Combination treatment for high-risk multiple myeloma

REsponse Adapted Combination Therapy Approaches for High-Risk Multiple Myeloma (REACH)

This study is testing a new combination of cancer drugs to see if it can help people with high-risk multiple myeloma improve their blood test results and fight the disease better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Drugs / interventions: chemotherapy, daratumumab
• Locations: 3 sites (Scottsdale, Arizona and 2 other locations)
• Trial ID: NCT05497804 on ClinicalTrials.gov

What this trial studies

This phase II trial tests the effectiveness of a combination chemotherapy regimen in improving blood test results for patients with high-risk multiple myeloma. The treatment involves administering carfilzomib, daratumumab, lenalidomide, and dexamethasone, which work together to target and eliminate cancer cells. The primary goal is to achieve sustained minimal residual disease negativity, while secondary objectives include assessing treatment response rates and survival outcomes. Additionally, the study will analyze the genetic and environmental factors influencing treatment response.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with newly diagnosed high-risk multiple myeloma and an ECOG performance status of 0 or 1.

Not a fit: Patients with a life expectancy of less than 6 months or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with high-risk multiple myeloma by reducing residual disease and enhancing survival rates.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating multiple myeloma, indicating a potential for success in this approach.

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.
* 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.
* Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum matrix-assisted laser desorption ionization time-of-flight mass-spectrometry \[MASS-FIX\]) at time of diagnosis before induction therapy initiated and available for review to be enrolled. Note: Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained
* 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.
* Left ventricular ejection fraction (LVEF) \>= 40% =\< 30 days prior to pre-registration

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.
* 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.
* Received prior treatment for multiple myeloma prior to pre-registration. Note: results can still be pending as long as the tests have been performed
* 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).
* 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.

Where this trial is running

Scottsdale, Arizona and 2 other locations

• Mayo Clinic in Arizona — Scottsdale, Arizona, United States (Recruiting)
• Mayo Clinic — Jacksonville, Florida, United States (Recruiting)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Shaji K. Kumar, MD — Mayo Clinic in Rochester
• Study coordinator: Clinical Trials Referral Office

Conditions ISS Stage III Plasma Cell Myeloma; Multiple Myeloma