Overview

A Study of Daratumumab in Patients With Newly Diagnosed Multiple Myeloma

Status:
Active, not recruiting
Trial end date:
2022-09-01
Target enrollment:
0
Participant gender:
All
Summary
This is a study to test the safety and effectiveness of the study drug, daratumumab in combination with carfilzomib, lenalidomide and dexamethasone. The purpose of this study is to test whether giving daratumumab along with the other drugs (carfilzomib, lenalidomide and dexamethasone) is safe for patients.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Memorial Sloan Kettering Cancer Center
Collaborator:
Janssen Pharmaceuticals
Treatments:
Antibodies, Monoclonal
BB 1101
Daratumumab
Dexamethasone
Dexamethasone acetate
Lenalidomide
Thalidomide
Criteria
Inclusion Criteria:

- Newly diagnosed patients with histologically confirmed MM based on the following
criteria:

- Clonal plasma cells in the bone marrow

- Measurable disease within the past 4 weeks defined by any 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:

- Hypercalcemia: serum calcium >0.25 mmol/L (> 1 mg/dL) above upper limit of normal
or ≥ 2.75 mmol/L (11 mg/dL)

- Anemia: hemoglobin value <10 g/dL or > 2 g/dL below lower limit of normal

- Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or PET-CT. For patients
with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells

- Clonal bone marrow plasma cell percentage ≥60%

- Involved/un-involved serum free light chain ratio ≥100 and involved free light
chain >100 mg/L.

- 1 focal lesion on magnetic resonance imaging study (lesion must be >5 mm) in
size

- Creatinine Clearance ≥ 60 ml/min. CrCl can be measured or estimated using
Cockcroft-Gault method, MDRD, or CKD-EPI formulae

- Age ≥ 18 years at the time of signing the informed consent documentation

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil
count (ANC) ≥ 1.0 K/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, with bilirubin < 1.5 x the ULN, and AST and ALT < 3.0 x
ULN.

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

- All study participants must be registered into the mandatory eREMS® program, and be
willing and able to comply with the requirements of 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.

- A female of childbearing potential is a sexually mature female who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding 24 consecutive months).

Exclusion Criteria:

- Patients receiving >1 cycle of prior treatment or concurrent systemic treatment for
multiple myeloma

- Treatment of hypercalcemia or spinal cord compression or aggressively progressing
myeloma with current or prior corticosteroids is permitted

- Bisphosphonates are permitted

- Concurrent or prior treatment with corticosteroids for indications other than
multiple myeloma is permitted

- Prior treatment with radiotherapy is permitted

- Prior treatment for smoldering myeloma is permitted with a washout period of 2
weeks from last dose. Smoldering patients previously treated with carfilzomib are
excluded.

- 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

- Plasma cell leukemia

- POEMS syndrome

- Amyloidosis

- Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1
second (FEV1) <50% of predicted normal (note that FEV1 testing is required for
subjects suspected of having chronic obstructive pulmonary disease and subjects must
be excluded if FEV1 <50% of predicted normal).

- Pregnant or lactating females. Because there is a potential risk for adverse events
nursing infants secondary to treatment of the mother with carfilzomib in combination
with lenalidomide. These potential risks may also apply to other agents used in this
study.

- Uncontrolled hypertension or diabetes

- Active hepatitis B or C infection

- Subject is:

- Seropositive for human immunodeficiency virus (HIV)

- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (i.e., 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) 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.*

- Seropositive for hepatitis C (except in the setting of a sustained virologic
response [SVR], defined as aviremia at least 12 weeks after completion of
antiviral therapy).

- Has significant cardiovascular disease with NYHA Class III or IV symptoms, EF<40% or
hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction
within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as
determined by history and physical examination. Echocardiogram will be performed
during screening evaluation.

- Pulmonary hypertension

- Has refractory 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