Ixazomib Citrate and Lenalidomide After Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01718743

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

131.9

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies how well ixazomib citrate and lenalidomide after stem cell transplant work in treating patients with newly diagnosed multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving ixazomib citrate together with lenalidomide may be effective in treating multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Hematopoietic Cell Transplantation Recipient Plasma Cell Myeloma	Drug: Ixazomib Citrate Drug: Lenalidomide Other: Questionnaire Administration	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

Establish safety and efficacy of oral ixazomib citrate (MLN 9708) and lenalidomide in the maintenance setting post autologous stem cell transplant (ASCT) in myeloma patients.

SECONDARY OBJECTIVES:

Incidence of secondary primary malignancy. II. Evaluate the best response rate (stringent complete response [sCR]/near complete response [nCR]/very good partial response [VGPR]/partial response [PR]).
Evaluate time to progression. IV. Evaluate time to next therapy. V. Evaluate the tolerability and toxicity. VI. Evaluate M. D. Anderson Symptom Inventory (MDASI)-myeloma symptom evaluation.

OUTLINE:

Beginning 60-180 days post-transplant, patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

88 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of the Combination of MLN 9708 With Lenalidomide as Maintenance Therapy Post Autologous Stem Cell Transplant in Patients With Multiple Myeloma

Actual Study Start Date :

Dec 3, 2012

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ixazomib citrate, lenalidomide) Beginning 60-180 days post-transplant, patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Ixazomib Citrate Given PO Other Names: MLN-9708 MLN9708 Ninlaro Drug: Lenalidomide Given PO Other Names: CC-5013 CC5013 CDC 501 Revlimid Other: Questionnaire Administration Ancillary studies

Arm

Intervention/Treatment

Experimental: Treatment (ixazomib citrate, lenalidomide)

Beginning 60-180 days post-transplant, patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Ixazomib Citrate

Given PO

Other Names:

MLN-9708

MLN9708

Ninlaro

Drug: Lenalidomide

Given PO

Other Names:

CC-5013

CC5013

CDC 501

Revlimid

Other: Questionnaire Administration

Ancillary studies

Outcome Measures

Primary Outcome Measures

Progression-free survival [Time from autologous stem cell transplant (ASCT) to time of clinical progression or death or the time of last contact, assessed up to 30 days after completion of study treatment]
Monitored using the method of Thall et al. Estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
Incidence of adverse events [28 days]
Toxicity data will be summarized by frequency tables.

Secondary Outcome Measures

Best response rate (stringent complete response [sCR]/near complete response [nCR]/very good partial response [VGPR]/partial response [PR]) [Up to 30 days after completion of study treatment]
Estimated along with 95% confidence intervals.
Treatment-related unmanageable toxicities, including grade 3 non-hematologic effects, or grade 4 hematologic effects [Up to 30 days after completion of study treatment]
Toxicity data will be summarized by frequency tables.
Incidence of new primary malignancy [Up to 30 days after completion of study treatment]
Estimated along with 95% confidence intervals.
Overall survival [Up to 30 days after completion of study treatment]
Estimated using the Kaplan-Meier method. Cox proportional hazards model will be used to include multiple covariates. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
M. D. Anderson Symptom Inventory (MDASI)-myeloma symptom evaluation [Up to 30 days after completion of study treatment]
Analyzed with descriptive analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must have undergone autologous stem cell transplantation, with melphalan as a preparative regimen, within 12 months of initiation of induction therapy for newly diagnosed myeloma
Time to initiation of maintenance therapy; patients may start maintenance therapy as early as 60 days post-transplant and up to 180 days post-transplant; as long as they meet the following criteria:
Platelet count >= 100,000/mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
Neutrophil count >= 1000/mm^3; (no growth factors within 5 days prior to first dose of the study drug)
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
Creatinine < 2.5 mg/dL
Recovered (i.e., =< grade 1 toxicity) from the reversible effects of autologous stem cell transplant
Patients whose primary therapy was changed due to suboptimal response of toxicity will be eligible, however no more than 2 regimens will be allowed prior to ASCT
Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 to 2
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
Female patients who: are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent, during study treatment and for 90 days after the last dose of study treatment, AND
Must also adhere to guidelines of any treatment-specific pregnancy prevention program, if applicable, 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: agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study treatment, OR
Must also adhere to guidelines of any treatment-specific pregnancy prevention program, if applicable, 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)

Exclusion Criteria:

Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
Major surgery within 14 days before the first dose of study drug
Radiotherapy within 14 days before enrollment; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708
Known active central nervous system involvement
Systemic treatment, within 14 days before study enrollment, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), 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
Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment
Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
Female subject who are lactating or have a positive serum pregnancy test during the screening period
Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation or completion of treatment according to this protocol
Corrected QT interval using Bazett's formula (QTcB) > 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period; if a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
Ongoing or active systemic infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus hepatitis
Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
Known allergy to any of the study medications, their analogues, or excipients in the various formulations
Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection