Combination Study for High Risk Multiple Myeloma Patients

NCT03104270 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CA204-187
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 6

Brief Summary

Despite the recent introduction of novel anti-multiple myeloma (MM) agents, high risk MM remains with poor prognosis and a therapeutic challenge. Elotuzumab (ELO) is a humanized monoclonal antibody that recognizes CS1/CD139, a molecule highly expressed in MM cells. The ELO (10 mg/kg), lenalidomide (LEN) and dexamethasone (DEX) combination achieves high overall response rates (ORR) and long progression-free survival (PFS) for patients with relapsed/refractory disease (RR) MM and those with impaired renal function. However, its efficacy for MM patients with high risk characteristics is still unknown. Pomalidomide (POM) is a recently approved immunomodulatory agent (IMiD) that produces response rates for high-risk RRMM patients when used in combination with DEX and other agents, including the proteasome inhibitor (PI) bortezomib (BTZ). POM has also demonstrated activity for LEN refractory patients. Carfilzomib (CFZ) is a potent second generation PI that has shown to be efficacious for IMiD and BTZ refractory patients as well as high risk patients carrying cytogenetic abnormalities. In this study, we propose to evaluate efficacy and safety of ELO in combination with POM, DEX and CFZ for high-risk RRMM patients.

Conditions

Multiple Myeloma

Keywords

Elotuzumab, Multiple Myeloma, Phase 2

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria (If necessary re-define MTD via the number of dose-limiting toxicities (DLTs) per dose level, of elotuzumab in combination with pomalidomide, carfilzomib and dexamethasone for high risk RRMM patients (based on six patients lead-in cohort if necessary).

  34 Months

• Overall Rate of Response (Efficacy)

  Efficacy of treatment will be assessed by the Overall response rate (ORR) \[ORR=complete response (CR†) + very good partial response (VGPR) + partial response (PR)\] Clinical benefit rate (CBR) \[CBR=CR† + VGPR + PR + minor response (MR)\].

  34 Months

Secondary Outcomes (3)

• PFS

  34 Months

• DOR

  34 Months

• OS

  34 Months

Study Arms (1)

Elo Pom Car and Dex

EXPERIMENTAL

Drug dosing and administration: All drugs are administered on a 28-day cycle. Elotuzumab: 10 mg/kg IV on Days 1,8,15 and 22 Cycles 1 and 2. 20 mg/kg on Day 1 of Cycles 3 and beyond. Pomalidomide: 3 mg PO on days 1-21 Carfilzomib: 20 mg/m2 IV on days 1 of cycle 1. 56 mg/m2 IV on days 8 and 15 of cycle 1 and Days 1, 8 and 15 of the remaining seven cycles. Dexamethasone: On days 1,8,15,22 of Cycle 1-2 and day 1 of Cycle 3 and every day 1 thereafter, pre-treatment with 28 mg PO 3-24 hours prior to the start of ELO. On days 8,15,22 of Cycle 3 and beyond, 40mg of DEX PO or IV. On Day 8 and 15 of Cycle 3 and beyond, pre-treatment with DEX 40mg PO or IV at least 30 min and no more than 4 hours prior to the start of CFZ.

Drug: Elotuzumab; Drug: Pomalidomide; Drug: Carfilzomib; Drug: Dexamethasone

Interventions

Elotuzumab DRUG

Elotuzumab IV at 10mg/kg Elotuzumab IV at 20mg/kg

Also known as: BMS-901608

Elo Pom Car and Dex

Pomalidomide DRUG

Pomalidomide PO at 3mg

Also known as: CC-4047, Pomalyst

Elo Pom Car and Dex

Carfilzomib DRUG

Carfilzomib 20mg/m2 IV Carfilzomib 56mg/m2 IV

Also known as: Kyprolis

Elo Pom Car and Dex

Dexamethasone DRUG

Dexamethasone 28mg PO Dexamethasone 40mg PO or IV Dexamethasone 8mg IV

Also known as: Steroid

Elo Pom Car and Dex

Eligibility Criteria

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

You may qualify if:

• ECOG/Zubrod performance status of 0-2 at study entry
• Has a diagnosis of high-risk MM by showing any of the following a-f criteria: :
• Presence of conventional cytogenetic markers such as deletion of 17p-p53, translocations involving t(14;16) and t(14;20)
• Plasma cell leukemia (PCL) (\> 2.0 × 109/L circulating plasma cells by standard differential)
• Extramedullary MM
• Doubling in levels of a MM markers in the past 3 months such as any of the following criteria alone or in combination: i) Serum M-protein ≥ 1.0 g/dL, or ii) Urine M-protein ≥ 400 mg/24 hours, or iii) Only in patients who do not meet i or ii, then use serum free light chain (SFLC) \> 200 mg/L (involved light chain) and an abnormal kappa/lambda ratio
• Refractoriness to their most recent lenalidomide-containing regimen and proteasome inhibitor-containing regimen.
• Renal failure related to MM with creatinine clearance (CrCl) \>15 mL/min but \<30 mL/min as calculated by Cockcroft-Gault equation (Appendix 14.8).
• Has previously received more than two lines of therapy including a lenalidomide-containing regimen and proteasome inhibitor-containing regimen.
• Currently demonstrating progressive disease
• Life expectancy greater than 3 months
• Laboratory test results within these ranges at Screening and confirmed at enrollment prior to drug dosing on Cycle 1 Day 1:
• ANC ≥ 1.5 x 109/L; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 1.0 x 109/L
• Platelet count ≥ 75 x 109/L; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 50 x 109/L
• Hemoglobin ≥ 8 g/dL

You may not qualify if:

• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 19
• Waldenström's macroglobulinemia
• Received the following prior therapy:
• Elotuzumab
• Chemotherapy within 3 weeks of study drugs (6 weeks for nitrosourea, melphalan or monoclonal antibodies)
• Corticosteroids (\>10 mg/daily prednisone or equivalent) within 3 weeks of study drugs
• Immunomodulatory therapy within one week before study drugs
• Antibody therapy within 3 weeks before study drugs
• Extensive radiation therapy (total maximum radiation doses of 50Gy to any individual site or 30Gy for the disseminated MM of bone) within 3 weeks before study drugs. Receipt of localized radiation therapy does not preclude enrollment.
• Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 3 weeks prior to first dose
• Use of any other experimental drug or therapy within 3 weeks of study drugs
• Received the following transplant therapies:
• Less than 12 weeks from auto transplant
• Less than 16 weeks from allo transplant
• Less than 4 weeks since any plasmapheresis

Sponsors & Collaborators

• Oncotherapeutics: lead

Study Sites (6)

California Cancer Associates for Research & Excellence (cCARE)

Encinitas, California, 92024, United States

Location

Robert A. Moss, MD, FACP, Inc

Fountain Valley, California, 92708, United States

Location

Pacific Cancer Care

Monterey, California, 93940, United States

Location

James Berenson, MD, Inc

West Hollywood, California, 90069, United States

Location

Millennium Oncology Research Clinic

Pembroke Pines, Florida, 33024, United States

Location

Regional Cancer Care Associates MD LLC

Bethesda, Maryland, 20817, United States

Location

Related Publications (1)

• Yashar D, Spektor TM, Martinez D, Ghermezi M, Swift RA, Eades B, Schwartz G, Eshaghian S, Lim S, Vescio R, Berenson JR. A phase 2 trial of the efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib and dexamethasone for high-risk relapsed/refractory multiple myeloma. Leuk Lymphoma. 2022 Apr;63(4):975-983. doi: 10.1080/10428194.2021.2005044. Epub 2021 Nov 24.

  PMID: 34818965 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

elotuzumab; pomalidomide; carfilzomib; Dexamethasone; Steroids

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• James R Berenson, MD

  Oncotherapeutics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: April 7, 2017
• Study Start: March 13, 2017
• Primary Completion: October 25, 2019
• Study Completion: January 23, 2020
• Last Updated: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)