Safety Study of Anti LewisY Chimeric Antigen Receptor in Myeloma, Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT01716364 | Unknown Phase 1 DMC

• 1 other identifier: LeYPh1
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with some forms of acute myeloid leukemia (AML) and multiple myeloma (MM) are not cured with conventional therapy and new approaches are needed. For the last 15 years we have investigated the potential of using a patient's own T cells (a type of white blood cell \[WBC\]) to eradicate the tumor. We have demonstrated the feasibility of this approach in cell culture and animal models of AML and MM. Over the last 5 years we have been preparing to treat patients as part of a Phase I (first in human) clinical trial. The trial treatment involves collecting the patient's own WBCs from the blood by a standard well established and safe process called apheresis. The cells are then cultured in a specialized laboratory (under Good Manufacturing Practice conditions, similar to standards under which pharmaceuticals are produced) over 12 days to convert the cells to specialized tumor-attacking T cells. Early in that culture process the cells are exposed to a virus (that is modified so that it cannot infect or replicate outside the special culture conditions) that contains a special gene. Via the virus, this gene inserts into the patient's T cells in culture and gets incorporated into the T cell's genetic machinery. As the T cells replicate, the new gene produces a protein receptor that becomes part of the patient's T cells. This protein receptor on the T cells has the capacity to specifically recognize and bind to a protein on the leukemia or myeloma cells called the "Lewis Y" antigen. After the modified T cells are infused into the patient, they home into the bone marrow (this tracking is monitored by special radiological techniques) where the new protein receptor on the T cell surface can recognize and bind to the cancer cells (which express Lewis Y). Once bound onto the cancer cells, the T cells get activated and subsequently replicate and kill the cancer cells. The novelty of this approach is that the T-cells will only kill cells that have the Lewis Y on their surface - the cancer cells. Moreover, because there are few normal cells in a person's body that carry Lewis Y, this treatment is likely to only have minor side effects. This gene therapy trial is unique and although the primary purpose is to test the safety of this approach, patients will be monitored closely for anti-tumor responses. As the trial progresses, the dose of T cells infused will increase, in the hope that this will result in a better and stronger immune response to the leukemia or myeloma.

Conditions

Multiple Myeloma; Acute Myeloid Leukaemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events.

  Up to 3 years

Secondary Outcomes (14)

• Percentage of infused labelled cells localizing in bone marrow

  Up to 3 years

• Percentage of infused labelled cells localizing in soft tissue or plasmacytoma.

  Up to 3 years

• Presence or absence of anti-LeY positive T-cells in peripheral blood and bone marrow.

  Up to 3 years

• Percentage of anti LeY positive T-cells in peripheral blood and bone marrow.

  Up to 3 years

• Serum IFN-γ and IL-2 levels.

  Up to 3 years

Study Arms (1)

Anti-LeY- scFv-CD28-ζ vector.

EXPERIMENTAL

Anti-LeY- scFv-CD28-ζ vector, a non-pathogenic, replication-incompetent retroviral vector specifically designed for this study and produced by EUFETS under GMP-conditions.

Biological: Anti-LeY- scFv-CD28-ζ vector,.

Interventions

Anti-LeY- scFv-CD28-ζ vector,. BIOLOGICAL

Anti-LeY- scFv-CD28-ζ vector.

Eligibility Criteria

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

You may qualify if:

• Applicable to all Patients
• Patient is able to undergo apheresis of peripheral blood mononuclear cells (PBMC) within eight weeks following registration.
• White cell count (WCC) \<30/nL as higher WCC could interfere with the apheresis of PBMC.
• Patient has an ECOG performance status of 0 - 1.
• Patient is deemed capable of undergoing the planned study procedures
• Patient has adequate organ function:
• bilirubin \<1.5x upper limit of normal (ULN), AST/ALT ≤2.5 x ULN except in patients with Gilbert's syndrome
• Serum Creatinine \< 1.5 ×ULN or creatinine clearance \> 50ml/min
• Amylase, lipase ≤1.5xULN
• Lymphocyte count of ≥0.5x109/L
• \> 18 years of age.
• Patient has provided written informed consent.
• No chemotherapy or treatment with G-CSF within 4 weeks prior to the planned apheresis.
• Applicable to patients with multiple myeloma
• Patient has histologically or cytologically confirmed diagnosis of multiple myeloma plus one or more of the criteria set out below must apply:

You may not qualify if:

• None of the following should apply:
• Patient has had immunotherapy including corticosteroids (except Prednisolone \<10mg or equivalent) within the last 4 weeks or is planned to receive such therapy prior to apheresis of PBMC.
• Patient has been given chemotherapy and/or G-CSF in the last 4 weeks.
• Patient has been planned to receive chemotherapy and/or growth factors of any type before planned apheresis of PBMC
• Patient has been given experimental therapy within the last 4 weeks or is planned to receive experimental therapy prior to apheresis of PBMC
• Patient has known clinically significant autoimmune disease with positive serology for RHF (\>20kU/L) or ANA (titre \>1:40)
• Patient has a history of idiopathic pancreatitis Patient has known, biopsy proven autoimmune inflammatory disease of the gastrointestinal tract
• Women of child bearing potential (WOCBP) who are unwilling or unable to use an effective method of contraception to avoid pregnancy for the entire study period and for at least 3 months after completion of study treatment.
• Women who are pregnant or breastfeeding.
• Men who are unwilling or unable to use an acceptable method of contraception for the entire study period and for at least 3 months after completion of study treatment if their sexual partners are WOCBP.
• Patient has known central nervous system (CNS) disease.
• Patient has a serious uncontrolled medical disorder which would impair the ability to receive protocol therapy.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

Location

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

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; Leukemia, Myeloid; Leukemia; Bone Marrow Diseases

Study Officials

• Miles Prince, MD

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: October 29, 2012
• Study Start: January 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 4, 2012

Record last verified: 2012-10

Locations

AU (1)