2015-12: A Study Exploring the Use of Early and Late Consolidation/Maintenance Therapy

Past studies conducted at the Myeloma Institute and at other institutions have shown that
many patients with high-risk disease (as determined by gene array studies - studies that look
at specific genes using special equipment) tend to have shorter remissions (disappearance of
signs and symptoms of myeloma) and do not survive as long as participants with low-risk
myeloma. The Total Therapy approach to treatment carried out at the Myeloma Institute where
multiple chemotherapy agents are given as induction followed by a stem cell transplant,
post-transplant consolidation, and maintenance therapy has proven to be the best available
treatment strategy. However, the availability of new treatments that work in different ways
offers the possibility of improving the effectiveness of Total Therapy treatment while
potentially reducing the number of side effects patients' experience. Daratumumab is a human
monoclonal antibody or protein drug. It recognizes a specific protein, CD38, which is found
at high levels on multiple myeloma cells. An antibody is something that finds and kills
foreign objects in your body, in this case, myeloma cells. The other drugs that will be used
in the study treatment regimen include carfilzomib or bortezomib, thalidomide, lenalidomide,
dexamethasone, cisplatin, adriamycin, cyclophosphamide, etoposide, lenalidomide and
dexamethasone.

Inclusion Criteria:

- Patients must have newly diagnosed active Multiple Myeloma (MM) requiring treatment.
Patients with a previous history of smoldering myeloma will be eligible if there is
evidence of progressive disease requiring chemotherapy.

- Patients must be either untreated or have not received more than four cycles of
systemic MM therapy (e.g. Revlimid Dexamethasone (RD), Bortezomib Revlimid
Dexamethasone (VRD). Prior bisphosphonates and localized radiation are allowed.

- Participants must have high-risk disease, as defined by at least one of the following:

- Myeloma Prognostic Risk Signature (MyPRS) risk score ≥ 50.4

- Lactate Dehydrogenase (LDH) ≥ 360 U/L (Rule out hemolysis and infection; contact PI if
any doubt.)

- Diagnosis of primary plasma cell leukemia.

- Eastern Cooperative Oncology Group (ECOG) ≤ 2, unless solely due to symptoms of
MM-related bone disease.

- Patients must have a platelet count ≥ 50,000/μL, unless lower levels are explained by
extensive bone marrow plasmacytosis.

- Patients must be at least 18 years of age and not older than 75 years of age at the
time of registration.

- Participants must have a baseline serum creatinine level < 3 mg/dL and baseline
Alanine Aminotransferase (ALT) < 3x Upper Limit of Normal (ULN).

- Participants must have an ejection fraction by echocardiogram (ECHO) or Multiple-gated
Acquisition Scan (MUGA) scan ≥ 45%

- Patients must have adequate pulmonary function studies > 50% of predicted on
mechanical aspects (Forced Expiratory Volume 1 (FEV1), Forced Vital Capacity (FVC) and
diffusion capacity (DLCO) > 50% of predicted. If the patient is unable to complete
pulmonary function tests due to MM related pain or other conditions, an exception may
be granted if the principal investigator documents that the patient is a candidate for
high dose therapy.

- Patients must have signed an Institutional Review Board (IRB)-approved informed
consent indicating their understanding of the proposed treatment and that the protocol
has been approved by the Institutional Review Board (IRB).

Exclusion Criteria:

- No evidence of high-risk disease

- Poorly controlled hypertension, diabetes mellitus, active or uncontrolled hepatitis,
or other serious medical or psychiatric illness that could potentially interfere with
the completion of treatment according to this protocol.

- Patients must not have prior malignancy, except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
patient has not received treatment for one year prior to enrollment. Other cancers
will only be acceptable if the patient's life expectancy exceeds five years.

- Pregnant or nursing women may not participate. Women of childbearing potential must
have a negative pregnancy documented within one week of registration.

- Subjects of reproductive potential may not participate unless they have agreed to use
an effective contraceptive method.