Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant

NCT03289299 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: BS0012015941754767414MMY2009RV-CL-MM-IMF-008479
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 10

Brief Summary

This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each cycle is 28 days.

Conditions

Smoldering Multiple Myeloma

Keywords

myeloma; MRD; smoldering

Outcome Measures

Primary Outcomes (1)

• Stringent complete response rate

  A confirmed sCR on 2 consecutive evaluations at any time during the course of treatment.

  During treatment

Secondary Outcomes (5)

• MRD negativity after each treatment phase

  6 months, 12 months, and 2 years

• MRD negativity at 1 year post treatment

  1 year post treatment

• Overall Survival

  up to 10 years post registration

• Progression-free survival

  up to 10 years post registration

• Adverse events

  2 years

Study Arms (1)

Arm A

EXPERIMENTAL

Non-high dose treatment in 3 phases Induction 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Consolidation 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Maintenance 12 cycles: lenalidomide, daratumumab

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Daratumumab; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

56 mg/m2 IV given on days 1, 8, and 15 of each cycle during induction and consolidation phases of the study.

Arm A

Lenalidomide DRUG

25 mg po given on days 1-21 of each cycle during the induction and consolidation phases. 10 mg po given on days 1-21 of each cycle during the maintenance phase.

Arm A

Daratumumab DRUG

16 mg/kg IV given on days 1, 8, 15, and 22 of cycles 1-2; days 1 and 15 of cycles 3-6; day 1 of cycle 7-12; Day 1 of odd cycles for cycles 13-24.

Arm A

Dexamethasone DRUG

40 mg oral given on days 1, 8, 15, and 22 of cycles 1-6 20 mg oral given on days 1, 8, 15, and 22 of cycles 7-12

Arm A

Eligibility Criteria

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

You may qualify if:

• Age 18 years and ≤ 80 years
• High risk smoldering myeloma, which is untreated, as defined by either of the two following criteria:
• Presence of any two of the following: Serum M spike \> 2 gm/dL OR an involved to uninvolved free light chain (FLC) ratio \> 20 OR bone marrow PC% \> 20%
• Total score of 9 or above using the following scoring system:
• FLC Ratio \>10-25 = 2 \>25-40 = 3 \> 40 = 5
• Serum M Protein (g/dL) \>1.5-3 = 3 \>3 = 4
• BMPC% \>15-20 = 2 \>20-30 = 3 \>30-40 = 5 \>40 = 6
• FISH abnormality (t(4,14), t(14,16), 1q gain, or del13q = 2
• The following laboratory values obtained 14 days prior to registration.
• Calculated creatinine clearance (using Cockcroft-Gault equation below)\* ≥ 30 mL/min
• Absolute neutrophil count (ANC) ≥ 1000/mm3 (without the use of growth factors)
• Platelet count ≥ 75000/mm3
• Hemoglobin ≥8.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN

You may not qualify if:

• monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, active myeloma by current IMWG definition, light chain amyloidosis with organ involvement or patients with extramedullary disease.
• Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception (per protocol)
• Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease.
• Other concurrent chemotherapy, or any ancillary therapy considered investigational. NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.
• Peripheral neuropathy ≥ Grade 3 on clinical examination or grade 2 with pain within 30 days prior to C1D1.
• Major surgery ≤14 days prior to C1D1.
• Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• New York Heart Association (NYHA) II, III, IV heart failure
• Known human immunodeficiency virus (HIV) positive.
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Known or suspected active hepatitis C infection.

Sponsors & Collaborators

• International Myeloma Foundation: lead
• Amgen: collaborator
• Janssen Scientific Affairs, LLC: collaborator
• Celgene: collaborator
• Trevie, Inc.: collaborator

Study Sites (10)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Weill Cornell Medicine

New York, New York, 10022, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

carfilzomib; Lenalidomide; daratumumab; Dexamethasone

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Shaji Kumar, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Brian Durie, MD

  International Myeloma Foundation

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles).

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: September 20, 2017
• Study Start: May 25, 2018
• Primary Completion: September 26, 2023
• Study Completion (Estimated): November 15, 2031
• Last Updated: December 12, 2023

Record last verified: 2023-12

Locations

US (10)