Safety and Efficacy of iPD1 CD19 eCAR T Cells in Relapsed or Refractory B-cell Lymphoma

NCT03208556 | Unknown Phase 1 DMC

• 1 other identifier: 2017YJZ13
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

PD1 pathway is critical in determining the response to CAR T cell therapy. Emerging data suggested that Inhibition of PD1 could enhance the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells is an enhanced version of the classical 2nd generation anti-CD19 4-1BB-costimulatory chimeric antigen receptor engineered T cells with cell-intrinsic PD1 inhibition by incorporation of a PD1 shRNA-expressing cassette in the CAR lentivector. This design will enhance the anti-tumor activities of CAR T cells by inhibiting PD1 induction after CAR T cell activation. This pilot, single arm, one center, dose-escalation, open label study is to determine the safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory CD19 positive lymphoma. Subjects will be given a lymphodepletion chemotherapy comprised of Fludarabine and cyclophosphamide prior to CAR T cell infusion. The chemotherapy is completed 1 to 4 days before the first dost of iPD1 CD19 eCAR T cells.

Conditions

Relapsed or Refractory B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0

  incidents of treatment related adverse events per NCI CTCAE V4.0

  2 years

Secondary Outcomes (3)

• treatment response

  6 months

• overall survival

  3 years

• progression-free survival

  2 years

Other Outcomes (2)

• Persistence of iPD1 CD19 eCAR T cells in patients

  2 years

• proliferation of iPD1 CD19 eCAR T cells in patients

  6 months

Study Arms (1)

iPD1 CD19 eCAR T cells

EXPERIMENTAL

patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion

Biological: iPD1 CD19 eCAR T cells; Drug: Fludarabine and cyclophosphamide

Interventions

iPD1 CD19 eCAR T cells BIOLOGICAL

iPD1 CD19 eCAR T cells are administrated in a 3-day split-dose regimen （d0, 30%; d1, 30%; d2, 40%）. CAR T cell dose escalation: 1×10\^5 /kg，1×10\^6 /kg，3×10\^6 /kg，and 6×10\^6 CAR T cells/kg

iPD1 CD19 eCAR T cells

Fludarabine and cyclophosphamide DRUG

Fludarabine 25 mg/m2 d1-3; cyclophosphamide 250 mg/m2 d1-3. Lymphodepletion chemotherapy is completed 1 to 4 days before CAR T cell infusion

iPD1 CD19 eCAR T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CD19+ B cell lymphoma,verified by IHC or flow cytometry.
• a prior history of at least one standard care of medication.
• ineligible for allogeneic transplantation or relapsed after transplantation.
• patients are 18 years older.
• life expectancy \> 3months.
• ECOG ≤ 2.
• satisfactory major organ functions: adequate heart function with LVEF≥50%; pulse oximetry of ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl .
• Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10\^9/L, PLT ≥ 50×10\^9/L.
• women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study.
• measurable tumors.

You may not qualify if:

• using immunosuppressive drugs or systemic steroids within one week of enrollment.
• active infection.
• HIV positive.
• active hepatitis B virus infection or hepatitis C virus infection.
• breastfeeding or pregnant women.
• patients refuse to practice birth control during study and one year post study.
• patients with a prior history of other malignances will be excluded from this study, but patients who have been cured from skin basal cell carcinoma or cervical cancer, or who have had their tumors removed by surgical resection but without further therapies and have more than 5 years of progression-free survival, can be included into the study.
• currently enrolled in other study.
• patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.

Sponsors & Collaborators

• Peking University: lead
• Marino Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Beijing Cancer Hosptical

Beijing, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jun Zhu, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

• Zhitao Ying, MD

  Peking University Cancer Hospital & Institute

  STUDY DIRECTOR

• Xiaoyu Xiang, PhD

  Marino Biotechnology Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Jun Zhu, MD

CONTACT

+86-10-88196596; zj@bjcancer.org

Zhitao Ying, MD

CONTACT

yingzhitao001@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: July 5, 2017
• Study Start: June 21, 2017
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: September 14, 2017

Record last verified: 2017-07

Locations

CN (1)