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Clinical Trial 21551

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT04268498

Phase: Phase II
Principal Investigator: Shain, Kenneth

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or 1-800-679-0775 Learn More

Overview

Study Title

A Phase 2, Open-Label Randomized Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone vs Carfilzomib, Lenalidomide, and Dexamethasone in Patients with Newly-Diagnosed Multiple Myeloma (ADVANCE)

Summary

This study is being done to find out whether carfilzomib, lenalidomide, and dexamethasone (KRD) or KRD and Daratumumab (KRD+DARA) might be safer and more effective ways of controlling multiple myeloma than the stand or care treatment, which is lenalidomide, bortezomib, and dexamethasone (VRD).

Objective

1. To compare the rates of MRD negativity for patients who receive VRD (Arm A) to patients who receive KRD (Arm B) and for patients who receive VRD (Arm A) to patients who received DKRd (Arm C); 2. To compare overall survival, progression-free survival, and event-free survival in patients achieving PR or less within the first 4 cycles of therapy, across the treatment arms (Arm A vs Arm B, Arm A vs Arm C); 3. To compare the rates of PR or better, VGPR or better, CR and sCR across the treatment arms (Arm A vs Arm B, Arm A vs Arm C); 4. To compare the rate of MRD-negativity as a best response after the completion of eight cycles of therapy across the treatment arms (Arm A vs Arm B, Arm A vs Arm C); 5. To compare the safety and tolerability of the three treatment arms; 6. To compare MRD assessments in bone marrow versus blood with different techniques.

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy

Medications

Bortezomib (); CC-5013 (Lenalidomide); Daratumumab (Darzalex); Dexamethasone (); Lenalidomide (Revlimid); PS-341 (Bortezomib); Velcade (Bortezomib); carfilzomib (Kyprolis)

Inclusion Criteria

Inclusion Criteria:

Newly diagnosed patients with histologically confirmed Multiple Myeloma (MM) based on the IMWG diagnostic criteria and measurable disease within the past 4 weeks (or past 8 weeks if patient received pre-study MM therapy) based on one of the following:

Serum monoclonal protein ≥ 1.0 g/dL, Urine monoclonal protein ≥ 200 mg/24 hour, Involved serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal kappa/lambda ratio.

Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following (Note: Myeloma defining event does not need to be based on repeat testing done at screening, if previous pathology, radiology, etc., confirm diagnosis of myeloma per IMWG)

Creatinine Clearance (CrCl) ≥ 60 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method, Modification of Diet in Renal Disease (MDRD), or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae

Age ≥ 18 years at the time of signing the informed consent documentation. Age limit of ≤ 75 years.

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Absolute neutrophil count (ANC) ≥ 1.0 K/microliter (uL), hemoglobin ≥ 8 g/dL, and platelet count ≥ 75 K/uL, unless if cytopenias are deemed to be due disease at discretion of clinical investigator. Transfusions and growth factors are permissible.

Adequate hepatic function

All study participants must be able to tolerate one of the following thromboprophylactic strategies: aspirin, oral facto Xa inhibitors, low molecular weight heparin, warfarin (coumadin), or alternative anti-coagulant.

All study participants must be registered into the mandatory electronic REMS (eREMS) program and be willing and able to comply with the requirements of Risk Evaluation Management and Safety (REMS).

Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin 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. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

Other criteria may apply

Exclusion Criteria

Exclusion Criteria:

Patients receiving >1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma: (a) Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted (b) Bone targeting agents are permitted (c) Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted (d) Prior treatment with radiotherapy is permitted (e) Prior MM treatments, such as Immunomodulating Drugs (IMIDs) or non-MM drugs in clinical trials for smoldering myeloma is permitted with a washout period of 2 weeks from last dose. Smoldering patients previously treated with carfilzomib are excluded.(f) Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 2 weeks from last dose (on a trial or outside a trial) are eligible (Note: Measurable disease is defined as one or more of the following: Serum monoclonal protein ≥ 1.0 g/dL, Urine monoclonal protein ≥ 200 mg/24 hour and/ or Involved serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal kappa/lambda ratio) Prior or current exposure to any of the following: To daratumumab or other anti- Cluster of Differentiation (CD) -38 therapies (unless a re-treatment study). Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer. Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.

Patients with plasma cell leukemia

Patients with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes syndrome (POEMS syndrome)

Patients with amyloidosis

Patients with known Chronic Obstructive Pulmonary Disorder (COPD) with a forced expiratory volume in 1 second (FEV1) > Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.

Pregnant or lactating females. Because there is a potential risk for AEs in nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide, pregnant or lactating females are excluded from study participation. These potential risks may also apply to other agents used in this study.

Uncontrolled hypertension

Uncontrolled diabetes

Active hepatitis B or C infection

Clinically significant cardiac disease.

Pulmonary hypertension

Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting, inflammatory bowel disease, or bowel resection that would prevent absorption of oral agents

Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements

Significant neuropathy ≥ Grade 3 or Grade 2 neuropathy with pain at baseline

Contraindication to any concomitant medication, including antivirals or anticoagulation

Major surgery within 3 weeks prior to first dose

Other exclusions apply

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