Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma

Leukemia Clinical Trial

Official title: Phase I Study of T Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults With B Cell Malignancies

Status Completed

Clinical Trial Summary

Background:

• Although progress has been made in treating children with B-cell cancers such as leukemia or lymphoma, many children do not respond to the standard treatments. One possible treatment involves collecting white blood cells called T cells from the person with cancer and modifying the cells to attack the B-cell cancer. The cells can then be given back to the participant. This study will use T cells that have been modified to attack the cluster of differentiation 19 (CD19) protein, which is found on the surface of some B-cell cancers.

Objectives:

• To see if anti-CD19 modified white blood cells are a safe and effective treatment for children and young adults with advanced B-cell cancer.

Eligibility:

• Children and young adults between 1 and 30 years of age who have B-cell cancer (leukemia or lymphoma) that has not responded to standard treatments.

• The leukemia or the lymphoma must have the CD19 protein.

• There must be adequate organ function.

Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow biopsies may be performed depending on the type of cancer.

• Participants will undergo a process where white blood cells are collected, called apheresis. These cells will be modified to contain the anti-CD19 gene.

• Participants will have 3 days of chemotherapy to prepare their immune system to accept the modified cells.

• Participants will receive an infusion of their own modified white blood cells. They will remain in the hospital until they have recovered from the treatment.

• Participants will have frequent follow-up visits to monitor the outcome of the treatment.

• If the participant benefits from the treatment, then he/she may have the option for another round of treatment.

Clinical Trial Description

Background:

Chimeric antigen receptors (CAR) that recognize the cluster of differentiation 19(CD19) antigen have been constructed and are in clinical trials at several institutions. In this trial, the Pediatric Oncology Branch (POB) will utilize a chimeric receptor containing the signaling domains of cluster of differentiation 28 (CD28) and cluster of differentiation 3 (CD3)-zeta, currently under study in the Center for Cancer Research (CCR) in adults, for children and young adults with CD19 expressing malignancies.

In co-cultures with CD19-expressing acute lymphoblastic leukemia cells, anti-CD19-CAR-transduced T cells show robust killing, and in xenograft models, can rapidly clear CD19- expressing ALL cell lines.

Objectives:

1. Primary: To determine the safety and feasibility of administering escalating doses of anti-CD19-CAR engineered peripheral blood lymphocytes in two strata (prior allogeneic stem cell transplant [SCT] vs. no prior SCT) of children and young adults with B cell malignancies following a cyclophosphamide/fludarabine preparative regimen. COMPLETED March 2014.

2. Primary: To determine the safety of administering cells in two groups of children and young adults with B-cell malignancies expressing CD19:

• Arm 1 - Patients without high-burden disease or patients for whom chemotherapy toxicity is a concern will receive standard preparative regimen.

• Arm 2 - Patients with high-burden disease who receive standard chemotherapy to reduce burden, (defined as patients with ALL who have M3 bone marrow blasts and/or presence of peripheral blood blasts on routine complete blood count (CBC), or patients with lymphoma).

3. Primary: To determine the feasibility of administering anti-CD19 CAR transduced T cells within 21 days of the target date in children and young adults with B-cell malignancies expressing CD19 enrolled on arm 2: Patients with high-burden disease who receive standard chemotherapy to reduce burden.

1) Secondary: 1) To determine if the administration of anti-CD19-CAR engineered peripheral blood lymphocytes can mediate antitumor effects in children with B cell high-burden disease after standard chemotherapy, or in patients without high-burden disease who receive standard preparative regimen. 2) To evaluate the ability of CRS treatment algorithm to reduce the incidence of Grade 4 Cytokine Release Syndrome (CRS) to less than or equal to 10% of patients. 3) To measure persistence of adoptively-transferred anti-CD19-CAR-transduced T cells in the blood, bone marrow and cerebrospinal fluid (CSF) of patients. 4) To describe the toxicity of administration of anti-CD19-CAR engineered peripheral blood lymphocytes in children and young adults with central nervous system (CNS) disease.

Eligibility:

Patients 1-30 years of age, at least 15 kg, with a CD19-expressing B-cell malignancy that has recurred after or not responded to one or more standard chemotherapy-containing regimens for their malignancy and is deemed incurable by standard therapy. Patients with a history of allogeneic stem cell transplant who meet all eligibility criteria are eligible to participate.

Design:

• PBMC will be obtained by leukapheresis. Anti-CD19 CAR T cells will be manufactured from fresh or frozen peripheral blood mononuclear cells (PBMCs). On Day -7, PBMC will be enriched for cluster of differentiation 3 (CD3)+ cells and cultured in the presence of anti-CD3/-cluster of differentiation 28 (CD28) beads followed by retroviral vector supernatant containing the anti-cluster of differentiation 19 (CD19) CAR. Total culture time is approximately 7-14 days.

• Patients will be divided into the 2 groups listed above.

Arm 1: Patients will begin preparative regimen comprising fludarabine 25 mg/m(2) on Days -4, -3 and -2 and cyclophosphamide 900 mg/m(2) on day -2.

Arm 2: Patients with high-disease burden will be treated with intensive standard of care chemotherapy to decrease disease burden during cell manufacturing.

• All patients: The CD19-CAR cells will be infused on Day 0, with up to a 72h delay allowed for fresh cells or a 21 day delay if cells are cryopreserved, if needed for resolution of clinical toxicities or to generate adequate cell numbers.

• The previously determined maximum tolerated dose (MTD) of 1 X 10(6) will be administered intravenously.

• Patients will be monitored for toxicity, response and T cell persistence. ;

Related Conditions & MeSH terms

• ALL
• B Cell Lymphoma
• Large Cell Lymphoma
• Leukemia
• Lymphoma
• Lymphoma, B-Cell
• Non-Hodgkin Lymphoma

• NCT number: NCT01593696
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: June 29, 2012
• Completion date: October 2, 2017