Testing an Experimental Approach to Treat Patients With Plasma Cell Leukemia, The QUANTUM Trial

Inclusion criteria

* Documented diagnosis of primary plasma cell leukemia according to IMWG criteria defined as 5% or greater circulating plasma cells at the time of initial diagnosis * Measurable disease at the time of initial diagnosis of at least one of the following as defined by IMWG criteria: * Serum monoclonal protein ≥ 0.5 g/dL or * Urine monoclonal protein ≥ 200 mg/24 hours (h) or * Serum free light chain (FLC) assay: Serum free light chain ≥ 100 mg/L and abnormal serum free light chain ratio * Age 18 - 80 years * Prior treatment: * ≤ 1 cycle of induction treatment based on physician/investigator discretion * No history of severe allergic reaction (including erythema nodosum) to lenalidomide or other prior immunomodulatory imide drug (IMiD) therapy * No history of clinically significant cardiopulmonary disease resulting from prior proteosome inhibitor therapy * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn, before study entry, the following criteria must be met * Female of childbearing potential (FCBP) is a female who: 1) has achieved menarche (first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries), or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months). \* Female of childbearing potential (FCBP): * Must use a contraceptive method that is highly effective (with a failure rate of \< 1% per year), preferably with low user dependency during the intervention and agrees to not donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention * Given the risk of teratogenicity with immunomodulatory drugs (IMiD), females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to, and again within 24 hours of starting lenalidomide, and must either commit to continued abstinence from heterosexual intercourse or being two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide. Examples of highly effective methods are intrauterine device, hormonal contraceptives, tubal ligation, or partner's vasectomy. Examples of barrier method are male condom, diaphragm, or cervical cap. FCBP must also agree to ongoing pregnancy testing. Men must agree to use latex condom during sexual contract with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum frequency of 28 days about pregnancy precautions and risk of fetal exposure * The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy * Non-childbearing potential is defined as follows (by other than medical reasons): * ≥ 45 years of age and has not had menses for \> 1 year * Patients who have been amenorrhoeic for \< 2 years without history of hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation * Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure * Male patients must agree to use an adequate method of contraception for the duration of the study and for 6 months afterwards. * Male participants: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of altered sperm: * Refrain from donating sperm, PLUS, either: * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR * Must agree to use contraception/barrier as detailed below: * Agree to use a male condom, even if they have undergone successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \< 1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females) * Patients may not have polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, Waldenström's macroglobulinemia, or symptomatic amyloidosis. Amyloidosis found in skin or lymph nodes ("non-vital organs"), or incidental observation of amyloidosis on bone marrow biopsy, are permissible * Clinically significant adverse effects from any prior oncologic treatment (e.g., prior surgery, radiotherapy, or other antineoplastic therapy) must have resolved or have been determined to be clinically stable per the investigator * Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * No patients known to have cardiac risk factors defined by any of the following criteria: * Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block * History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within two (2) months of screening * Class III or IV heart failure as defined by the New York Heart Association functional classification system * Uncontrolled hypertension, defined as persistently elevated blood pressure (BP) meeting Common Terminology Criteria for Adverse Events (CTCAE) version (v) 6.0 for ≥ grade 3 despite medical intervention * Patients with congenital long QT syndrome, Fridericia's formula-corrected QT interval (QTcF) interval QTcF \> 480 msec (the QT interval values must be corrected for heart rate by Fridericia's formula \[QTcF\]) * Left ventricular ejection fraction \< 40% * No significant neuropathy ≥ grade 3 or grade 2 neuropathy with pain at baseline * No known allergies, hypersensitivity, or intolerance to daratumumab and hyaluronidase-fihj, carfilzomib, lenalidomide, or dexamethasone * No known medical condition causing an inability to swallow oral formulations of agents * No major surgery within \< 2 weeks prior to registration or who have not recovered from the side effects of surgery * Contraindication to any concomitant medication, including antivirals or anticoagulation * Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 (or ≥ 500/mm\^3 if due to underlying disease) * Total bilirubin ≤ 2 x upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN) * Calculated (calc.) creatinine clearance ≥ 30 mL/min by Modification of Diet in Renal Disease (MDRD)