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

NCT02655458 | Completed Phase 1 DMC

• 1 other identifier: GCO 15-1275
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Induction Therapy; Autologous Stem Cell Transplant; ASCT; Auto-SCT

Outcome Measures

Primary Outcomes (1)

• Incidence of completion of treatment

  Safety and tolerability will be measured by the number of evaluable patients who complete the treatment protocol.

  up to 24 months

Secondary Outcomes (6)

• IFE level

  up to 24 months

• sFLC level

  up to 24 months

• Bone marrow MRD analysis

  up to 24 months

• Progression-Free Survival

  up to 24 months

• CyTOF mass cytometry

  up to 24 months

Study Arms (1)

autologous PBMC reconstitution, Elotuzumab, Lenalidomide

EXPERIMENTAL

Max number of cycles is 12. Elotuzumab will be administered IV 20 mg/kg on Day 1 of each cycle. Lenalidomide dosing will start with cycle 4 at 10 mg orally daily days 1-21.

Drug: Elotuzumab; Drug: Lenalidomide; Other: autologous PBMC reconstitution; Other: ASCT

Interventions

Elotuzumab DRUG

The following must also be administered before any elotuzumab: Dexamethasone 8 mg IV (on the day of elotuzumab infusion 45-90 mins prior to the start of infusion), the following 30 - 90 minutes prior to start of infusion: H1 blocker: diphenhydramine (25 - 50 mg po or IV) or equivalent, H2 blocker: ranitidine (50 mg IV) or equivalent (adjusted for renal failure as indicated), acetaminophen (650 - 1000 mg po).

Also known as: Empliciti

autologous PBMC reconstitution, Elotuzumab, Lenalidomide

Lenalidomide DRUG

On the days of elotuzumab administration, the dose of lenalidomide is to be administered at least 2 hours after completion of elotuzumab dosing. Aspirin 81 mg PO daily will also be prescribed for DVT prophylaxis.

Also known as: Revlimid

autologous PBMC reconstitution, Elotuzumab, Lenalidomide

autologous PBMC reconstitution OTHER

Autologous peripheral blood mononuclear cell collection and reconstitution. PBMC will be collected from patients by standard apheresis procedures. Up to 25 ml of autologous plasma will also be recovered for dilution of cryopreserved products (if necessary). For reconstitution, Patients will be pre-medicated as per each institution's standard protocols prior to reinfusion of PBMC products. Patient ID will be checked and verified by nursing staff and the products will be re-infused by continuous intravenous infusion pump. Patient vital signs will be monitored every 15 minutes for the duration of the procedure as per standard reinfusion protocol.

autologous PBMC reconstitution, Elotuzumab, Lenalidomide

ASCT OTHER

Autologous peripheral blood stem cell transplantation. (stem cells from the patient's own marrow are "harvested," stored and then returned to the body (engrafted). To be done as part of standard of care.

Also known as: auto-SCT consolidation therapy

autologous PBMC reconstitution, Elotuzumab, Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Known or suspected cardiac amyloidosis
• Congestive heart failure of Class III or IV of the NYHA classification
• Uncontrolled angina, hypertension or arrhythmia
• Myocardial infarction in the past 6 months
• Any uncontrolled or severe cardiovascular disease
• Prior cerebrovascular event with persistent neurologic deficit.
• Known HIV Infection or active hepatitis A, B or C.

Sponsors & Collaborators

• Hearn Jay Cho: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• Coffey DG, Osman K, Aleman A, Bekri S, Kats S, Dhadwal A, Catamero D, Kim-Schulze S, Gnjatic S, Chari A, Parekh S, Jagannath S, Cho HJ. Phase 1 study combining elotuzumab with autologous stem cell transplant and lenalidomide for multiple myeloma. J Immunother Cancer. 2024 Apr 12;12(4):e008110. doi: 10.1136/jitc-2023-008110.

  PMID: 38609316 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

elotuzumab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hearn Jay Cho, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: January 14, 2016
• Study Start: January 1, 2016
• Primary Completion: July 13, 2017
• Study Completion: July 13, 2017
• Last Updated: August 18, 2017

Record last verified: 2017-08

Locations

US (1)