- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02168101
Determining the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma
Open-Label Study to Determine the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma, Followed by an Expansion Phase at the Maximum-Tolerated Dose (MTD) - A Phase II Study
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Colorado
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Denver, Colorado, United States, 80218
- Colorado Blood Cancer Institute
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Ohio
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Cincinnati, Ohio, United States, 45242
- Oncology Hematology Care
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Tennessee
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Nashville, Tennessee, United States, 37203
- Tennessee Oncology PLLC
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Texas
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San Antonio, Texas, United States, 78229
- Texas Transplant Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
KEY POINTS:
Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria in patients who received allogeneic transplant due to high-risk prognostic features, such as, but not limited to:
- Chromosome 17p, partial deletion [del(17p)], t(4;14), t(14;16), t(14;20)
- Plasma cell leukemia
- PFS of less than 2 years after autologous stem cell transplant
- Evidence of engraftment of neutrophils (absolute neutrophil count [ANC] >1000 cells/mm3) and platelets (platelets >60,000 cells/mm3) [dose escalation phase] and >50,000 cells/mm3 [dose expansion phase]).
- Achievement of at least a PR prior to allogeneic stem cell transplant
- Adequate liver and kidney function
- Ability to swallow oral medication
- Absence of gastrointestinal symptoms that precludes oral intake and absorption of MLN9708
- Off antibiotics and amphotericin B formulations, voriconazole or other anti-fungal therapy for the treatment of proven, probable or possible infections
- ECOG of ≤ 2
- Life expectancy ≥3 months
- Ability to understand the nature of this study and give written informed consent
Exclusion Criteria:
- Patients with progressive disease when compared to pre-transplant staging as defined by IMWG Uniform Response criteria for Multiple Myeloma.
- Umbilical cord blood transplant
- Patients with > Grade 2 peripheral neuropathy with pain, or ≥ Grade 3 peripheral neuropathy per NCI CTCAE Version 4.0
- Patients with uncontrolled bacterial, viral, or fungal infections
- 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.
- Patients who are pregnant or breastfeeding
- Most recent chemotherapy ≤21 days and ≤ Grade 1 chemotherapy-related side effects, with the exception of alopecia
- Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of MLN9708. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of MLN9708 is required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤14 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy
- Major surgical procedures ≤14 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
- Ongoing or active systemic infection. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C
- Central Nervous System involvement
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Systemic treatment with moderate and strong inhibitors of cytochrome P450 (CYP) 1A2, CYP3A, or clinically significant CYP3A inducers, or use of Ginkgo biloba or St. John's wort within 14 days before study drug administration in the study.
- Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- Graft versus host disease > Grade 2; or GVHD grade 1 or Grade 2 which requires > 0.5 mg/kg methylprednisolone, or equivalent.
There are additional Inclusion/Exclusion criteria. The Study Center will determine if you meet all criteria and will answer any questions you may have about the trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: MLN9708 - 2.3 mg
Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 2.3 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles.
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Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive MLN9708 orally (PO) as monotherapy on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Up to 18 patients will be enrolled in a dose-escalation phase to determine the maximum tolerated dose (MTD). Dose-Escalation Phase: MLN9708 will be administered orally (PO) as monotherapy. Dosing will start at 2.3 mg. If acceptable tolerability is demonstrated, escalations will be made to 3 mg and to a maximum-planned dose (MPD) of 4 mg.
Other Names:
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Experimental: MLN9708 - 3 mg
Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 3 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles.
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Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive MLN9708 orally (PO) as monotherapy on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Up to 18 patients will be enrolled in a dose-escalation phase to determine the maximum tolerated dose (MTD). Dose-Escalation Phase: MLN9708 will be administered orally (PO) as monotherapy. Dosing will start at 2.3 mg. If acceptable tolerability is demonstrated, escalations will be made to 3 mg and to a maximum-planned dose (MPD) of 4 mg.
Other Names:
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Experimental: MLN9708 - 4 mg
Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 4 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles.
|
Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive MLN9708 orally (PO) as monotherapy on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Up to 18 patients will be enrolled in a dose-escalation phase to determine the maximum tolerated dose (MTD). Dose-Escalation Phase: MLN9708 will be administered orally (PO) as monotherapy. Dosing will start at 2.3 mg. If acceptable tolerability is demonstrated, escalations will be made to 3 mg and to a maximum-planned dose (MPD) of 4 mg.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Phase I Patients Receiving 2.3mg, 3mg, or 4mg MLN9708 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Maximum Tolerated Dose
Time Frame: Collected from day of first dose to the end of the first treatment cycle, up to 28 days
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The maximum tolerated dose (MTD) of MLN9708 will be determined as the dose at which ≤1 of 6 patients experiences a DLT during one cycle (28 days) of therapy utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0
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Collected from day of first dose to the end of the first treatment cycle, up to 28 days
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Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety of MLN9708 When Used as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma Multiple Myeloma
Time Frame: Defined as the time from Day 1 of study drug administration until 30 days after treatment completion for up to 2 years.
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Defined as the number of participants with treatment-emergent grade 3/4/5 adverse events/serious adverse events utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0 determined to be related to MLN9708.
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Defined as the time from Day 1 of study drug administration until 30 days after treatment completion for up to 2 years.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Progression-Free Survival (PFS) at 2 Years Post-maintenance Therapy
Time Frame: every 8 weeks for approximately 24 weeks then every 3 months thereafter for 2 years
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PFS is measured from the date of first protocol treatment until date of disease progression or death occurs, or date of last adequate tumor assessment using the International Myeloma Working Group Uniform Response Criteria.
IMWG disease progression is defined as an increase of ≥ 25% from the nadir in at least one of the following criteria: 1) serum M-protein, 2) urine M-protein, 3) only in patients with non-measurable serum and urine M-protein levels: difference in involved and uninvolved FLC levels, 4) Bone marrow plasma cell percentage (absolute % must be ≥10%).
OR Disease progression also could include development of new lytic bone lesions or increase from baseline in size of lytic bone lesion(s); development of new soft tissue plasmacytoma(s) or definite increase from nadir in existing soft tissue plasmacytomas; or development of hypercalcemia
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every 8 weeks for approximately 24 weeks then every 3 months thereafter for 2 years
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Median Overall Survival (OS) at 2 Years Post-allogeneic Stem Cell Transplant (ASCT)
Time Frame: every 8 weeks for approximately 24 weeks after ASCT, then every 3 months thereafter for 2 years.
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Overall survival is measured as the interval from first study treatment until date of death, or date last known alive.
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every 8 weeks for approximately 24 weeks after ASCT, then every 3 months thereafter for 2 years.
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Number of Participants With Incidence of Chronic Graft-versus-host Disease (cGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
Time Frame: from date of enrollment every 28 days, up to 2 years
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Incidence of chronic Graft-versus-host disease GVHD was assessed based on the National Institutes of Health Consensus Development Project on Criteria for Clinical trials in Acute and Chronic Graft-versus-host-disease (Filipovich et al. 2005) from date of randomization until date of first documented progression, or date of death from any cause.
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from date of enrollment every 28 days, up to 2 years
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Number of Participants With Incidence of Acute Graft-versus-host Disease (aGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
Time Frame: from date of enrollment every 28 days, up to 2 years
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Incidence of acute Graft-versus-host disease GVHD was assessed based on the National Institutes of Health Consensus Development Project on Criteria for Clinical trials in Acute and Chronic Graft-versus-host-disease (Przepiorka et al. 1995) from date of randomization until date of first documented progression, or date of death from any cause.
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from date of enrollment every 28 days, up to 2 years
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Carlos Bachier, MD, Texas Transplant Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protease Inhibitors
- Ixazomib
Other Study ID Numbers
- SCRI MM 42
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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