Isatuximab During Stem Cell Collection and Transplant in Patients With Multiple Myeloma and Lymphoma

Randomized Phase 2 Trial of Isatuximab During Autologous Stem Cell Collection and Transplantation Period in Patients With Multiple Myeloma, Relapsed Hodgkin's and Non-Hodgkin's Lymphoma

The purpose of this study is to see if Isatuximab can alter the immune system in patients with multiple myeloma or lymphoma upon recovery from the autologous stem cell transplantation. The investigators will see if Isatuximab makes changes to the immune system so that upon recovery from the transplant, the immune system can fight the cancer. This study will have two arms. On one arm (control arm), participants will receive standard transplant procedures and on the other arm (experimental arm), participants will receive Isatuximab in addition to the standard transplant procedures. The assignment to these arms is done randomly (determined by chance, like flipping a coin) by a computer. Each participant will have about 66% chance of getting on the experimental arm and about 33% chance of getting on the control arm.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Multiple Myeloma; Non-Hodgkin Lymphoma; Relapsed Hodgkin's Disease, Adult
• Intervention / Treatment: Drug: Isatuximab; Other: Standard Procedures

Detailed Description

Relapse post-autologous stem cell transplantation (ASCT) remains a major challenge in the treatment of multiple myeloma (MM) and Lymphoma. The immune reconstitution post-ASCT has a major impact on the outcomes of ASCT, however effective methods to improve upon immune reconstitution have not been developed and the use of novel immunomodulators remains relatively unexplored. In addition, numerous studies have demonstrated the profound impact of graft composition on transplant outcomes, but not a single prospective study has addressed this issue successfully. In this study, the investigators intend to test a novel double pronged method of changing the immune repertoire post ASCT by modifying graft composition and improving effector T cell recovery and function post ASCT. In this study, the investigators intend to generate new information on immune modulation post-ASCT. In addition, the CD38 antibodies have not been evaluated as therapy for B-cell non-Hodgkin Lymphoma (NHL). If this study shows significant immunomodulator activity of this approach, cluster of differentiation 38 (CD38) antibodies could be further evaluated in combination with ASCT in NHL.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Research Nurse Navigator; Phone Number: 212-342-5162; Email: cancerclinicaltrials@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Principal Investigator: Divaya Bhutani, MD
      • Contact: Research Nurse Navigator; Phone Number: 212-342-5162; Email: cancerclinicaltrials@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Following diagnoses are eligible for inclusion in the study:

   A) Multiple Myeloma with ASCT used as consolidation after first line induction therapy or at first relapse.

   B) Relapsed/Refractory Hodgkin's disease

   C) Non-Hodgkin's Lymphomas as follows

   • Relapsed/Refractory Diffuse large B cell lymphoma
   • Relapsed/Refractory indolent or relapsed/refractory transformed indolent B cell lymphomas as consolidation after second line therapy
   • Mantle Cell lymphoma as consolidation after first-line therapy
   • Peripheral T cell lymphoma as consolidation after first-line therapy or at relapse or primary refractory disease
2. Patients undergoing first ASCT will be eligible for the study.
3. Any prior therapy for the malignancy except CD38 antibody within the last 12 months is allowed.
4. Age ≥18 years
5. Life expectancy of greater than 6 months.

Exclusion Criteria:

1. Previously exposure to a CD38 antibody during the last 12 months.
2. Participants who are receiving any other investigational agents concurrently or received any investigational agent within the last 8 weeks.
3. History of severe allergic reactions or anaphylaxis attributed to compounds of similar chemical or biologic composition to Isatuximab.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
5. Pregnant and Lactating women
6. HIV-positive status due to increased risk of infection when treated with immunosuppressive therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isatuximab and Standard Procedures; Subjects will receive the study drug Isatuximab in addition to standard procedures for transplant	Drug: Isatuximab; Isatuximab in IV form 10 mg/kg doses; Other Names: Sarclisa
Experimental: Standard procedures; Subjects will receive standard procedures for transplant.	Other: Standard Procedures; Standard procedures (standard of care) for transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the total lymphocyte count	Change in total lymphocyte count measured from blood sample	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	The number of adverse events recorded for participants using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Up to 1 year
Percentage of participants with absolute lymphocyte count >500 cells/microliter	Percentage of participants with an absolute lymphocyte count of >500 cells/microliter on Day 30 post transplant	Day 30
CD8 and CD4 Subsets	Immune cell phenotyping ( cluster of differentiation 8 (CD8) and cluster of differentiation 4 (CD4) subsets) in the peripheral blood using flow cytometry based analysis	Up to 1 year
Percentage of activated B and T regulatory cells	Percentage of activated B and T regulatory cells in the peripheral blood	Up to 1 year
Percentage of activated helper and effector T cells	Percentage of activated helper and effector T cells in the peripheral blood	Up to 1 year
Percentage of Natural Killer (NK) cells	Percentage of NK cells in the peripheral blood	Up to 1 year

Collaborators and Investigators

• Sponsor: Divaya Bhutani
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Divaya Bhutani, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Stem cell transplant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: AAAT7444

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No