Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma

NCT04029038 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: 2019-0042NCI-2019-04229P30CA016672
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does not respond to treatment (refractory). T-cells are collected from the patient and genetic materials called "chimeric antigen receptors (CAR)" are transferred to the collected T-cells. The CAR T-cells are then infused back to the patient's body. Giving CD19- CD22 CAR T cells after chemotherapy may help to control the disease.

Conditions

CD19 Positive; CD22 Positive; Minimal Residual Disease; Progressive Disease; Recurrent B Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Refractory B Acute Lymphoblastic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Optimal chimeric antigen receptor (CAR) T cell dose level

  Dose-finding will be done using the sequentially adaptive phase I-II EffTox method.

  Up to 30 days

• Incidence of adverse events (adverse events)

  Toxicity is defined as a grade 3, 4, or 5 cytokine release syndrome, neurotoxicity, or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 with onset within 30 days of cell infusion. Adverse events that are considered disease-related (not suspected of relationship to CD19-CD22 -CAR T cells) will not be considered dose-limiting toxicities. Only those AEs that occur during the first 30 days after infusion, which are suspected to be related to conditioning lymphodepletion chemotherapy regimen and/or CD19 -CD22-CAR T cells (any component of the treatment regimen), and meet the following criteria, will be used in the definition of toxicity. Hematologic toxicities will not be considered in the definition of toxicity, as pancytopenia is a common toxicity with this regimen.

  Up to 30 days

• Efficacy in complete response (CR) or partial response

  Efficacy is defined as the patient being alive and in complete response (CR) or partial response (PR) at day 30 post cell infusion.

  Day 30 post cell infusion

Secondary Outcomes (2)

• Progression-free survival

  Up to 1 year post T-cell infusion

• Overall survival

  Up to 1 year post T-cell infusion

Other Outcomes (2)

• Immune reconstitution

  Up to 1 year post T-cell infusion

• Persistence of CAR T-cells

  Up to 1 year post T-cell infusion

Study Arms (1)

Treatment (CD19-CD22 CAR T cells)

EXPERIMENTAL

Patients receive standard of care cyclophosphamide IV over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells.

Biological: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Autologous CD19/CD22 Chimeric Antigen Receptor T-cells BIOLOGICAL

Given IV

Also known as: Autologous Anti-CD19/CD22 CAR-T Cells, Autologous CD19/CD22 CAR T Cells, Autologous CD19/CD22 CAR T-cells, Autologous CD19/CD22 Chimeric Antigen Receptor T Cells

Treatment (CD19-CD22 CAR T cells)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (CD19-CD22 CAR T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (CD19-CD22 CAR T cells)

Eligibility Criteria

• Age: 6 Months - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed/refractory B-acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), or non-Hodgkin's lymphoma (NHL) treated with at least two lines of therapy, and have persistent or progressed disease including positive minimal residual disease (MRD)
• Patients may have received last cytotoxic chemotherapy at least 3 weeks prior to lymphodepleting chemotherapy
• Patient may continue targeted therapy until 2 weeks before initiation of lymphodepleting chemotherapy with the exception of ibrutinib
• Disease must be CD19 and/or CD22 positive by flow cytometry or immunohistochemistry
• Karnofsky/Lansky performance scale \> 70
• Total bilirubin less than \< 1.5 mg/dL except patients with Gilbert syndrome whose total bilirubin must be \< 3.0mg/dL
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 2.5 X upper limit of normal (ULN)
• Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 5.0 ULN
• Serum creatinine (as estimated by Cockcroft Gault) \>= 60 cc/min
• Cardiac ejection fraction \>= 50% without evidence of pericardiac effusion as determined by echocardiogram (ECHO) or multigated acquisition scan (MUGA), no clinical significant electrocardiogram (ECG) findings
• No clinical significant pleural effusion and baseline oxygen saturation \>= 92%
• Absolute lymphocyte count \>= 100/ul
• Be able to sign informed consent
• All participants who are able to have children must practice effective birth control while on study. Acceptable forms of birth control for female patients include: birth control pills, patches, or injections, intrauterine device (IUD), diaphragm with spermicide, or condom with spermicide. Acceptable forms of birth control for male patients include condom with spermicide. If female participant becomes pregnant during the study, she will be taken off this study. If male participant fathers a child while on study, he must immediately notify his doctor
• For patients with history of allogenic stem cell transplantation

You may not qualify if:

• Positive beta-human chorionic gonadotropin (hCG) in female of child bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females
• Known positive serology for human immunodeficiency virus (HIV)
• Presence of active grade 3 or greater toxicity from the previous treatment
• Presence of active fungal, bacterial, viral, or other infection requiring IV antibiotics for management
• Presence of active neurologic disorders
• Concomitant use of other investigational agents
• Current use of corticosteroid more than physiological dose for adrenal insufficiency (prednisone equivalent at a dose higher than 10 mg/day)
• Presence of active CNS disease

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm, Residual; Disease Progression; Burkitt Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jin S Im

  M.D. Anderson Cancer Center

  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: July 19, 2019
• First Posted: July 23, 2019
• Study Start: May 15, 2019
• Primary Completion: November 16, 2022
• Study Completion: November 16, 2022
• Last Updated: August 21, 2023

Record last verified: 2023-08

Locations

US (1)