Neoplasms

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Multiple Myeloma

Neoplasms, Plasma Cell

Smoldering Multiple Myeloma

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Dexamethasone

Dexamethasone acetate

Ixazomib

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Patients with high risk SMM will be enrolled on the pilot study and treated with 2 drug combination (Cycles 1-12 Ixazomib at 4 mg weekly on days 1, 8 and 15, and dexamethasone on days 1, 8, 15 and 22 of 28 day cycle); the dexamethasone dose will be 40 mg/week the first 4 cycles, thereafter 20 mg/week.

Ixazomib (MLN9708)

Sham Mailankody, MBBS

The purpose of this study is to see what effects, good and/or bad, the combination of ixazomib and dexamethasone has on the patient and the smoldering multiple myeloma.

Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study

best overall response rate (PR or better) Stringent Complete Response (sCR) Complete Response as defined below plus: Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence (presence/absence of clonal cells is based on the kappa/ lambda ratio. Complete Response (CR) Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow Very Good Partial Response (VGPR) Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24h Partial Response (PR) ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to \<200mg per 24h. If the serum and urine M-protein are unmeasureable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria

Millennium Pharmaceuticals, Inc.

Memorial Sloan Kettering Cancer Center

Amino Acids

Tyrosine Kinase Inhibitors

Ibrutinib

Protein Kinase Inhibitors

Tyrosine

Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis

Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.

Ajai Chari, MD

The purpose of this research study is to test whether the drug ibrutinib (trademark name: IMBRUVICA®) is effective at preventing the development of multiple myeloma in people who currently have smoldering myeloma. The researchers conducting this trial) have reason to believe that ibrutinib can delay the development of multiple myeloma, thus giving people who currently have smoldering myeloma a longer period of time when they feel healthy and well.

Smoldering myeloma is an abnormal condition that is considered to be an early phase of the disease multiple myeloma. In this disorder, there is an abnormal growth of plasma cells, which is a type of blood cell found in the bone marrow. This growth is not as severe in people with smoldering myeloma as it is in multiple myeloma, so people with smoldering myeloma do not have any symptoms and tend to feel well. However, they have a higher risk of developing multiple myeloma than people in the general population.

Some people with smoldering myeloma are at an especially high risk of developing myeloma - 50% of these people will develop multiple myeloma 2 years after they are diagnosed with smoldering myeloma. The investigators identify these people by looking at the amount of myeloma in the bone marrow (called "bone marrow plasma cell percentage") and the amount of myeloma protein (called "serum protein electrophoresis" and "serum free light chain assay") in the blood. To be considered high risk, individuals must have highly abnormal levels for these tests.

Based upon current guidelines, people with smoldering myeloma do not require any treatment. However, known is that many of these people will develop multiple myeloma in the near future. Currently there have been no proven and effective way of preventing these people from developing multiple myeloma, which remains an incurable disease.

This is a phase 2, open-label, single center, prospective pilot study designed to assess the efficacy of ibrutinib in subjects with high risk smoldering multiple myeloma.

All enrolled subjects will be treated with ibrutinib 560 mg (4 capsules, each containing 140 mg) taken PO daily for 12 cycles (28 days each). If a subject demonstrates benefit from ibrutinib, therapy may be extended beyond 12 cycles to a maximum of 2 years. Subjects who progress and meet criteria for symptomatic multiple myeloma will be withdrawn from study.

An initial cohort of 15 subjects will be accrued. If 4 or more patients progress to symptomatic myeloma in one year, then the study will be reviewed with the FDA to determine whether to employ a higher dose of ibrutinib, or to stop for futility. Otherwise, 21 additional patients will be accrued for a total sample size of 36.

Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients

A Phase 2 Study of the Effect of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib on Disease Response in Patients With High Risk Smoldering Multiple Myeloma

Disease response - the proportion of patients with high risk smoldering multiple myeloma who do not progress to symptomatic myeloma as defined by the IMWG.

Overall response rate, defined as partial response or better per IMWG criteria. (IMWG response criteria are - Complete Response, Very good partial response, partial response, Minimal response, stable disease, and progressive disease)

Changes in bone density, particularly in patients with osteopenia (defined as T-score on bone densitometry testing (DEXA) of -1 to -2.5).

Changes in PET-MRI, particularly in patients with osteopenia

Pharmacyclics LLC.

Icahn School of Medicine at Mount Sinai

Associate Professor

Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis

Ibrutinib: Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.

50-59 years old

60 years and older

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Ajai Chari

Number of Patients Without Symptomatic Myeloma

Overall Response Rate

Bone Density Changes

PET-MRI Changes

Change in Serum Interleukin-6 (IL-6)

Change in Serum Stromal Cell-derived Factor-1 (SDF-1)

Change in Serum Receptor Activator of Nuclear-factor Kappa B Ligand (RANKL)

Change in Serum Macrophage Inflammatory Protein-1α (MIP-1α)

Change in Serum Dickkopf-1 (DKK-1)

Change in Serum C-terminal Telopeptide (CTX)

Change in Urine N-terminal Telopeptide (NTx)

Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose taken PO daily for 12 cycles (28 days each).

Ibrutinib: Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study	NCT02697383	Multiple Myelom... High Risk Smold...	Ixazomib (MLN97... Dexamethasone	18 Years -	Memorial Sloan Kettering Cancer Center
Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients	NCT02943473	High Risk Smold...	Ibrutinib	18 Years -	Icahn School of Medicine at Mount Sinai
Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study	NCT02697383	Multiple Myelom... High Risk Smold...	Ixazomib (MLN97... Dexamethasone	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for high risk smoldering multiple myeloma