Ixazomib Citrate, Pomalidomide, Dexamethasone, Stem Cell Transplant in Treating Relapsed or Refractory Multiple Myeloma

NCT03202628 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC168ANCI-2017-01145P30CA015083
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well ixazomib citrate, pomalidomide, dexamethasone, and stem cell transplantation works in treating patients with multiple myeloma that has come back or does not respond to treatment. Giving chemotherapy, such as pomalidomide and dexamethasone, before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving ixazomib citrate in addition to pomalidomide, dexamethasone, and stem cell transplantation may work better in treating patients with relapsed or refractory multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival at 18 Months (PFS18) Defined as the Proportion of Patients Alive and Free From Disease Progression at 18 Months From Study Entry

  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. If patients are censored prior to 18 months post registration, a Kaplan Meier (Kaplan, E. and Meier, P., 1958) estimate for PFS18 along with the 95% confidence intervals will be reported.

  18 months

Secondary Outcomes (4)

• Percentage of Participants With Greater Than or Equal to (>=) Very Good Partial Response (VGPR) Rate

  30 months

• Number of Patients Experiencing Adverse Events Graded According to the Medical Dictionary for Regulatory Activities (MedDRA) Version (v) 12.1

  36 months

• Overall Response Rate

  30 months

• Percent of Patients Alive at 30 Months

  30 months

Other Outcomes (2)

• Change in Minimal Residual Disease (MRD) in Bone Marrow Assessed by Flow Cytometry

  Baseline up to 1 year from initiation of maintenance therapy

• Engraftment Kinetics (White Blood Cells [WBC] and Platelet) Following Single Salvage Autologous Stem Cell Transplantation (ASCT)

  Up to 3 years

Study Arms (1)

Treatment (ixazomib, pomalidomide, dexamethasone, ASCT)

EXPERIMENTAL

INDUCTION (COURSES 1-4): Patients receive ixazomib citrate PO on days 1, 8, and 15, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days (courses 1-3) and 56 days (course 4) for up to 4 courses in the absence of disease progression or unacceptable toxicity. TRANSPLANTATION (COURSE 5): Between 2-4 weeks following Induction, patients undergo ASCT. CONSOLIDATION (COURSES 6-9): Beginning 60-120 days following ASCT, patients receive ixazomib citrate, pomalidomide, and dexamethasone as in Induction. Treatment repeats every 28 days (courses 6-8) and 56 days (course 9) for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE (COURSES 10+): Beginning 0-4 weeks following Consolidation, patients receive ixazomib citrate as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Drug: Pomalidomide

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo ASCT

Also known as: autologous stem cell transplantation

Treatment (ixazomib, pomalidomide, dexamethasone, ASCT)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Treatment (ixazomib, pomalidomide, dexamethasone, ASCT)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib, pomalidomide, dexamethasone, ASCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ixazomib, pomalidomide, dexamethasone, ASCT)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst

Treatment (ixazomib, pomalidomide, dexamethasone, ASCT)

Eligibility Criteria

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

You may qualify if:

• Previously treated ASCT naive MM patients, currently with relapsed or refractory disease who are being considered for single ASCT for relapsed disease; patients must be eligible to undergo a stem cell transplant as per institutional criteria for selection at the time of registration
• Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 75 x 10\^9/L unless the participant has \>= 50% bone marrow infiltration in which case a platelet count of \>= 50 x 10\^9/L is allowed
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN) or if total bilirubin is \> 1.5 x ULN, the direct bilirubin must be =\< 2.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN or \< 5 x ULN if liver involvement
• Patients with measurable disease defined as at least one of the following:
• Serum monoclonal protein \>= 1.0 g/dL by protein electrophoresis
• \>= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• Serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Willing to provide informed written consent
• Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
• Willing to follow strict birth control measures

You may not qualify if:

• Diagnosed or treated for another malignancy =\< 2 years prior to registration or previously diagnosed with another malignancy and have any evidence of residual disease
• NOTE: If there is a history or prior malignancy, patient must not be receiving other specific treatment for their cancer; patients with non-melanoma skin cancer or carcinoma in situ of any type, or low-risk prostate cancer after curative therapy, are not excluded if they have undergone complete resection
• NOTE: Platelet transfusions to help patients meet eligibility criteria are not allowed =\< 3 days prior to study registration
• Any of the following:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, 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; NOTE: this includes uncompensated heart or lung disease
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm; NOTE: Bisphosphonates are considered to be supportive care rather than therapy and are allowed while on protocol treatment
• Patient has \>= grade 2 peripheral neuropathy, or grade 1 with pain on clinical examination during the screening period
• Major surgery =\<14 days prior to registration
• Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of Ginkgo biloba or St. John?s wort =\< 14 days prior to registration
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. NOTE: Any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
• Corrected QT (QTc) \> 470 milliseconds (msec) on a 12-lead ECG obtained during the screening period; Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
• Known human immunodeficiency virus (HIV) positive

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; ixazomib; pomalidomide

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Prashant Kapoor
• Organization: Mayo Clinic

Kapoor.Prashant@mayo.edu

507-284-2511

Study Officials

• Prashant Kapoor

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: June 28, 2017
• Study Start: July 24, 2017
• Primary Completion: April 13, 2021
• Study Completion: April 13, 2021
• Last Updated: September 21, 2023
• Results First Posted: May 19, 2022

Record last verified: 2023-09

Locations

US (1)