Treated T Cells Followed by a Stem Cell Transplant in Treating Patients With Multiple Myeloma

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

Induction of Anti-Myeloma Stem Cell Immunity With Infusions of Autologous Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) (Phase I).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00938626
• Other study ID #: CDR0000646891
• Secondary ID: P30CA022453WSU-2
• Status: Completed
• Phase: Phase 1
• First received: July 11, 2009
• Last updated: September 20, 2013
• Start date: October 2009
• Est. completion date: March 2013

Study information

• Verified date: September 2013
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Giving chemotherapy followed by treated T cells before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or by killing them. After treatment, stem cells are collected from the patient's blood and stored. High-dose chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This phase I trial is studying the side effects and best way to give treated T cells followed by stem cell transplant in treating patients with multiple myeloma.

Description:

OBJECTIVES:

Primary

• To test the feasibility and safety of infusing anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells (CD20Bi-AATC) before stem cell mobilization and collection for autologous peripheral blood stem cell transplantation (PBSCT) in patients with multiple myeloma.

Secondary

• To explore functional changes in immune cell populations as a consequence of immunotherapy to test the hypothesis that CD20Bi-AATC can induce anti-clonogenic myeloma precursor cell (CMPC) effect as measured by cytotoxicity; serum cytokine levels; and serum antibody titers to myeloma cells pre-immunotherapy, after immunotherapy, and after high-dose chemotherapy and autologous PBSCT.

• To explore whether the infusion of CD20Bi-AATC reduces the proportion of plasma cells with the CD20+ CMPC phenotype in patients' bone marrow as assessed by multi-color flow cytometry before and after immunotherapy.

• To assess the proportion of bone marrow colony-forming assays before induction or salvage chemotherapy, pre-immunotherapy, and post-immunotherapy to determine whether the infusion grossly affects the bone marrow progenitor populations.

• To explore whether infusions of CD20Bi-AATC induce a B-cell defect causing an immunoglobulin deficiency after autologous PBSCT.

• To measure immunoglobulin deficiency after autologous PBSCT (e.g., quantitative IgG, IgM, and IgA levels and number of circulating T- and B-cell subsets).

OUTLINE: After completion of induction or salvage chemotherapy, patients receive immunotherapy comprising anti-CD3 x anti-CD20-armed ATC IV weekly for 2 weeks. At least 1-3 weeks after the second infusion, patients receive high-dose chemotherapy and then undergo autologous peripheral blood stem cell transplantation. Patients then undergo leukapheresis for G-CSF-mobilized autologous T-cells.

Blood samples are collected periodically to evaluate antibody titers to recall antigens; serum IgG, IgM, and IgA levels; the proportion of circulating B-cells by phenotyping for CD19, CD20, CD22, CD23, CD4, CD8, and CD38; the ability of peripheral blood mononuclear cells to kill multiple myeloma cell lines or the patient's own cryopreserved myeloma cells via cytotoxicity assays and ELISPOT assays; and human anti-mouse antibody responses to murine IgG2a (OKT3). Bone marrow biopsies are also collected to analyze the phenotype of cells (CD20+, CD138-, CD27+, CD22, etc.) via flow cytometry and the proportion of plasma cells via flow cytometry and hematoxylin-and-eosin staining.

After completion of study treatment, patients are followed up for up to 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2013
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma

• Candidate for high-dose chemotherapy and autologous stem cell transplantation

• No definite morphologic evidence of myelodysplasia on pretreatment bone marrow

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 or Karnofsky PS 70-100%

• ANC > 500/mm^3

• Platelet count = 75,000/mm^3

• Total bilirubin = 2.0 mg/dL

• AST and ALT = 3 times upper limit of normal

• Creatinine = 2.0 mg/dL

• LVEF = 45%

• Corrected pulmonary diffusion capacity = 50%

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled infections or other severe medical problems such as adrenal dysfunction

• No other active malignancy (except for nonmelanoma skin cancer) that requires myelosuppressive chemotherapy or radiotherapy

• No HIV infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• On-chemotherapy induction with thalidomide or lenalidomide with dexamethasone is allowed

• No prior stem cell transplantation

• No more than 2 prior treatment regimens (including the one during which patients undergo leukapheresis for T-cells)

• No more than 4 courses of lenalidomide in combination with other agents or as a single agent over a 1-year period

• No other concurrent immunotherapy, radiotherapy, chemotherapy, or anti-myeloma therapy at the time of the anti-CD3 x anti-CD20-armed ATC infusion

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Biological:
• anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells
After completion of induction or salvage chemotherapy, patients receive immunotherapy comprising anti-CD3 x anti-CD20-armed ATC IV weekly for 2 weeks.

Procedure:
• autologous hematopoietic stem cell transplantation
At least 1-3 weeks after the second infusion, patients receive high-dose chemotherapy and then undergo autologous peripheral blood stem cell transplantation. Patients then undergo leukapheresis for G-CSF-mobilized autologous T-cells.
• peripheral blood stem cell transplantation
At least 1-3 weeks after the second infusion, patients receive high-dose chemotherapy and then undergo autologous peripheral blood stem cell transplantation.

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cell-based toxicities according to NCI CTCAE v3.0 criteria		Up to week 4 after chemotherapy	Yes
Primary	Ability to mobilize the number of stem cells required for autologous peripheral blood stem cell transplantation (PBSCT)		By day 30 after autologous stem cell transplant (ASCT)	Yes
Secondary	Engraftment of neutrophils		At day 28 after autologous PBSCT	Yes
Secondary	Functional changes in immune cell populations		Prior to immunotherapy (IT), after IT, high dose chemotherapy (HDC)/ autologous stem cell transplant (ASCT) and boost infusion	No
Secondary	Assess proportion of erythroid blast-forming unit (BFU)-E, colony forming unit-granulocyte-macrophage (CFU)-GM, CFU-GEMM (granulocyte, erythrocyte, monocyte, megakaryocyte) & erythroid colony forming (CFU-E)	To determine whether infusions of CD20 Bi-AATC grossly affected the bone marrow progenitor populations.	Prior to induction or salvage chemotherapy; Pre & post IT	No