Horizon Two: High-Risk Newly Diagnosed Multiple Myeloma Study
This study, called Horizon Two, is for people with high-risk newly diagnosed multiple myeloma (a type of blood cancer). It aims to compare different treatment approaches. You might receive a combination of a bispecific monoclonal antibody (Linvoseltamab) and triplet therapy (three drugs), or a monoclonal antibody (Isatuximab-KRd) with an autologous stem cell transplant (using your own stem cells). The study is looking for 300 participants aged 18 or older who have high-risk multiple myeloma, specifically with certain genetic changes like Del(17p) or TP53 mutation. Researchers will measure how well treatments work by looking for sustained measurable residual disease (MRD) negativity after 2 years and how long you live without the disease getting worse (Progression Free Survival) for about 5 years.
- Study design
- This is an interventional, randomized adaptive platform trial, meaning you will be assigned to one of the study treatments by chance. It plans to enroll 300 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will follow participants for Progression Free Survival through study completion, which is roughly 5 years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07053436
Horizon Two: HR NDMM (MMRC-100)
Recruiting
PHASE2Ages 18+InterventionalTreatmentMultiple Myeloma Research ConsortiumGovernment-funded
~300 participants
Updated 2026-06-10 on ClinicalTrials.gov
What's tested:Bispecific Monoclonal Antibody and Triplet TherapyMonoclonal Antibody with Stem Cell Transplant
At a glance
Recruiting sites
7 of 7 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Sustained measurable residual disease (MRD) negativity
Measured over 2 years post randomization
+1 more outcome measured
Conditions
Where it's being run
7 sites across 7 statesGeorgia1
Illinois1
Michigan1
Minnesota1
Missouri1
New York1
North Carolina1
Study leadership
- Hearn Jay Cho, MD, PhD · PRINCIPAL_INVESTIGATOR · Multiple Myeloma Research Foundation
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Voluntarily agree to participate by giving written informed consent
≥18 years of age
Symptomatic and transplant eligible newly diagnosed multiple myeloma histologically confirmed per IMWG criteria that is high-risk as defined by at least one of the following:
Del(17p) (CCF ≥ 20%, by analyses conducted on CD138-positive/purified cells) and/or TP53 mutation assessed by NGS
One of these translocations-t(4;14) or t(14;16) or t(14;20)-co-occurring with +1q and/or del(1p32)
Monoallelic del(1p32) along with +1q, or biallelic del(1p32)
High β2M (≥5.5 mg/dL) with normal creatinine (\<1.2 mg/dL)
Presence of extra-medullary disease non-contiguous with bone at diagnosis (by PET-CT or Whole Body MRI)
Primary plasma cell leukemia (circulating plasma cells \> 5% at diagnosis)
No more than 2 cycles of NCCN listed induction therapy for multiple myeloma
Measurable disease, per IMWG criteria, at time of diagnosis defined as one of the following:
Serum M-protein at diagnosis ≥ 0.5g/dL (0.3 g/dL or above if IgA subtype)
Urine M-protein ≥ 200 mg/24hours
Serum free light chain difference \> 100 mg/L
Plasmacytoma ≥ 2cm
Bone marrow involvement ≥ 30%
ECOG performance status of 0-2
Adequate organ function, as indicated by the following laboratory values:
Adequate hematological function, defined as ANC ≥ 1000/µL, platelet count ≥ 75,000/µL, and hemoglobin ≥ 8 g/dL (transfusion and/or growth factor support is allowed for hematologic parameters as long as the investigator deems the patient otherwise fit for screening)
Adequate hepatic function, defined as total bilirubin level ≤ 1.5 x institutional upper limit of normal (IULN) except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 x IULN is required), AST ≤ 2.5 x IULN, and ALT ≤ 2.5 x IULN
Adequate renal function, defined as calculated creatinine clearance ≥ 30 mL/min per institutional standard (assessment method should be recorded, measured or C-G acceptable)
Persons of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of trial medication). Non-childbearing potential for a person assigned as female at birth is defined as 1 of the following:
≥ 45 years of age and has not had menses for \>1 year
Amenorrheic for \> 2 years without a hysterectomy and/or oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation
Status is post-hysterectomy, -oophorectomy, or -tubal ligation
Persons of childbearing potential must be willing to use highly effective contraceptive measures during sexual contact with a person assigned as male at birth starting with the Screening visit through 90 days after last dose of trial medication.
Note: Abstinence is acceptable if this is the established and preferred contraception for the participant.
Persons assigned as male at birth with a partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the trial starting with the Screening visit through 90 days after the last dose of trial medication is received. Persons assigned as male at birth with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
Note: Abstinence is acceptable if this is the established and preferred contraception method for the participant.
Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using New York Heart Association Functional Classification. To be eligible for this trial, participants should be Class 2 or better. Class 2 is defined as slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest.
Prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of the investigational arms are eligible for this trial.
Known HIV infection and on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated.
History of hepatitis C virus (HCV) infection must have been treated and cured. For patients with known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Willing and able to comply with the requirements of the protocol.
Exclusion
Major concurrent illness or organ dysfunction including but not limited to the following:
POEMS syndrome
Symptomatic major organ involvement AL amyloidosis
History of allergy or known hypersensitivity to any of the trial therapies or any of their excipients, or contraindication to any of the trial therapies as outlined in the local prescribing information (e.g., United States Prescribing Information \[USPI\])
Complete spinal cord compression or CNS involvement
Known leptomeningeal disease
Allogeneic tissue/solid organ transplant recipients with chronic GVHD requiring steroid equivalent dose of \> 20 mg prednisone
Active infection requiring treatment
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
Legally incapacitated or has limited legal capacity
Persons who are pregnant or breastfeeding
What this trial measures
- Sustained measurable residual disease (MRD) negativity2 years post randomization
Sustained MRD negativity is defined as MRD negativity at a minimum threshold of one myeloma cell in one hundred thousand nucleated bone marrow cells at MRD assessments
- Progression Free Survivalthrough study completion, roughly 5 years
PFS is defined as time from randomization to disease progression or death from any cause. Participants who have not progressed or died are censored at the date last known progression-free.