendamustine, Bortezomib, Lenalidomide, Dexamethasone, Treanda, Velcade, Revlimid
Brief summary
The purpose of the study is to determine the safety and efficacy of the use of bendamustine in combination with a commonly used combination chemotherapy to treat relapsed and refractory multiple myeloma. The study will be conducted in two phases. Participants in phase I will receive 1 of 4 escalating doses of bendamustine. Once the maximum tolerated dose of bendamustine is determined, phase II of this trial will begin. Participants in phase II will receive the maximum tolerated dose of bendamustine in combination with standard of care chemotherapy.
Detailed description
Multiple myeloma is a multi-organ neoplastic disorder caused by the clonal proliferation of plasma cells. It has an incidence of about 4.5/100,000 per year in the U.S., making it the second most common hematologic malignancy. For many years, alkylating agents have been the backbone of treatment. The combination of melphalan and prednisone was, for many years, the standard of care for patients who were not candidates for autologous transplantation. Melphalan continues to be the primary conditioning agent for autologous transplant,and cyclophosphamide has also gained a foothold in the treatment of this disease. The introduction of novel agents has fundamentally changed the landscape of treating this disease, although the true effects on survival are not yet known. Immunomodulatory agents and proteosome inhibitors, including thalidomide, lenalidomide and bortezomib have been used in both newly diagnosed and relapsed patients. Currently, there is intense clinical research on the optimal way to combine these novel agents with the traditional backbones of treatment - including alkylators, with one another and, eventually, with the subsequent iterations of these classes of drugs. However, despite the therapeutic excitement surrounding this disease, most patients will relapse and a cure remains an elusive goal.
Interventions
DRUGBendamustine
The first group of three patients to enter the study will receive a 25 mg/m\^2 dose of bendamustine. If this dose is found to be safe, the next three patients will receive 50 mg/m\^2. Using a modified Fibonacci dose-escalation design, the dose will continue to increase at a rate of 25 mg/m\^2 until the highest safe dose of bendamustine is found. The maximum dose will be 125 mg/m\^2. Bendamustine and bortezomib will be given through a catheter twice a week every 21 days. Dexamethasone and lenalidomide will be given orally. In general, a cycle of chemotherapy will last 21 days.
Sponsors
Celgene
Loyola University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults with relapsed and/or refractory myeloma who have received between 1-4 prior lines of therapy * Must have adequate liver and renal function * Zubrod Performance Status (ZPS) of 2 or better * Must have measurable disease
Exclusion criteria
* Peripheral neuropathy of grade II or higher * Thrombocytopenia (platelets less than 50,000/uL) * Neutropenia (ANC\<1000/uL) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.4 X ULN * Total bilirubin \>1.5 X upper limit of normal (ULN) * Creatinine clearance of less than 45 milliliters per minute (mL/min) * Patients with HIV * Patients with active hepatitis * Pregnant or lactating women * Individuals of child-bearing potential not using adequate contraception * Individuals unable to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing a Toxicity | 21 days | The number of patients experiencing at least one toxicity at the lowest dose of bendamustine. A toxicity is defined as one or more of the following: Upper respiratory infection; anemia; thrombocytopenia; neutropenia; shortness of breath on exertion; decreased appetite; nausea; neuropathy; anxiety; arthritis; and hypercalcemia. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from May 2011 through April 2014 (36 months) from the Cardinal Bernardin Cancer Center at Loyola University Medical Center
Pre-assignment details
There are no pre-assignment details to report
Participants by arm
| Arm | Count |
|---|---|
| Bendamustine Bendamustine is combined with standard chemotherapy | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Bendamustine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Patients Experiencing a Toxicity
The number of patients experiencing at least one toxicity at the lowest dose of bendamustine. A toxicity is defined as one or more of the following: Upper respiratory infection; anemia; thrombocytopenia; neutropenia; shortness of breath on exertion; decreased appetite; nausea; neuropathy; anxiety; arthritis; and hypercalcemia.
Time frame: 21 days
Population: No patients were analyzed as study was terminated early after external sponsor withdrew support. Therefore, data necessary for planned analyses were not collected.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bendamustine | Number of Patients Experiencing a Toxicity | Experienced no toxicities | 0 Participants |
| Bendamustine | Number of Patients Experiencing a Toxicity | Experienced at least one toxicity | 3 Participants |