Trial Title:
Combination Treatment Therapy Approaches for the Treatment of High-Risk Multiple Myeloma, REACH Trial
NCT ID:
NCT05497804
Condition:
ISS Stage III Plasma Cell Myeloma
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Dexamethasone acetate
Lenalidomide
Daratumumab
Ichthammol
BB 1101
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration and Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (combination chemotherapy)
Intervention type:
Drug
Intervention name:
Carfilzomib
Description:
Given IV
Arm group label:
Treatment (combination chemotherapy)
Other name:
Kyprolis
Other name:
PR-171
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (combination chemotherapy)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Daratumumab
Description:
Given SC
Arm group label:
Treatment (combination chemotherapy)
Other name:
Darzalex
Other name:
HuMax-CD38
Other name:
JNJ-54767414
Other name:
Daratumumab Biosimilar HLX15
Other name:
Daratumumab-fihj
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Given IV/PO
Arm group label:
Treatment (combination chemotherapy)
Other name:
Aacidexam
Other name:
Adexone
Other name:
Aknichthol Dexa
Other name:
Alba-Dex
Other name:
Alin
Other name:
Alin Depot
Other name:
Alin Oftalmico
Other name:
Amplidermis
Other name:
Anemul mono
Other name:
Auricularum
Other name:
Auxiloson
Other name:
Baycadron
Other name:
Baycuten
Other name:
Baycuten N
Other name:
Cortidexason
Other name:
Cortisumman
Other name:
Decacort
Other name:
Decadrol
Other name:
Decadron
Other name:
Decadron DP
Other name:
Decalix
Other name:
Decameth
Other name:
Decasone R.p.
Other name:
Dectancyl
Other name:
Dekacort
Other name:
Deltafluorene
Other name:
Deronil
Other name:
Desamethasone
Other name:
Desameton
Other name:
Dexa-Mamallet
Other name:
Dexa-Rhinosan
Other name:
Dexa-Scheroson
Other name:
Dexa-sine
Other name:
Dexacortal
Other name:
Dexacortin
Other name:
Dexafarma
Other name:
Dexafluorene
Other name:
Dexalocal
Other name:
Dexamecortin
Other name:
Dexameth
Other name:
Dexamethasone Intensol
Other name:
Dexamethasonum
Other name:
Dexamonozon
Other name:
Dexapos
Other name:
Dexinoral
Other name:
Dexone
Other name:
Dinormon
Other name:
Dxevo
Other name:
Fluorodelta
Other name:
Fortecortin
Other name:
Gammacorten
Other name:
Hemady
Other name:
Hexadecadrol
Other name:
Hexadrol
Other name:
Lokalison-F
Other name:
Loverine
Other name:
Methylfluorprednisolone
Other name:
Millicorten
Other name:
Mymethasone
Other name:
Orgadrone
Other name:
Spersadex
Other name:
TaperDex
Other name:
Visumetazone
Other name:
ZoDex
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Given PO
Arm group label:
Treatment (combination chemotherapy)
Other name:
CC-5013
Other name:
CC5013
Other name:
CDC 501
Other name:
Revlimid
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (combination chemotherapy)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET
Arm group label:
Treatment (combination chemotherapy)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA scan
Arm group label:
Treatment (combination chemotherapy)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Summary:
This phase II trial test whether combination chemotherapy works to improve blood test
results in patients with high-risk multiple myeloma. Chemotherapy drugs, such as
carfilzomib, daratumumab, lenalidomide, and dexamethasone, work in different ways to stop
the growth of cancer cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. This trial may help determine if patients who have a
small amount of cancer left after the initial treatment, called minimal residual disease,
will benefit from the drug combination.
Detailed description:
PRIMARY OBJECTIVE:
I. To estimate the rate of sustained minimal residual disease (MRD) negativity (MRD
negative status at any point, with a repeated MRD negative status one year later) in
subjects with high-risk multiple myeloma.
SECONDARY OBJECTIVES:
I. To describe the toxicities associated with this treatment approach in subjects with
high-risk multiple myeloma (MM).
II. To estimate the overall response rate, very good partial response (VGPR) or better
rate and complete response (CR) rate at the end of induction, end of consolidation, end
of maintenance and at two years after the completion of treatment.
III. To estimate the progression-free survival and overall survival rate.
CORRELATIVE RESEARCH OBJECTIVES:
I. To describe the clonal architecture through a combination of genomic, epigenomic,
proteomic and metabolomic studies before and after treatment, in subjects with high-risk
MM.
II. To describe the bone marrow microenvironment through various stages of treatment and
the time of MRD negative state and at time of relapse.
OUTLINE:
INDUCTION: Patients receive carfilzomib intravenously (IV) on days 1, 2, 8, and 15 of
cycle 1 and days 1, 8, and 15 of cycles 2-12, lenalidomide orally (PO) days 1-21 of each
cycle, daratumumab subcutaneously (SC) days 1, 8, 15, and 22 of cycles 1 and 2, days 1
and 15 of cycles 3-6, and day 1 of subsequent cycles, and dexamethasone PO or IV on days
1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for 12 cycles in the
absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive carfilzomib IV on days 1, 8, and 15, lenalidomide PO days
1-21, daratumumab SC day 1 of each cycle. Treatment repeats every 28 days for 12 cycles
in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive carfilzomib IV on day 1, lenalidomide PO days 1-21,
daratumumab day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the
absence of disease progression or unacceptable toxicity.
Patients undergo magnetic resonance imaging (MRI) and computed tomography/positron
emission tomography(CT/PET) during screening. Patients also undergo bone marrow aspirate
and biopsy, blood sample collection, and echocardiography (ECHO) or multigated
acquisition (MUGA) scan throughout the study.
After completion of study treatment, patients are followed up every 6 months for up to10
years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- PRE-REGISTRATION-INCLUSION CRITERIA:
- Age >= 18 years and =< 80 years.
- Patient must have suspected or confirmed newly diagnosed multiple myeloma by
International Myeloma Working Group (IMWG) criteria.
- Left ventricular ejection fraction (LVEF) >= 40% =< 30 days prior to
pre-registration.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
- Provide informed written consent.
- Willing to return to enrolling institution for follow-up during the active treatment
phase of the trial.
- Willing to provide blood and bone marrow samples for planned research.
- Life expectancy > 6 months.
- Able to take aspirin (325 mg) daily as prophylactic anticoagulation.
- Note: subjects intolerant to aspirin may use warfarin, novel oral
anticoagulants, or low dose molecular weight heparin.
- REGISTRATION-INCLUSION CRITERIA:
- High risk myeloma, which is untreated, defined as any two of:
- Beta-2 microglobulin >5.5
- Gain or amplification of chr1q
- del17p or monosomy 17 or TP53 mutation (if known)
- t(4;14) or t(14;16)
- >= 5% circulating plasma cells
- presence of extramedullary disease (does not include bone contiguous disease)
- Creatinine clearance >= 30 mL/min (using Cockroft-Gault equation) (obtained =< 14
days prior to registration).
- Absolute neutrophil count (ANC) >= 1000/mm^3 (without the use of growth factors)
(obtained =< 14 days prior to registration).
- Platelet count >= 75000/mm^3 (obtained =< 14 days prior to registration).
- Hemoglobin >= 8.0 g/dL.
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to
registration).
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (obtained
=< 14 days prior to registration).
- Registration must be completed =< 30 days after pre-registration.
- Patients must not have received more than one cycle of treatment between
pre-registration and registration.
- All 4 drugs in the study regimen approved by insurance.
Exclusion Criteria:
- PRE-REGISTRATION EXCLUSION:
- Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, light
chain amyloidosis with organ involvement.
- Diagnosed or treated for another malignancy =< 1 year prior to pre- registration 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.
- 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: Concurrent chemotherapy is any treatment not related to multiple myeloma.
- NOTE: Concurrent chemotherapy is any treatment not related to multiple myeloma
- 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 =< 30
days prior to registration.
- Major surgery =< 14 days prior to pre-registration.
- 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 electrocardiogram (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)
deoxyribonucleic acid (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.
- 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.
- REGISTRATION-EXCLUSION CRITERIA:
- 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).
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Lief Bergsagel, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Sikander Ailawadhi, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trial Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Shaji K. Kumar, M.D.
Email:
Principal Investigator
Start date:
September 22, 2022
Completion date:
November 20, 2028
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05497804
https://www.mayo.edu/research/clinical-trials
