Determining the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma

NCT02168101 | Completed Phase 2 Results

• 1 other identifier: SCRI MM 42
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of the study is to determine the safety of MLN9708 as maintenance therapy following allogeneic stem cell transplant in patients with multiple myeloma.

Conditions

Multiple Myeloma

Keywords

MLN9708; allogeneic stem cell transplant; multiple myeloma; ixazomib; autologous stem cell transplant

Outcome Measures

Primary Outcomes (2)

• Number of Phase I Patients Receiving 2.3mg, 3mg, or 4mg MLN9708 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Maximum Tolerated Dose

  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

  Collected from day of first dose to the end of the first treatment cycle, up to 28 days

• 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

  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.

  Defined as the time from Day 1 of study drug administration until 30 days after treatment completion for up to 2 years.

Secondary Outcomes (4)

• Median Progression-Free Survival (PFS) at 2 Years Post-maintenance Therapy

  every 8 weeks for approximately 24 weeks then every 3 months thereafter for 2 years

• Median Overall Survival (OS) at 2 Years Post-allogeneic Stem Cell Transplant (ASCT)

  every 8 weeks for approximately 24 weeks after ASCT, then every 3 months thereafter for 2 years.

• Number of Participants With Incidence of Chronic Graft-versus-host Disease (cGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708

  from date of enrollment every 28 days, up to 2 years

• Number of Participants With Incidence of Acute Graft-versus-host Disease (aGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708

  from date of enrollment every 28 days, up to 2 years

Study Arms (3)

MLN9708 - 2.3 mg

EXPERIMENTAL

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.

Drug: MLN9708

MLN9708 - 3 mg

EXPERIMENTAL

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.

Drug: MLN9708

MLN9708 - 4 mg

EXPERIMENTAL

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.

Drug: MLN9708

Interventions

MLN9708 DRUG

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.

Also known as: ixazomib

MLN9708 - 2.3 mg; MLN9708 - 3 mg; MLN9708 - 4 mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (4)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Sarah Cannon
• Organization: Sarah Cannon Development Innovations, LLC

CANNDLClinicalScience@HCAHealthcare.com

844-710-6157

Study Officials

• Carlos Bachier, MD

  Texas Transplant Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: June 20, 2014
• Study Start: September 1, 2014
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: February 27, 2020
• Results First Posted: February 27, 2020

Record last verified: 2020-02

Locations

US (4)