Phase II Study of Salvage Radiation Treatment After B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy for Relapsed Refractory Multiple Myeloma

This study is a Phase II study to determine the preliminary safety and efficacy of salvage radiation treatment after BCMA CAR-T therapy in subjects with RRMM.

The study population will consist of subjects with RRMM previously treated with SOC BCMA CAR-T cell therapy with active disease on the D30+ PET or other imaging scan after CAR-T infusion. Patients who are planned for salvage chemotherapy less than 14 days after completion of radiation treatment will be excluded.

Radiation treatment will be to bony or soft tissue plasmacytomas in up to five radiation treatment fields to 10-20Gy (or equivalent dose in 2Gy fractions of 10-21Gy). Final dose, target, and technique are per treating radiation physician discretion within these guidelines.

Thirty patients will be enrolled. The co-primary endpoints are objective response rate (ORR) at 6 months and duration of response (DOR) among responders.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Plasma Cell Neoplasm; Malignant Plasma Cell Neoplasm
• Intervention / Treatment: Drug: Radiation Therapy

Detailed Description

Objectives

Primary Objective:

• The primary objective of the study is to evaluate the preliminary efficacy of salvage radiation therapy after BCMA CAR-T cell therapy in subjects with RRMM.

Secondary Objectives:

• Evaluate the safety of and other efficacy parameters of radiation treatment after BCMA CAR-T cell therapy in subjects with RRMM

Exploratory Objectives:

• Evaluate the immunophenotype and/or expression profile, and perform functional bulk and single cell analysis of CAR T cells, endogenous T cells as well as other immune cells in the blood, bone marrow and/or tumor tissue with BCMA CAR-T therapy and RT
• Evaluate changes in the levels of cytokines, chemokines, and soluble factors in the blood with BCMA CAR-T therapy and RT
• Evaluate changes in T cell receptor repertoire with BCMA CAR-T therapy and RT
• Evaluate gut microbiome of patients treated with BCMA CAR-T therapy and RT

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Penny Fang, MD; Phone Number: (832) 260-1389; Email: pfang@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Penny Fang, MD; Phone Number: 832-260-1389; Email: pfang@mdanderson.org
      • Principal Investigator: Penny Fang, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
2. Subject is diagnosed with multiple myeloma
3. Subject previously received treatment with standard of care BCMA CAR-T cell therapy
4. Day 30 or later PET scan or other imaging scan after CAR-T infusion shows active disease
5. Subject has at least one myeloma lesion (plasmacytoma either in bone or soft tissue) that can be treated with radiation
6. Able to provide informed consent

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subjects in whom salvage chemotherapy is planned less than 14 days after the completion of radiation treatment
2. Subject is undergoing active treatment for another malignancy other than multiple myeloma
3. Pregnant women will be excluded from this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation Therapy; Radiation treatment will be to bony or soft tissue plasmacytomas in up to five radiation treatment fields to 10-20Gy (or equivalent dose in 2Gy fractions of 10-21Gy	Drug: Radiation Therapy; Given by Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma (Kumar, 2016)	through study completion, an average of 1 year
Duration of response (DoR) among responders	Time from first documentation of response (PR or greater) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Penny Fang, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2022
• Primary Completion (Estimated): December 7, 2024
• Study Completion (Estimated): December 7, 2024

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
• Other Study ID Numbers: 2021-1139; NCI-2022-03304 (Other Identifier: NCI-CTRP Clinical Trials Reporting Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No