Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Age 18 years and ≤ 80 years.
  • - High risk smoldering myeloma, which is untreated, as defined by either of the two following criteria: 1.
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% 2. 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.
  • - left ventricular ejection fraction (LVEF) ≥ 40% - LVEF ≥ 40% - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (Appendix VII) - Previously untreated.
  • - Provide informed written consent.
  • - Negative pregnancy test done ≤14 days prior to cycle 1 day 1, for women of childbearing potential only.
  • - All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program and be willing and able to comply with the requirements of the REMS® program.
  • - Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
  • - Willing to follow strict birth control measures as outlined in the protocol.
Female subjects: If they are of childbearing potential, agree to one of the following:
  • - Practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of trial drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR.
  • - Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject.
(Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
  • - Agree to practice effective barrier contraception during the entire trial treatment period and through 90 days after the last dose of trial drug, OR.
  • - Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR.
  • - Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject.
(Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
  • - Willing to return to enrolling institution for follow-up during the Active Treatment Phase of the trial.
  • - Male subjects must agree not to donate sperm for at least 90 days after the last dose of study treatment.
  • - Willing to provide samples for planned research.
  • - Life expectancy > 6 months.
  • - Able to take aspirin (325 mg) daily as prophylactic anticoagulation.
Subjects intolerant to aspirin may use warfarin or low dose molecular weight heparin, novel oral anticoagulants, or low dose molecular weight heparin.

Exclusion Criteria:

  • - 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.
  • - Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • - Prior radiation therapy for bony lesions or plasmacytomas.
  • - Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products.
Known allergies, hypersensitivity, or intolerance to trial drugs.
  • - Inability to comply with protocol/procedures.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03289299
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

International Myeloma Foundation
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Shaji Kumar, MDBrian Durie, MD
Principal Investigator Affiliation Mayo ClinicInternational Myeloma Foundation
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustryIndustryIndustryOther
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Smoldering Multiple Myeloma
Additional Details

This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains incurable with the current approaches. The typical natural history of myeloma is one of repeated relapses, accompanied by genetic evolution and development of new abnormalities, which are often responsible for drug resistance. The presence of a precursor phase of smoldering myeloma, and the ability to identify those at the highest risk of progression, sets the stage to examine the possibility that we can cure the disease through early intervention. In order to potentially achieve this, we need to develop a highly effective combination that includes the most active drugs from different classes. Carfilzomib in combination with lenalidomide and dexamethasone results in high response rates and deep responses in subjects with newly diagnosed myeloma. Daratumumab in combination with lenalidomide results in high response rates in relapsed refractory disease. All these drugs are well tolerated and subjects are able to stay on them long term as a maintenance treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone presents the potential to enhance the effectiveness of the regimens. We hypothesize that this combination will lead to deep response including a higher proportion of minimal residual disease (MRD) negative disease among those with high risk smoldering myeloma and may translate into cure or long term disease quiescence.

Arms & Interventions

Arms

Experimental: Arm A

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

Interventions

Drug: - Carfilzomib

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

Drug: - Lenalidomide

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.

Drug: - Daratumumab

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.

Drug: - Dexamethasone

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Moffitt Cancer Center, Tampa, Florida

Status

Recruiting

Address

Moffitt Cancer Center

Tampa, Florida, 33612

Site Contact

Sabrina Hasan

sabrina.hasan@moffitt.org

813-745-3732

University of Chicago Medical Center, Chicago, Illinois

Status

Recruiting

Address

University of Chicago Medical Center

Chicago, Illinois, 60637

Site Contact

Jennifer Nam

jnam@medicine.bsd.uchicago.edu

773-702-7716

Indiana University Simon Cancer Center, Indianapolis, Indiana

Status

Recruiting

Address

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202

Site Contact

Chelsea Young

youngchs@iu.edu

317-278-5621

University of Kansas Cancer Center, Westwood, Kansas

Status

Recruiting

Address

University of Kansas Cancer Center

Westwood, Kansas, 66205

Site Contact

Kerry Hepler

khepler@kumc.edu

913-945-7552

University of Maryland Medical Center, Baltimore, Maryland

Status

Recruiting

Address

University of Maryland Medical Center

Baltimore, Maryland, 21201

Site Contact

Thea Nash

Thea.Nash@umm.edu

410-328-7680

Mayo Clinic, Rochester, Minnesota

Status

Recruiting

Address

Mayo Clinic

Rochester, Minnesota, 55905

Site Contact

Clinical Trials Referral Office https://www.mayo.edu/research/forms/cancer-clinical-trials

ekim@trevieresearch.com

855-776-0015

Weill Cornell Medicine, New York, New York

Status

Recruiting

Address

Weill Cornell Medicine

New York, New York, 10022

Site Contact

Sheetal Ramnath

shr2026@med.cornell.edu

3235330312

Levine Cancer Institute, Charlotte, North Carolina

Status

Recruiting

Address

Levine Cancer Institute

Charlotte, North Carolina, 28204

Site Contact

Manisha Bhutani, MD

manisha.bhutani@atriumhealth.org

980-442-2000

Swedish Cancer Institute, Seattle, Washington

Status

Recruiting

Address

Swedish Cancer Institute

Seattle, Washington, 98104

Site Contact

Neil Bailey

neil.bailey@swedish.org

206-215-1471

Medical College of Wisconsin, Milwaukee, Wisconsin

Status

Recruiting

Address

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Site Contact

MCW Cancer Center

cccto@mcw.edu

414-805-8900