huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

NCT03103971 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: 9364NCI-2017-00421RG9217000
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of huJCAR014 in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a molecule CD19 on their surfaces. In Stage 1, dose-finding studies will be conducted in 3 cohorts:

1. 1.Aggressive B cell NHL
2. 2.Low burden ALL
3. 3.High burden ALL
4. 4.Cohort 2A, CAR-naïve (n=10): patients who have never received CD19 CAR-T cell therapy.
5. 5.Cohort 2B, CAR-exposed (n=27): patients who have previously failed CD19 CAR-T cell therapy.

Conditions

Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Recurrent Transformed Non-Hodgkin Lymphoma; Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Recurrent B Acute Lymphoblastic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Refractory B Acute Lymphoblastic Leukemia; Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements

Outcome Measures

Primary Outcomes (6)

• Incidence of toxicity

  Will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.

  Up to 30 days after the final dose of study therapy

• Dose-limiting toxicity (DLT) rates

  Observed DLT rates will be summarized based on the DLT-Evaluable analysis set. Final DLT rates at each dose level will be estimated by isotonic regression.

  Up to 28 days

• Maximum concentration (Cmax) of autologous human anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes (huJCAR014) cells in blood

  huJCAR014 will be measured in blood using quantitative polymerase chain reaction (PCR) (qPCR) and flow cytometry over 28 days after huJCAR014 infusion. Cmax is the peak concentration of huJCAR014 cells in blood in the first 28 days after infusion.

  Up to 28 days

• Time to maximum concentration (Tmax), of huJCAR014 cells in blood

  huJCAR014 will be measured in blood using quantitative PCR (qPCR) and flow cytometry over 28 days after huJCAR014 infusion. Tmax is the time to reach the maximum concentration of huJCAR014 cells in blood in the first 28 days.

  Up to 28 days

• Area under the curve of huJCAR014 cells in blood

  huJCAR014 will be measured in blood using quantitative PCR (qPCR) and flow cytometry over 28 days after huJCAR014 infusion. AUC is the calculated area under the curve of huJCAR014 concentrations in blood by time after infusion through 28 days.

  Up to 28 days

• Presence of huJCAR014 cells in bone marrow

  The persistence of huJCAR014 in the bone marrow at 28 days will be assessed, based on both a qPCR assay and flow cytometry.

  Up to 28 days

Secondary Outcomes (7)

• Complete response (CR) rate

  Up to 15 years

• Partial response (PR) rate

  Up to 15 years

• Objective response rate (ORR)

  Up to 15 years

• Duration of response (DOR)

  Up to 15 years

• Progression-free survival (PFS)

  From date of first huJCAR014 infusion to progressive disease or death, assessed up to 15 years

Other Outcomes (7)

• Cellular immune responses to huJCAR014

  Up to 1 year

• B-cell depletion in circulation

  Up to 1 year

• Cytokine profile

  Up to 1 year

Study Arms (1)

Treatment (leukapheresis, chemotherapy, huJCAR014)

EXPERIMENTAL

Patients undergo leukapheresis. Beginning 14-16 days after leukapheresis, patients undergo lymphodepleting chemotherapy comprising either cyclophosphamide IV daily for 1 day and fludarabine IV daily for 3 days or cyclophosphamide and fludarabine IV daily for 3 days. Within 36-96 hours after completion of lymphodepleting chemotherapy, patients receive huJCAR014 IV over 20-30 minutes on day 0.

Biological: Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes; Drug: Cyclophosphamide; Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis; Other: Pharmacological Study

Interventions

Autologous Human Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes BIOLOGICAL

Given IV

Also known as: Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes huJCAR014, Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes huJCAR014, Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes, huJCAR014

Treatment (leukapheresis, chemotherapy, huJCAR014)

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 (leukapheresis, chemotherapy, huJCAR014)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (leukapheresis, chemotherapy, huJCAR014)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (leukapheresis, chemotherapy, huJCAR014)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (leukapheresis, chemotherapy, huJCAR014)

Pharmacological Study OTHER

Correlative studies

Treatment (leukapheresis, chemotherapy, huJCAR014)

Eligibility Criteria

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

You may qualify if:

• Male or female \>= 18 years of age at the time of screening consent
• Diagnosis of R/R B-cell NHL or ALL as defined below:
• Relapsed or refractory B-cell NHL meeting all of the following criteria:
• Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; LBCL transformed from any indolent histology; or primary mediastinal B-cell lymphoma (PMBCL)
• Prior treatment with an anthracycline and rituximab or another CD20-targeted agent (unless the disease is CD20-negative); transformed DLBCL (tDLBCL) must have failed treatment for DLBCL
• At least one of the following:
• Refractory disease after frontline chemo-immunotherapy
• Not eligible for autologous hematopoietic stem cell transplant (auto-HSCT)
• Relapsed or refractory disease after at least 2 lines of therapy or after auto-HSCT
• Relapsed or refractory disease after allogeneic hematopoietic stem cell transplant (allo-HSCT)
• Relapsed or refractory B-cell ALL (patients with Burkitt's lymphoma/leukemia are not eligible)
• All B-ALL patients must have detectable disease by morphology, flow cytometry, cytogenetic analysis (e.g. polymerase chain reaction \[PCR\], fluorescence in situ hybridization \[FISH\], karyotyping) or imaging (e.g. positron emission tomography \[PET\]/computed tomography \[CT\]) or a high likelihood of active disease
• Refractory: failure to achieve complete response (CR) (minimal residual disease \[MRD\]-negative) at the end of induction
• Relapsed: recurrence of disease after achieving CR
• Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology

You may not qualify if:

• For patients in stage 1 only, prior treatment with any CD19 CAR T-cell therapy is excluded
• Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
• Pregnant or breastfeeding women
• Any known contraindication to leukapheresis
• Any known and irreversible contraindication to huJCAR014 therapy
• Medical, psychological, familial, sociological, or geographical condition that does not permit compliance with the protocol as judged by the PI or designee, or unwillingness or inability to follow protocol procedures
• History or presence of clinically relevant central nervous system (CNS) pathology that, in the opinion of the PI or designee, is a contraindication to lymphodepleting chemotherapy or huJCAR014 infusion
• History of another primary malignancy that has not been in remission for at least 2 years with the following exceptions: nonmelanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, or other malignancy considered by the investigator to have a low risk of relapse or progression
• Active autoimmune disease requiring immunosuppressive therapy, unless considered by the PI or designee to be eligible
• Presence of active acute or chronic graft versus host disease (GVHD)
• Use of any of the following:
• Cytotoxic or lymphotoxic agents (including prednisone \> 5 mg/day or equivalent corticosteroid) within 1 week prior to leukapheresis; physiologic corticosteroid replacement, and topical or inhaled corticosteroids are not excluded
• GVHD therapies within 4 weeks prior to leukapheresis (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL-6, or anti-IL-6R)
• Experimental agents within 4 weeks prior to leukapheresis unless progression is documented on therapy and at least 3 half-lives have elapsed prior to leukapheresis
• Radiation encompassing all sites of known tumor within 6 weeks prior to leukapheresis, unless there is evidence of active disease after radiation by imaging, biopsy or clinical evaluation

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Juno Therapeutics, Inc., a Bristol-Myers Squibb Company: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Gauthier J, Liang EC, Huang JJ, Kimble EL, Hirayama AV, Fiorenza S, Voutsinas JM, Wu QV, Jaeger-Ruckstuhl CA, Pender BS, Kirchmeier DR, Torkelson A, Braathen K, Basom R, Shadman M, Kopmar NE, Cassaday RD, Riddell SR, Maloney DG, Turtle CJ. Phase 1 study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naive adult patients with B-ALL. Blood Adv. 2025 Apr 22;9(8):1861-1872. doi: 10.1182/bloodadvances.2024015314.

  PMID: 39820359 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Burkitt Lymphoma

Interventions

Cyclophosphamide; fludarabine; Leukapheresis

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Jordan Gauthier

  Fred Hutch/University of Washington Cancer Consortium

  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: March 27, 2017
• First Posted: April 7, 2017
• Study Start: November 3, 2017
• Primary Completion: March 23, 2023
• Study Completion: March 23, 2024
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)