Alternating Ixazomib Citrate and Lenalidomide as Maintenance Therapy After Stem Cell Transplant in Treating Patients With Multiple Myeloma

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02619682
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 90
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II trial studies the safety of alternating ixazomib citrate and lenalidomide as treatment to help keep cancer from coming back after stem cell transplant (maintenance therapy) in treating patients with multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stimulate the immune system to attack cancer cells. Giving ixazomib citrate and lenalidomide as maintenance therapy after transplant may prolong the length of time until the cancer returns.

Condition or Disease	Intervention/Treatment	Phase
Plasma Cell Myeloma; Transplant-Related Carcinoma	Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate the toxicity of the use of ixazomib (ixazomib citrate) and lenalidomide as maintenance therapy after autologous transplant.

SECONDARY OBJECTIVES:

1. Evaluate the ability to deliver the planned therapy.

2. Assess initial response to therapy.

3. Evaluate the median time to disease progression.

4. Assess overall survival.

OUTLINE:

Within 30-120 days after completion of autologous transplant, patients receive ixazomib citrate orally (PO) on days 1, 8 and 15 every 28 days for 2 courses, followed by lenalidomide PO once daily (QD) on days 1-28 for 2 courses. Treatment repeats, alternating after every 2 courses, for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Alternating the Administration of Ixazomib and Lenalidomide as Maintenance Therapy After Autologous Transplant for Treating Multiple Myeloma
• Actual Study Start Date: Dec 30, 2015
• Actual Primary Completion Date: Jun 1, 2022
• Anticipated Study Completion Date: Jul 1, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (ixazomib citrate and lenalidomide) Within 30-120 days after finishing autologous transplant, patients receive ixazomib citrate PO on days 1, 8 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-28. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients will continue to alternate between ixazomib citrate and lenalidomide every 2 courses for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Ixazomib Citrate; Given PO; Other Names: MLN-9708 MLN9708 Ninlaro ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0 [2 years]

   Adverse events Toxicity during the 24 months of post autologous transplant maintenance therapy

Secondary Outcome Measures

1. Overall Survival [Up to 2 years post-treatment]

   all MM patients who got post autologous transplant study therapy

2. Time to Disease Progression [Up to 2 years post-treatment]

   Response criteria will be determined by International Myeloma Working Group Criteria. In patients with chemo-refractory disease at the time of ASCT, the therapy will be felt to be promising if median time to progression is > 9 months. If chemo-sensitive disease at time of ASCT, the therapy will be felt to be promising if median time to progression is > 41 months based on Cancer and Leukemia Group B (CALGB) 10014 lenalidomide maintenance study post ASCT. Initial response rates and outcome will be descriptively reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

• Any autologous patient who underwent high dose melphalan (>= 140 mg/m^2) therapy/peripheral blood stem cell (PBSC) rescue for any stage of multiple myeloma and did not participate in another clinical transplant trial whose primary endpoint is also evaluating long-term, disease-free survival or survival; consenting for study between 30 days to 120 days after transplant; earliest can start therapy is 30 days post transplant after recovered from acute toxicity of autologous stem cell transplant (ASCT)

• 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

• Female patients who:

• Are postmenopausal for at least 1 year before the screening visit, OR

• Are surgically sterile, OR

• If they are 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:

• Agree to practice effective barrier contraception during the entire study treatment period and 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)

• Absolute neutrophil count (ANC) >= 1,000/mm^3

• Platelet count (transfusion independent) >= 75,000/mm^3

• 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

Exclusion Criteria:

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

• Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible effects of prior ASCT chemotherapy

• Major surgery within 14 days before enrollment

• 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 ixazomib

• History of central nervous system multiple myeloma involvement

• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment

• 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

• Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 gene (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A gene locus (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

• Ongoing or active systemic infection, active hepatitis 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; patient cannot be allergic to boron

• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing

• 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

• Patient has >= grade 2 peripheral neuropathy, or grade 1 with pain on clinical examination during the screening period

• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial

• Patients with history prior to transplant of progression on lenalidomide therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center

Investigators

• Principal Investigator: Leona Holmberg, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 14, 2021

More Information

Publications

None provided.

• Responsible Party: Leona Holmberg, Professor, Clinical Research Division, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT02619682
• Other Study ID Numbers: 9266; NCI-2015-01861; X16064; 9266; RG9215039
• First Posted: Dec 2, 2015
• Last Update Posted: Aug 2, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Lenalidomide; Ixazomib; Glycine

Study Results

Participant Flow

Pre-assignment Detail	all patients enrolled on study were treated on study

Arm/Group Title	Post Auto Transplant Maintenance Therapy
Arm/Group Description	only one arm of study : all patients treated on study with same maintenance therapy
Period Title: Overall Study
STARTED	30
COMPLETED	16
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Post Autologous Transplant Maintenance
Arm/Group Description	one treatment arm all patients enrolled on study
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	22 73.3%
>=65 years	8 26.7%
Sex: Female, Male (Count of Participants)
Female	7 23.3%
Male	23 76.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.3%
Not Hispanic or Latino	29 96.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.3%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 6.7%
White	27 90%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%
number of participants treated (Count of Participants)
Count of Participants [Participants]	30 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0
Description	Adverse events Toxicity during the 24 months of post autologous transplant maintenance therapy
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Post Autologous Transplant Maintenance
Arm/Group Description	one arm = all enrolled MM patients got post autologous transplant maintenance therapy
Measure Participants	30
Count of Participants [Participants]	30 100%

2. Secondary Outcome

Title	Overall Survival
Description	all MM patients who got post autologous transplant study therapy
Time Frame	Up to 2 years post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time to Disease Progression
Description	Response criteria will be determined by International Myeloma Working Group Criteria. In patients with chemo-refractory disease at the time of ASCT, the therapy will be felt to be promising if median time to progression is > 9 months. If chemo-sensitive disease at time of ASCT, the therapy will be felt to be promising if median time to progression is > 41 months based on Cancer and Leukemia Group B (CALGB) 10014 lenalidomide maintenance study post ASCT. Initial response rates and outcome will be descriptively reported.
Time Frame	Up to 2 years post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	2 years of maintenance therapy plus additional month after completion of study therapy
Arm/Group Title	Post Autologous Transplant Maintenance
Arm/Group Description	one arm = all enrolled MM patients got post autologous transplant maintenance therapy
All Cause Mortality
	Post Autologous Transplant Maintenance
	Affected / at Risk (%)	# Events
Total	6/30 (20%)
Serious Adverse Events
	Post Autologous Transplant Maintenance
	Affected / at Risk (%)	# Events
Total	4/30 (13.3%)
Cardiac disorders
palpitations	1/30 (3.3%)	1
Infections and infestations
pneumonia with sepsis	1/30 (3.3%)	1
Pneumonia without sepsis	1/30 (3.3%)	1
RSV Upper respiratory tract infection	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Post Autologous Transplant Maintenance
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
anemia	4/30 (13.3%)
anemia	1/30 (3.3%)
Gastrointestinal disorders
vomiting	1/30 (3.3%)
diarrhea	1/30 (3.3%)
General disorders
fatigue	2/30 (6.7%)
Infections and infestations
upper respiratory tract infection	4/30 (13.3%)
cellulitis	3/30 (10%)
giardia gastrointestinal infection	1/30 (3.3%)
bronchitis	2/30 (6.7%)
thrush oral	1/30 (3.3%)
Zoster	1/30 (3.3%)
urinary tract infection	1/30 (3.3%)
Investigations
hyperglycemia	2/30 (6.7%)
hypoglycemia	1/30 (3.3%)
lymphocyte decreased	11/30 (36.7%)
lymphocyte decreased	10/30 (33.3%)
WBC decreased	10/30 (33.3%)
WBC decreased	6/30 (20%)
Platelet decreased	7/30 (23.3%)
Platelet decreased	2/30 (6.7%)
Platelet decreased	1/30 (3.3%)
ANC decreased	9/30 (30%)
ANC decreased	7/30 (23.3%)
ANC decreased	2/30 (6.7%)
Creatinine increased	2/30 (6.7%)
ALT increased	1/30 (3.3%)
Metabolism and nutrition disorders
phosphorus decreased	5/30 (16.7%)
hypokalemia	1/30 (3.3%)
albumin decreased	1/30 (3.3%)
Psychiatric disorders
insomnia	1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
pneumonia	1/30 (3.3%)
Skin and subcutaneous tissue disorders
rash	1/30 (3.3%)
rash	2/30 (6.7%)
Vascular disorders
Hypertension	1/30 (3.3%)
hypertension	1/30 (3.3%)
superficial vein blood clot	1/30 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.