A Study of Venetoclax in Combination With Isatuximab and Dexamethasone for Relapsed/Refractory Multiple Myeloma

NCT06115135 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BCC-VID-2022
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

A phase 2 study of venetoclax in combination with isatuximab and dexamethasone for relapsed/refractory multiple myeloma patients with t(11;14)

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma, Refractory

Keywords

Multiple Myeloma; MM; RRMM; Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events [Safety]

  Safety will be measured by counting the occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 criteria

  [Time Frame: 54 months]

• Overall response rate (ORR) as a measure of efficacy

  To assess the overall response rate (ORR = CR + VGPR + PR)

  [Time Frame: 54 months]

• Clinical benefit rate (CBR) as a measure of efficacy

  (CBR = CR + VGPR + PR + MR)

  [Time Frame: 54 months]

Secondary Outcomes (5)

• Assessment of the time to progression as a measure of efficacy (TTP)

  [Time Frame: 54 months]

• Progression Free Survival (PFS)

  [Time Frame: 54 months]

• Time to first response (TTFR)

  [Time Frame: 54 months]

• Duration of response (DOR)

  [Time Frame: 54 months]

• Overall survival (OS)

  [Time Frame: 54 months]

Other Outcomes (1)

• Biomarker (sBCMA) screening for all patients

  [Time Frame: 54 months]

Study Arms (1)

open-label

EXPERIMENTAL

This is a Phase 2, multicenter, open-label study evaluating the safety and efficacy of venetoclax in combination with isatuximab and dexamethasone among RRMM patients who show the t(11;14) marker and currently show PD and have received at least 3 prior lines of therapy for multiple myeloma. All subjects in Dose Level 0 will receive 1) venetoclax, PO, at 400 mg every day (QD) on Days 1-28 of a 28-day cycle, 2) dexamethasone 40 mg IV, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle where day 8 and 22 doses may be administered PO; and 3) isatuximab 10mg/kg, IV, on Days 1, 8, 15, and 22 of the first 28-day cycle, and then Days 1 and 15 during subsequent 28-day cycles. The primary safety analysis will focus on determining the DLTs for the study regimen, and occurrence of AEs throughout the study.

Drug: Venetoclax

Interventions

Venetoclax DRUG

All subjects in Dose Level 0 will receive 1) venetoclax, PO, at 400 mg every day (QD) on Days 1-28 of a 28-day cycle, 2) dexamethasone 40 mg IV, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle; and 3) isatuximab 10mg/kg, IV, on Days 1, 8, 15, and 22 of the first 28-day cycle, and then Days 1 and 15 during subsequent 28-day cycles.

Also known as: VENCLEXTA

open-label

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a diagnosis of MM based on standard criteria as follows: Myeloma Criteria: Must be At least 1 of 2
• Clonal bone marrow plasma cells \>10%
• Biopsy-proven bony or extramedullary plasmacytoma
• Active Myeloma criteria: Must Meet At Least ONE of the Following:
• Meet at least one of the sub-criteria for #1 Evidence of End Organ Damage (a, b, c, or d), OR Meet sub-criteria #2. 60% or greater bone marrow plasma cells, OR Meet sub-criteria #3 Serum free light chain ratio, OR Meet sub-criteria #4 More than one focal lesion on MRI \> 5mm in size.
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically
• Hypercalcemia: serum calcium \>0.25 mmol/L (\>1mg/dL) higher than the upper limit of normal or \>2.75 mmol/L (\>11mg/dL)
• Renal insufficiency: creatinine clearance \<40 mL per minute or serum creatinine \>177mol/L (\>2mg/dL)
• Anemia: hemoglobin value of \>20g/L below the lowest limit of normal, or a hemoglobin value \<100g/L
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET/CT. If bone marrow has \<10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement
• % or greater clonal plasma cells on bone marrow examination
• Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg/L (a patient's involved free light chain either kappa or lambda is the one that is above the normal reference range; the uninvolved free light chain is the one that is typically in, or below, the normal range)
• More than one focal lesion on MRI that is at least 5mm or greater in size The patient must have met the criteria for Active Myeloma at some stage following the diagnosis of Myeloma. Source documentation for both Myeloma and Active Myeloma will be required.
• \. Currently has MM with measurable disease, defined as:
• a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or urine monoclonal protein levels of at least 200 mg/24 hours

You may not qualify if:

• Participant has a history of intolerability to any of the study drugs
• Participant has any of the following conditions: amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known human immunodeficiency viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of screening, or congestive heart failure New York Heart Association (NYHA) Class greater than or equal to 3, Major surgery within 4 weeks prior to screening, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to screening, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to screening, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study
• Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study
• If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD)
• Participants that are pregnant or breast feeding
• Participants with hypersensitivity to any study medications and/or their excipients
• Treatment with an anti-CD38 antibody (daratumumab or isatuximab) within the last 3 weeks
• For those patients treated with an anti-CD38 antibody (daratumumab or isatuximab), alone or in combination, without achieving a best response of at least MR
• Treatment with venetoclax
• Treatment with any of the following prior to the first dose of study drug:
• Chemotherapy within 3 weeks of starting study drugs
• Corticosteroids (\>20 mg per day prednisone or equivalent) within 3 weeks of starting study drugs
• Immunotherapy, antibody therapy, immunomodulatory agents, or proteasome inhibitors within 3 weeks of starting study drugs
• Extensive radiation therapy within 28 days of starting study drugs. Receipt of localized radiation therapy does not preclude enrollment
• Use of any other experimental drug or therapy within 28 days of starting study drugs

Sponsors & Collaborators

• Oncotherapeutics: lead

Study Sites (2)

Berenson Cancer Center

West Hollywood, California, 90069, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Related Publications (9)

• Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129. Epub 2007 Nov 1.

  PMID: 17975015 BACKGROUND

• Bahlis NJ, Baz R, Harrison SJ, Quach H, Ho SJ, Vangsted AJ, Plesner T, Moreau P, Gibbs SD, Coppola S, Yang X, Al Masud A, Ross JA, Bueno O, Kaufman JL. Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14). J Clin Oncol. 2021 Nov 10;39(32):3602-3612. doi: 10.1200/JCO.21.00443. Epub 2021 Aug 13.

  PMID: 34388020 BACKGROUND

• Touzeau C, Le Gouill S, Mahe B, Boudreault JS, Gastinne T, Blin N, Caillon H, Dousset C, Amiot M, Moreau P. Deep and sustained response after venetoclax therapy in a patient with very advanced refractory myeloma with translocation t(11;14). Haematologica. 2017 Mar;102(3):e112-e114. doi: 10.3324/haematol.2016.160408. Epub 2017 Jan 5. No abstract available.

  PMID: 28057737 BACKGROUND

• Martin T, Baz R, Benson DM, Lendvai N, Wolf J, Munster P, Lesokhin AM, Wack C, Charpentier E, Campana F, Vij R. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Jun 22;129(25):3294-3303. doi: 10.1182/blood-2016-09-740787. Epub 2017 May 8.

  PMID: 28483761 BACKGROUND

• Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Mace S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. doi: 10.1016/S0140-6736(19)32556-5. Epub 2019 Nov 14.

  PMID: 31735560 BACKGROUND

• Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Spicka I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Mace S, Martin T; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021 Jun 19;397(10292):2361-2371. doi: 10.1016/S0140-6736(21)00592-4. Epub 2021 Jun 4.

  PMID: 34097854 BACKGROUND

• Rahbari KJ, Nosrati JD, Spektor TM, Berenson JR. Venetoclax in Combination With Bortezomib, Dexamethasone, and Daratumumab for Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):e339-e343. doi: 10.1016/j.clml.2018.06.003. Epub 2018 Jun 18. No abstract available.

  PMID: 30033209 BACKGROUND

• Regidor B, Goldwater MS, Wang J, Bujarski S, Swift R, Eades B, Emamy-Sadr M, Eshagian S, Schwartz G, Spektor TM, Berenson JR. Low dose venetoclax in combination with bortezomib, daratumumab, and dexamethasone for the treatment of relapsed/refractory multiple myeloma patients-a single-center retrospective study. Ann Hematol. 2021 Aug;100(8):2061-2070. doi: 10.1007/s00277-021-04555-3. Epub 2021 May 14.

  PMID: 33987683 BACKGROUND

• Smith ML, Newland AC. Treatment of myeloma. QJM. 1999 Jan;92(1):11-4. doi: 10.1093/qjmed/92.1.11.

  PMID: 10209667 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

venetoclax

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

Study Officials

• James Berenson, MD

  Oncotherapeutics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Bailey

CONTACT

(310) 464-2190; rbailey@oncotherapeutics.com

Yohana Sebhat

CONTACT

310-810-3158; ysebhat@oncotherapeutics.com

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: August 11, 2023
• First Posted: November 2, 2023
• Study Start: June 20, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)