Overview

Elotuzumab in Autologous Stem Cell Transplantation (ASCT) and Lenalidomide Maintenance for Multiple Myeloma

Status:
Completed
Trial end date:
2017-07-13
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to explore the combination of Elotuzumab in combination with autologous stem cell transplantation and lenalidomide maintenance to see what side effects it may have and how well it works for the treatment of symptomatic multiple myeloma diagnosed and treated with induction therapy in the past year. Induction therapy is the first phase of treatment for multiple myeloma. The goal of induction therapy for multiple myeloma is to reduce the number of plasma cells in the bone marrow and the proteins that the plasma cells produce. Induction therapy is usually given for 3-4 weeks. An autologous peripheral blood stem cell transplant is a procedure in which immature "stem cells" are collected and stored for future use. A high dose of chemotherapy is given to the patient to destroy myeloma cells, and the patient's stem cells are replaced. The investigational drug in this program is elotuzumab. Elotuzumab is known as BMS-901608. Elotuzumab is a manufactured protein directed against a target found on multiple myeloma cells. Lenalidomide is currently approved for patients with multiple myeloma. Melphalan and cyclophosphamide, the drugs used during stem cell collection and transplant, are also approved by the U.S. FDA. Melphalan is an FDA-approved chemotherapy for multiple myeloma and is used as high-dose treatment prior to stem cell transplantation. Cyclophosphamide is an FDA-approved chemotherapy that may be used, either alone, or in combination with other drugs to treat multiple myeloma.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hearn Jay Cho
Collaborator:
Bristol-Myers Squibb
Treatments:
Elotuzumab
Lenalidomide
Thalidomide
Criteria
Inclusion Criteria:

- Subject is, in the investigator's opinion, willing and able to comply with the
protocol requirements.

- Subject has given voluntary written informed consent before performance of any
study-related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the subject at any time without prejudice to their future
medical care.

Target Population

- Subjects with symptomatic MM by IMWG criteria who are receiving or have completed
induction chemotherapy, who have achieved at least a PR on most recent therapy by IMWG
criteria, and are eligible for auto-SCT for consolidation. A specific induction
regimen is not dictated for this protocol, however, the induction regimen must not
have contained melphalan (L-PAM, Alkeran).

- Age > 18 years or legal age of consent per local regulations.

- Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.

- Documented evidence of newly diagnosed, symptomatic MM, by IMWG criteria within one
year of enrollment

- Prior lenalidomide exposure is permitted only if the subject did not discontinue
lenalidomide due to a related, grade ≥ 3 AE. Age and Reproductive Status

- Men and women of childbearing potential (WOCBP) must be using 2 reliable methods of
contraception to avoid pregnancy throughout the study for a period of at least 30 days
before and 90 days after the last dose of investigational product in such a manner
that the risk of pregnancy is minimized. See Section 4.3.3 for the definition of WOCBP
and also refer to the Revlimid Risk Management Plan guidelines.

- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
or equivalent units of HCG). The first should be performed within 10 to 14 days and
the second within 24 hours prior to the start of the study drug. A prescription for
lenalidomide for a female of childbearing potential must not be issued by the
prescriber until negative pregnancy tests have been verified by the prescriber.

- Women must not be breastfeeding.

- Men must agree to use a latex condom and a second form of birth control during sexual
contact with WOCBP, even if they have had a successful vasectomy, and must agree not
to donate sperm during study drug therapy and for 90 days after therapy.

- Subjects must be willing to refrain from blood donations during study drug therapy and
for 8 weeks after therapy.

Exclusion Criteria:

Target Disease

- MGUS, Waldenström's macroglobulinemia, or asymptomatic (smoldering) myeloma.

- Active plasma cell leukemia (defined as either 20% of peripheral white blood cells
comprised of plasma/CD138+ cells or an absolute plasma cell count of 2 x 109/L).

Medical History and Concurrent Diseases

- All AEs of any prior chemotherapy, surgery, or radiotherapy not resolved to National
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v.4.0)
Grade ≤ 2.

- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes).

- Acute renal failure due solely to readily reversible causes such as hypercalcemia,
hyperuricemia, dehydration, hyperviscosity, or acute tubular necrosis from nephrotoxic
drugs.

- Significant cardiac disease as determined by the investigator including:

1. Known or suspected cardiac amyloidosis

2. Congestive heart failure of Class III or IV of the NYHA classification

3. Uncontrolled angina, hypertension or arrhythmia

4. Myocardial infarction in the past 6 months

5. Any uncontrolled or severe cardiovascular disease

- Prior cerebrovascular event with persistent neurologic deficit.

- Known HIV Infection or active hepatitis A, B or C.

- Any medical conditions that, in the investigator's opinion, would impose excessive
risk to the subject.

Examples of such conditions include:

a. Any uncontrolled disease, such as pulmonary disease, infection, seizure disorder b. Any
altered mental status or any psychiatric condition that would interfere with the
understanding of the informed consent c. Active infection that requires parenteral
anti-microbial or anti-parasitic treatment

- Prior or concurrent malignancy, except for the following:

1. Adequately treated basal cell or squamous cell skin cancer;

2. Or any other cancer from which the subject has been disease-free for > 5 years

- Uncontrolled diabetes (defined as Hgb A1C > 8.0%)

- Unable to tolerate thromboembolic prophylaxis including, as clinically indicated,
aspirin, Coumadin (warfarin) or dose adjusted low-molecular weight heparin. Physical
and Laboratory Test Findings

- Corrected serum calcium > 11.5 mg/dl within 2 weeks of enrollment.

- Absolute neutrophil count < 1000 cells/mm3. No granulocyte colony stimulating factors
(G-CSF or GMCSF) allowed within 1 week of enrollment. No pegylated granulocyte colony
stimulating factors are allowed within 3 weeks of treatment start.

- Platelets < 75,000 cell/mm3 (75 x 109/L). Qualifying laboratory value must occur at
most recent measurement before enrollment and must be no more than 14 days before
enrollment. No transfusions are allowed within 72 hours before qualifying laboratory
value.

- Hemoglobin < 8 g/dL. Qualifying laboratory value must occur at most recent measurement
before enrollment and must be no more than 14 days before enrollment. No transfusions
are allowed within 72 hours before qualifying laboratory value.

- Total bilirubin > 2X ULN ,or direct bilirubin > 2.0 mg/dL.(except patients with
Gilbert's syndrome then total bilirubin >2X ULN allowed in the absence of other
hepatic signs or symptoms)

- AST or ALT > 3X ULN.

- CrCl < 60 ml/min by Cockcroft-Gault Formula Prior Therapy or Surgery

- Major surgery within 3 weeks prior to treatment.

- Kyphoplasty or vertebroplasty within 1 week of enrollment.

- Prior allogeneic stem cell transplant

- Treatment with plasmapheresis within 4 weeks before enrollment.

- Prior therapy with elotuzumab or any IMiD (including pomalidomide), except for prior
thalidomide or lenalidomide (as defined in inclusion criteria).

- NSAIDs, IV contrast, aminoglycosides, or other potentially nephrotoxic drugs within 2
weeks of enrollment.

- Steroids within 3 weeks of enrollment, except:

1. ≤ 10 mg prednisone or equivalent per day

2. Steroid with little to no systemic absorption (ie, topical or inhaled steroids)
Allergies and Adverse Drug Reaction

- Known hypersensitivity to lenalidomide, dexamethasone, any excipients in the
elotuzumab formulation (sodium citrate, citric acid, sucrose and polysorbate 80) or
recombinant protein.

- History of Grade 4 rash associated with thalidomide treatment. Sex and Reproductive
Status

- Women of childbearing potential (WOCBP) who are pregnant or lactating or unwilling to
use 2 forms of effective birth control.

- Men who are fertile and sexually active unwilling to use 2 forms of effective birth
control if their partners are WOCBP. Other Exclusion Criteria

- Prisoners or subjects who are involuntarily incarcerated.

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.