Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma
Conditions
Multiple Myeloma
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Conditions: Keywords
Multiple Myeloma, Autologous Stem Cell Transplantation, Ixazomib, Lenalidomide, Dexamethasone
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Ixazomib Type: Biological
Name: Lenalidomide Type: Drug
Name: Dexamethasone Type: Drug
Overall Status
Recruiting
Summary
The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.
Detailed Description
Based on the further need to improve progression-free survival and overall survival post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate combination regimens of immunomodulatory drugs and proteasome inhibitors as consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral formulation of ixazomib allows for easier administration when compared to bortezomib.

In this study, following consolidation with IRD, patients will be randomized to maintenance therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 70 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria - Pre-ASCT Inclusion Criteria

Each patient must meet all of the following inclusion criteria prior to ASCT to be screened for the study:

- Between the ages of 18 and 70 years of age (inclusive) at time of enrollment

- Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

- Histologically confirmed diagnosis of symptomatic multiple myeloma. (Patients with multiple myeloma with secondary amyloidosis are eligible.)

- Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy

Female patients must:

- Be postmenopausal for at least 1 year before the screening visit, OR

- Be surgically sterile, OR

- If of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR

- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

- Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:

- To practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR

- To practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

Inclusion Criteria to Begin IRD Consolidation - Maintenance Therapy

- Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2

- Adequate organ function as defined below:

- Absolute neutrophil count (ANC) ≥ 1,000/mm3

- Platelet count ≥ 75,000/mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before study enrollment

- Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.

- Calculated creatinine clearance ≥ 30 mL/min Women of childbearing potential must follow pregnancy testing requirements as outlined in the Revlimid REMS® program material. This is defined as either committing to continued abstinence from heterosexual intercourse or beginning TWO acceptable methods of contraception (one highly effective method and one additional effective method (AT THE SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of study participation, and for 28 days following the last dose of lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a woman of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately

- All study participants must be registered into the mandatory Revlimid REMS® program and be willing to comply with its requirements. Per standard Revlimid REMS® program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS® program

Exclusion Criteria - Pre-ASCT

Patients meeting any of the following exclusion criteria prior to ASCT are not to be screened for the study:

- Female patients who are lactating or have a positive serum pregnancy test during the screening period

- Evidence of MM disease progression or relapse at any time prior to enrollment

- Plasma cell leukemia or MM CNS involvement

- Prior stem cell transplant (autologous or allogeneic)

- Prior organ transplant requiring immunosuppressive therapy

- Planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma from time of ASCT (following neutrophil engraftment) through discontinuation from study. Patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)

- Active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positive

- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent

- Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib

- Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma and secondary amyloidosis)

- Cardiac syncope, uncompensated NYHA Class 3 or 4 congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically important autonomic disease

Exclusion Criteria to Begin IRD Consolidation - Maintenance Therapy

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

- Female patients who are lactating or have a positive serum pregnancy test during the screening period

- Evidence of MM disease progression from time of ASCT Day 0

- Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma from time of ASCT (following neutrophil engraftment) through discontinuation from study. Patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis, etc.)

- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

- Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period

- Major surgery within 14 days prior to start of study treatment

- Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to start of study treatment

- Systemic treatment, within 14 days prior to start of study treatment, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole), or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort

- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days prior to start of study treatment and throughout the duration of this trial
Location
Washington University School of Medicine
St. Louis, Missouri, United States
Status: Recruiting
Contact: Ravi Vij, M.D. - 314-454-8323 - rvij@dom.wustl.edu
Start Date
January 2015
Completion Date
April 2021
Sponsors
Washington University School of Medicine
Source
Washington University School of Medicine
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page