Study of T Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma

NCT02215967 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 14016814-C-0168
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- T cells are white blood cells that fight several cancers. One cancer therapy involves removing a persons' T cells, changing them in a lab, and then returning them to the person. Researchers want to see if this helps people with multiple myeloma. Objective: \- To test the safety of giving anti-B-Cell Maturation Antigen T cells to people with multiple myeloma. Eligibility: \- Adults ages 18-70 with multiple myeloma that has not responded to standard therapies. Design:

• Participants may be screened with:
• Medical history
• Physical exam
• Blood and urine tests
• Heart tests
• Bone marrow sample
• Multiple scans and X-rays
• Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm.
• The cells will be changed in a laboratory.
• Participants will get 2 chemotherapy drugs over 3 days.
• Two days later, participants will check into the hospital. They will get an intravenous (IV) catheter in an arm or chest vein. They will get the T cells through the IV in 1 infusion.
• After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor.
• Participants will visit the clinic 1, 2, 3, 4, 6, and 12 months after the infusion, then every 6 months. A bone marrow sample will be taken at the 2-month visit.
• Participants blood will be collected for several years. Participants will have an annual physical at National Institutes of Health (NIH) for 5 years after the infusion. Then for 10 years they will answer health questionnaires.

Conditions

Myeloma, Plasma-Cell; Myeloma-Multiple

Keywords

Immunotherapy; Anti-BCMA-CAR; Gene Therapy; Adoptive T Cell Therapy; Plasma Cell Malignancy

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities

  Dose limiting toxicities are defined as follows: Grade 3 toxicities possibly or probably related to either the anti-BCMA CAR T cells or the fludarabine and cyclophosphamide chemotherapy and lasting more than 7 days. Grade 4 toxicities possibly or probably related to the study interventions.

  After the start of treatment and up to 60 days

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

  Date treatment consent signed to date off study, approx. 3 mos and 7 days for DL 0.3 x 10^6 CAR + T cells, 4 mos and 4 days for 1.0 x 10^6 CAR + T cells, 9 mos and 13 days for 3.0 x 10^6 CAR + T cells, and 48 mos and 12 days for 9.0 x 10^6 CAR + T cells.

Secondary Outcomes (1)

• Number of Participants With Best Response

  From start of treatment up to 84 weeks

Study Arms (1)

Multiple Myeloma

EXPERIMENTAL

Dose Escalation with 5 dose levels based on the patients actual bodyweight

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells

Interventions

Cyclophosphamide DRUG

300 mg/m\^2 intravenous (IV) over 30 minutes on days -5, -4, and -3

Also known as: Cytoxan

Multiple Myeloma

Fludarabine DRUG

30 mg/m\^2 intravenous (IV) over 30 minutes immediately following the cyclophosphamide on day -5, -4, and -3

Also known as: Fludara

Multiple Myeloma

Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells BIOLOGICAL

0.3x10\^6- 15.0x10\^6 CAR+ T cells per kg of recipient bodyweight one time dose on day 0

Multiple Myeloma

Eligibility Criteria

• Age: 18 Years - 73 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple Myeloma criteria
• Clear B-cell maturation antigen (BCMA) expression must be detected on greater than 50% of malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry. These assays must be performed at the National Institutes of Health. It is not required that the specimen used for BCMA determination comes from a sample that was obtained after the patient's most recent treatment. BCMA expression will need to be documented on the majority of malignant plasma cells at some time after the original anti-BCMA chimeric antigen receptor (CAR) T-cell infusion in all patients undergoing a second anti-BCMA CAR T-cell infusion. If paraffin embedded unstained samples of bone marrow involved with multiple myeloma (MM) or a plasmacytoma are available, these can be shipped to the National Institutes of Health (NIH) for BCMA staining, otherwise new biopsies will need to be performed for determination of BCMA expression.
• Bone marrow plasma cells must make up 30% or less of total bone marrow cells based on a bone marrow biopsy performed within 30 days of the start of protocol treatment.
• Patients must have received at least 3 different prior treatment regimens for multiple myeloma
• Patients must have measurable MM as defined by at least one of the criteria below.
• a. One or more of these abnormalities defines measurable disease:
• Serum M-protein greater or equal to 1 g/dl (10 g/l).
• Urine M-protein greater or equal to 200 mg/24 h.
• Serum free light chain (FLC) assay: involved FLC level greater or equal to10 mg/dl (100 mg/l) provided serum FLC ratio is abnormal.
• A biopsy-proven plasmacytoma
• Patients must have multiple myeloma that meets the criteria for one of the following Disease categories: (1) progressive disease or (2) relapse from Complete Remission (CR) as described in the International Uniform Response Criteria for Multiple Myeloma and as listed below.
• Progressive Disease (which requires 1 or more of the following)(A):
• Increase of greater than or equal to 25% from the lowest response value (nadir) in any one or more of these parameters:
• Serum M-component (the absolute increase must be greater than or equal to 0.5 g/dL) (B) and/or
• Urine M-component and/or (the absolute increase must be greater than or equal to 200 mg/24 h)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol. 2013 May;10(5):267-76. doi: 10.1038/nrclinonc.2013.46. Epub 2013 Apr 2.

  PMID: 23546520 BACKGROUND

• Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, Gress RE, Hakim FT, Kochenderfer JN. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013 Apr 15;19(8):2048-60. doi: 10.1158/1078-0432.CCR-12-2422. Epub 2013 Jan 23.

  PMID: 23344265 BACKGROUND

• Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, Yang JC, Kammula US, Devillier L, Carpenter R, Nathan DA, Morgan RA, Laurencot C, Rosenberg SA. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012 Mar 22;119(12):2709-20. doi: 10.1182/blood-2011-10-384388. Epub 2011 Dec 8.

  PMID: 22160384 BACKGROUND

• Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, Stetler-Stevenson M, Salem D, Yuan C, Pavletic S, Kanakry JA, Ali SA, Mikkilineni L, Feldman SA, Stroncek DF, Hansen BG, Lawrence J, Patel R, Hakim F, Gress RE, Kochenderfer JN. T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. J Clin Oncol. 2018 Aug 1;36(22):2267-2280. doi: 10.1200/JCO.2018.77.8084. Epub 2018 May 29.

  PMID: 29812997 DERIVED

• Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, Brudno JN, Stetler-Stevenson M, Feldman SA, Hansen BG, Fellowes VS, Hakim FT, Gress RE, Kochenderfer JN. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016 Sep 29;128(13):1688-700. doi: 10.1182/blood-2016-04-711903. Epub 2016 Jul 13.

  PMID: 27412889 DERIVED

• Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7(11):1187-99. doi: 10.2217/imt.15.77. Epub 2015 Sep 15.

  PMID: 26370838 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; bis(3-bis(4-chlorophenyl)methyl-4-dimethylaminophenyl)amine; Receptors, Chimeric Antigen; Automobiles

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Receptors, Artificial; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Antigen, T-Cell; Receptors, Antigen; Receptors, Immunologic; Receptors, Cytoplasmic and Nuclear; Motor Vehicles; Transportation; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Dr. James N. Kochenderfer
• Organization: National Cancer Institute

kochendj@mail.nih.gov

240-760-6062

Study Officials

• James N Kochenderfer, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 12, 2014
• First Posted: August 13, 2014
• Study Start: August 12, 2014
• Primary Completion: April 25, 2019
• Study Completion: August 15, 2019
• Last Updated: October 8, 2019
• Results First Posted: October 8, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)