A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

NCT04230473 | Completed Phase 1

• 1 other identifier: HY-CD19 CART-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of CNCT19 in adult patients with relapsed or refractory acute lymphoblastic leukemia.

Conditions

Relapsed or Refractory Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)

  Determine the MTD and DLT of CNCT19 in the Treatment and recommend the dose for Phase II study.

  28 days

• Safety of CNCT19 therapy

  Safety measures include adverse events as assessed by CTCAE v5.0.

  24 months

Secondary Outcomes (9)

• Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)

  3 months

• Overall Remission Rate (ORR)

  28 days

• Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow

  28 days

• Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow

  3 months

• Overall Remission Rate (ORR)

  6 months

Study Arms (1)

Single dose of CNCT19

EXPERIMENTAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.

Biological: single dose of CNCT19

Interventions

single dose of CNCT19 BIOLOGICAL

Dose A: 0.25 x 10\^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide Dose B: 1.00 x 10\^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide Dose C: 2.00 x 10\^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide

Single dose of CNCT19

Eligibility Criteria

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

You may qualify if:

• Informed consent is signed by the subject.
• Age 18 to 65.
• Relapsed or refractory ALL
• Relapse within 12 months of first remission;
• Without remission after more than 6 weeks of induction chemotherapy or without remission after 2 cycles of induction chemotherapy regimen;
• nd or greater Bone Marrow (BM) relapse OR;
• First relapse after chemotherapy, without remission after at least 1 rescue treatment;
• Any BM relapse after autologous stem cell transplantation (SCT).
• Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months of study entry.
• Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 1 generation and/or 2 generation of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a T315I mutation.
• Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
• Eastern cooperative oncology group (ECOG) performance status of 0 to 1.
• Adequate organ function defined as:
• aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN);
• Serum alanine aminotransferase (ALT) ≤ 3 upper limit of normal (ULN);

You may not qualify if:

• Active CNS involvement by malignancy.
• Isolated extra-medullary disease relapse.
• Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The following situations are excluded:
• Lymphodepleting Chemotherapy prescribed by the protocol;
• Tyrosine kinase inhibitors (TKI) and hydroxyurea must be stopped \> 72 hours prior to CNCT19 infusion;
• The following drugs must be stopped \> 1 week prior to CNCT19 infusion: 6-mercaptopurine, 6-thioguanine, methotrexate (\<25 mg / m2), cytosine arabinoside (\<100 mg / m2 / d), vincristine, asparaginase;
• Pegylated-asparaginase must be stopped \> 4 weeks prior to CNCT19 infusion;
• CNS prophylaxis treatment must be stopped \> 1 week prior to CNCT19 infusion.
• Radiotherapy before CNCT19 infusion:
• Non-CNS site of radiation completed \< 2 weeks prior to CNCT19 infusion; CNS directed radiation completed \< 8 weeks prior to CNCT19 infusion.
• Therapeutic systemic doses of steroids were stopped \< 72 hours prior to CNCT19 infusion. However, the following physiological replacement doses of steroids are allowed: \< 10 mg/day hydrocortisone or equivalent.
• Has had treatment with any prior CAR-T therapy.
• Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• Patients with systemic vasculitis (such as Wegener granulomatosis, nodular polyarteritis, systemic lupus erythematosus) and active or uncontrolled autoimmune disease (such as autoimmune hemolytic anemia, etc.).
• Patients who are positive for any of HBsAg, HBeAg, HBeAb, HBcAb, HCV-Ab, TP-Ab.

Sponsors & Collaborators

• Juventas Cell Therapy Ltd.: lead

Study Sites (2)

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

Institute of Hematology & Blood Diseases Hospital

Tianjin, 300020, China

Location

MeSH Terms

Conditions

Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jianxiang Wang, Dr.

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 11, 2020
• First Posted: January 18, 2020
• Study Start: March 13, 2020
• Primary Completion: December 1, 2020
• Study Completion: November 1, 2022
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

CN (2)