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

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ClinicalTrials.gov Identifier: NCT02215967
Recruitment Status : Active, not recruiting
First Posted : August 13, 2014
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

- T cells are white blood cells that fight several cancers. One cancer therapy involves removing a person s 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 NIH for 5 years after the infusion. Then for 10 years they will answer health questionnaires.

Condition or disease Intervention/treatment Phase
Myeloma, Plasma-Cell Myeloma-Multiple Drug: Cyclophosphamide Drug: Fludarabine Biological: Anti-BCMA CAR T cells Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial of T-Cells Targeting B-Cell Maturation Antigen for Previously Treated Multiple Myeloma
Study Start Date : August 12, 2014
Estimated Primary Completion Date : October 31, 2018
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: 1
Dose Escalation with 5 dose levels based on the patients actual bodyweight
Drug: Cyclophosphamide
300 mg/m2 IV over 30 minutes on days -5, -4, and -3

Drug: Fludarabine
30 mg/m2 IV over 30 minutes immediately following the cyclophosphamide on day -5, -4, and -3

Biological: Anti-BCMA CAR T cells
0.3x106- 15.0x106 CAR+ T cells per kg of recipient bodyweight one time dose on day 0




Primary Outcome Measures :
  1. Determine the safety of administering T cells expressing an BCMA CAR [ Time Frame: 2 weeks-12 months after initial dose ]
    List of adverse event frequency



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 73 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

2.1.1.1 Multiple Myeloma criteria

  • Clear 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 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 MM or a plasmacytoma are available, these can be shipped to the 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 CR as described in the International Uniform Response Criteria for Multiple Myeloma and as listed below.

    1. 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 moreof these parameters:

      1. Serum M-component (the absolute increase must be greater than or equal to 0.5 g/dL) (B) and/or
      2. Urine M-component and/or (the absolute increase must be greater than or equal to 200 mg/24 h)
      3. Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL.
      4. Bone marrow plasma cell percentage; the absolute percentage must be greater than or equal to 10%
  • Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas (defined as 50% or greater increase in the sum of the products of the cross-diameters of target lesions)
  • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder

    2. Relapse from complete remission (A)

  • Defined as one or more of the following; must be attributable to myeloma:

    1. Reappearance of serum or urine M-protein by immunofixation or electrophoresis
    2. Development of greater than or equal to 5% plasma cells in the bone marrow
    3. Appearance of any other sign of progression (i.e., new plasmacytoma, lytic bone lesion, or hypercalcemia)

(A)All relapse and progression categories require two consecutive assessments made at any time before classification as relapse or disease progression and/or the institution of any new therapy.

(B)For progressive disease, serum M-component increases of greater than or equal to 1 gm/dL are sufficient to define progression if starting M-component is greater than or equla to 5 g/dL.

2.1.1.2 Other inclusion criteria:

  • Greater than or equal to 18 years of age and less than or equal to age 73.
  • Able to understand and sign the Informed Consent Document.
  • Clinical performance status of ECOG 0-2
  • Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
  • Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests, and if confirmatory tests are negative, the patient can be enrolled.
  • Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Absolute neutrophil count greater than or equal to 1000/mm3 without the support of filgrastim or other growth factors.
  • Platelet count greater than or equal to 45,000/mm3 without transfusion support
  • Hemoglobin greater than 8.0 g/dl.
  • Less than 5% plasma cells in the peripheral blood leukocytes
  • Serum ALT and AST less or equal to 2.5 times the upper limit of the institutional normal.
  • Serum creatinine less than or equal to 1.3 mg/dL.
  • Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  • At least 14 days must have elapsed since any prior systemic therapy at the time the patient starts the cyclophosphamide and fludarabine conditioning regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
  • Because this protocol requires collection of autologous blood cells by leukapheresis in order to prepare anti-BCMA-CAR T cells, systemic anti-myeloma therapy including systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to the required leukapheresis.
  • Normal cardiac ejection fraction (greater than or equal to 50% by echocardiography) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 6 weeks of the start of the treatment protocol.
  • Patients should not take corticosteroids including prednisone, dexamethasone or any other corticosteroid for any purpose at doses higher than 5 mg/day of prednisone or equivalent dose of another corticosteroid 2 weeks before apheresis and within 2 weeks prior to CAR T-cell infusion, and at any time after the CAR T cell infusion.

2.1.2 EXCLUSION CRITTERIA:

  • Patients on any anticoagulants except aspirin are not eligible.
  • Patients that require urgent therapy due to tumor mass effects or spinal cord compression.
  • Patients that have active hemolytic anemia.
  • Patients with second malignancies in addition to multiple myeloma are not eligible if the second malignancy has required treatment within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • Active systemic infections (defined as infections causing fevers or requiring antimicrobial treatment), active coagulation disorders or other major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, history of myocardial infarction, active cardiac arrhythmias, active obstructive or restrictive pulmonary disease.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  • Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to either the required leukapheresis or the initiation of the conditioning chemotherapy regimen.
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  • History of allogeneic stem cell transplantation
  • Patients with CNS metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression).
  • Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02215967


Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: James N Kochenderfer, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02215967     History of Changes
Other Study ID Numbers: 140168
14-C-0168
First Posted: August 13, 2014    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: January 23, 2018

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Immunotherapy
Anti-BCMA-CAR
Gene Therapy
Adoptive T Cell Therapy
Plasma Cell Malignancy

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists