MB-CART19.1 in Patients With R/R ALL

NCT03321123 | Unknown Phase 2

• 1 other identifier: SCMC CART 20170920
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

Precursor-B acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. Despite major advances in ALL therapy, 20% of children and 40-50% of adults fail state-of-the art first-line treatment. But there is a strong need for alternative treatments to cure chemotherapy-refractory and relapsed B cell malignancies in pediatric patients. Relapsed and refractory B cell malignancies remain a therapeutic challenge, as these diseases are characterized by adverse survival. These cancers share a cell origin from the B-cell lineage and consequent surface expression of B-lineage markers such as CD19 and CD22. Chimeric antigen receptor (CAR) engineered T cell therapy has recently emerged as a new modality to target B cell malignancies. CARs couple a single-chain Fv (scFv) domain directed against a B-lineage-specific antigen to T-cell activating intracellular signaling domains. CAR gene-modified T cell interaction with target cells occurs in a HLA-independent fashion, so that a single vector can be used to treat all patients with cancers that express the target antigen. Miltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies. Closed-system operation, improved robustness, simplified work flows, and reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows for decentralized manufacturing. In the proposed phase II study, the investigator will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies.

Conditions

Precursor B-Lymphoblastic Lymphoma/Leukaemia Refractory

Keywords

B cell Acute Lymphoblastic Leukemia; relapsed or refractory; CD-19 Positive

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  ORR in ALL patients is defined as the rate of complete remission (CR, CRh) on day 28

  1 Month

Secondary Outcomes (3)

• Overall incidence and severity of adverse events.

  1 Months

• Rate of ALL patients achieving MRD negative CR

  12 Months

• Relapse rate and time to relapse

  12 Months

Other Outcomes (2)

• Disease-free and overall survival at 1 year after adoptive immunotherapy with MB-CART19.1 in patients not receiving alloSCT

  12 Months

• Level of circulating CAR T cells

  12 Months

Study Arms (1)

CRA treatment

EXPERIMENTAL

The drug for this trial is autologous T cells transduced with the lentiviral vector pLTG1563 (MB-CART19.1). The dose is 2x10e6 \~2x10e7 MB-CART19.1/kg. A leukapheresis for the patient will be performed for MB-CART19.1 generation. All patients will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2/d intravenously (iv) on days -5,-4,-3 and -2 cyclophosphamide 500 mg/m2/d iv on day -3,-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells.

Drug: MB-CART19.1

Interventions

MB-CART19.1 DRUG

Miltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies. Closed-system operation, improved robustness, simplified work flows, and reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows for decentralized manufacturing. In this study, we will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies.

Also known as: Miltenyi CD-19 CAT-T cell

CRA treatment

Eligibility Criteria

• Age: 2 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≤18 years (if deemed fit by treating investigator)
• CD19 expression must be detected on the malignant cells by flow cytometry.
• Patients with relapsed disease with \>5% blasts in BM (M2 or M3) after at least one standard chemotherapy and one salvage regimen who are ineligible for allogeneic stem cell transplant (alloSCT)
• Patients have refractory disease activity precluding alloSCT at this time, or patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
• Patients and/or parents must give their written informed consent/assent.

You may not qualify if:

• Rapidly progressive disease that in the estimation of live less than 12 weeks
• Isolated extramedullary relapse (CNS and/or testicular) in ALL
• Current autoimmune disease, or history of autoimmune disease with potential CNS involvement
• Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
• History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years.
• Pulmonary function: Patients with pre-existing severe lung disease (FEV1 or FVC \< 65%) or an oxygen requirement of \>28% O2 supplementation or active pulmonary infiltrates on chest X-ray at the time scheduled for T cell infusion
• Cardiac function: Fractional shortening \<28% or left ventricular ejection fraction \<50% by echocardiography
• Renal function: Creatinine clearance \<50 mL/min/1.73 m2

Sponsors & Collaborators

• Shanghai Children's Medical Center: lead
• Miltenyi Biomedicine GmbH: collaborator

MeSH Terms

Conditions

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jing Chen, MD,PhD

  Shanghai Children Medicine Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing Chen, MD, PhD

CONTACT

86 18930830632; chenjing@scmc.com.cn

Benshang Li, MD, PhD

CONTACT

86 18101893712; libenshang@scmc.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: October 25, 2017
• Study Start: December 1, 2017
• Primary Completion: July 1, 2019
• Study Completion: December 31, 2019
• Last Updated: October 25, 2017

Record last verified: 2017-10