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Administration of Autologous CAR-T CD19 Antigen With Inducible Safety Switch in Patients With Relapsed/Refractory ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03016377
Recruitment Status : Recruiting
First Posted : January 10, 2017
Last Update Posted : February 24, 2020
Sponsor:
Collaborator:
Bellicum Pharmaceuticals
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:

The body has different ways of fighting infection and disease. No single way is effective at fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study combines both T cells and antibodies to try to create a more effective treatment. This investigational treatment is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD19 antigen (ATLCAR.CD19) administration.

In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying your genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells makes a piece of an antibody called anti-CD19. This antibody can flow through the blood and can find and stick to leukemia cells because these leukemia cells have a substance on their surface called CD19. Anti-CD19 antibodies have been used to treat people with leukemia but have not been strong enough to cure most patients. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood a piece of it is now joined to the surface of the T cells. Only the part of the antibody that sticks to the leukemia cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD19 chimeric (combination) receptor-activated T cells kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.

Preliminary results of giving ATLCAR.CD19 cells to leukemia patients have been encouraging; however, many subjects receiving this treatment have experienced unwanted side effects including neurotoxicity and/or cytokine release syndrome (also referred to as cytokine storm or an infusion reaction). Cytokines are small proteins that aract as e signals to other cells and are the way cells talk to one another. During cytokine release syndromesyndrome, too many cytokines are released and too many cells in your body react to their release. Symptoms resulting from cytokine release syndrome vary from flu-like symptoms to more severe side effects such as cardiac arrest, multi-system organ failure or death. We predict that about 50% of patients on this study will experience mild to severe cytokine release syndrome.

To help reduce cytokine release syndrome symptoms in future patients, a safety switch has been added to the ATLCAR.CD19 cells that can cause the cells to become dormant or "go to sleep". The safety switch is called inducible caspase 9 or iC9. The modified ATLCAR.CD19 cells with the safety switch are referred to as iC9-CAR19 cells.

The purpose of this study is to determine whether receiving the iC9-CAR19 cells is safe and tolerable (there are not too many unwanted effects). If you experience severe cytokine release syndrome or moderate to severe cytokine release syndrome that does not get better once you are given standard treatments, you may be given a second study drug called rimiducid. Similar studies showed that rimiducid can to turn on the safety switch, iC9 in other therapies. Using rimiducid to activate the safety switch may be done in addition to treating you according to hospital guidelines and making all efforts to immediately attend to your cytokine release syndrome symptoms


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Immune System Diseases Immunoproliferative Disorders Biological: iC9-CAR19 cells Drug: Rimiducid Drug: Cyclophosphamide Drug: Fludarabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Administration of Autologous CAR-T Cells Targeting the CD19 Antigen and Containing the Inducible caspase9 Safety Switch in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia
Actual Study Start Date : March 22, 2018
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : October 2036


Arm Intervention/treatment
Experimental: iC9-CAR19 cells
The 3+3 design in adult subjects and an independent study using 3+3 design in pediatric subjects. The starting dose of 5 x 10^5 transduced cells/kg will enroll 3 adult subjects in the initial cohort. If there are no dose limiting toxicities w/in 4 weeks of the cell infusion in these 3 subjects, then the next cohort will evaluate 1 x10^6 transduced cells/kg in adults. If there is toxicity in 1/3 patients in the initial cohort, the cohort will be expanded to enroll up to 6 adult patients. If the dose level 1 is determined to be above the tolerated cell dose, de-escalation would occur to dose level -1 where subjects would receive 1 x 10^5 transduced cells/kg. All subjects will receive a lymphodepleting regimen of fludarabine and cyclophosphamide before administration of iC9-CAR19 T cells.
Biological: iC9-CAR19 cells
Three dose levels are being evaluated: dose level -1 (1 x 10^5), dose level 1 (5 x 10^5), and dose level 2 ( 1x 10^6)
Other Name: CAR.CD19 T cells

Drug: Rimiducid
Subjects who develop grade 4 CRS or grade 2/3 CRS that is unresponsive to standard of care interventions will be given Rimiducid at .4 mg/kg.
Other Name: AP1903

Drug: Cyclophosphamide
900 mg/m^2 IV over 1 hour on day 4 of lymphodepleting chemotherapy.
Other Name: Neosar

Drug: Fludarabine
25 mg/m^2/day IV over 30 minutes administered for 3 consecutive days.
Other Name: Fludara

Experimental: Expansion Cohort Second Administration of iC9-CAR19 cells
After the recommended phase 2 dose (RP2D) of iC9-CAR19 T cells has been determined in adults, up to 18 additional adult subjects will be enrolled in an expansion cohort at the RP2D. In the expansion cohort, subjects will be offered a second infusion of iC9-CAR19 T cells based on B-cell recovery and minimal residual disease (MRD) status. All subjects will receive a lymphodepleting regimen of fludarabine and cyclophosphamide before second administration of iC9-CAR19 T cells.
Biological: iC9-CAR19 cells
Three dose levels are being evaluated: dose level -1 (1 x 10^5), dose level 1 (5 x 10^5), and dose level 2 ( 1x 10^6)
Other Name: CAR.CD19 T cells

Drug: Rimiducid
Subjects who develop grade 4 CRS or grade 2/3 CRS that is unresponsive to standard of care interventions will be given Rimiducid at .4 mg/kg.
Other Name: AP1903

Drug: Cyclophosphamide
900 mg/m^2 IV over 1 hour on day 4 of lymphodepleting chemotherapy.
Other Name: Neosar

Drug: Fludarabine
25 mg/m^2/day IV over 30 minutes administered for 3 consecutive days.
Other Name: Fludara




Primary Outcome Measures :
  1. Number of participants with adverse events as a measure of safety and tolerability of iC9-CAR19 T cells [ Time Frame: 4 weeks ]
    Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (AEs) (CTCAE, version 5.0), a descriptive terminology which can be utilized for AE reporting. A grading (severity) scale is provided for each AE term/symptom: Grade 1 (Mild; asymptomatic); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE). Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).


Secondary Outcome Measures :
  1. Incidence of dose limiting toxicity to identify recommended phase 2 dose (RP2D) [ Time Frame: 4 weeks ]
    The recommended phase 2 dose of iC9-CAR19 cells in adult and pediatric subjects will be determined maximum dose at which no more than one out of six patients experiences a dose limiting toxicity (DLT). A DLT is defined according to protocol criteria using the NCI CTCAE, ICANS, and CRS criteria. In general, a DLT is any grade 3 or higher event that is at least possibly related to iC9-CAR19 T cells.

  2. Changes in persistence of iC9-CAR19 T cells in vivo [ Time Frame: 15 years ]
    Persistence of iC9-CAR19 T cells in vivo will be determined by quantitative polymerase chain reaction (PCR) and flow cytometry in samples of peripheral blood.

  3. Overall Response Rate (ORR) [ Time Frame: 15 years ]
    ORR (Complete Response/Complete Response with incomplete recovery of counts) to first iC9-CAR19 T cell therapy will be determined using National Comprehensive Cancer Network Response Criteria (NCCN) for acute lymphoblastic leukemia. Assessment of minimal residual disease will be included as criterion of response (ie, the percentage of subjects who achieve CRm [defined as minimal residual disease negative complete response] by either flow cytometry or PCR analysis will be determined)

  4. Overall survival after infusion of iC9-CAR19 T cells [ Time Frame: 15 years ]
    Overall survival will be measured from the date of administration of first iC9-CAR19 T cells to the date of death.

  5. Event-free survival rate [ Time Frame: 15 years ]
    Event free survival rate applies to all subjects and will be measured from the date of administration of first iC9-CAR19 T cells to the date of signs and symptoms of treatment failure or relapse from complete response or complete response with incomplete recovery of counts, or death from any cause; subjects not known to have any of these events are censored on the date they were last examined.

  6. Relapse-free survival rate [ Time Frame: 15 years ]
    Relapse-free survival rate will apply only to subjects achieving complete response or complete response with incomplete recovery of counts and measured from the date of achievement of a remission until the date of relapse or death from any cause; subjects not known to have relapsed or died at last follow-up are censored on the date they were last examined.

  7. Incidence of patient reported symptoms in adult patients using selected symptoms from the NCI PRO-CTCAE [ Time Frame: 15 years ]
    The NCI Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a patient-reported outcome measurement system developed to characterize the frequency, severity and interference of 78 symptomatic treatment toxicities.

  8. Changes in patient reported physical functions in adult patients [ Time Frame: 15 years ]
    Patient reported physical functions in adult patients will be assessed per the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score derived from the PROMIS Physical Function Short Form 20a v1.0. PROMIS is a set of person-centered measures, developed by the US Department of Health and Human Services, that evaluates and monitors physical, mental, and social health on a five point Likert scale with higher score indicating better functioning.

  9. Changes in patient reported health-related quality of life in adult patients [ Time Frame: 15 years ]
    Patient reported health-related quality of life will be assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Global Health Score derived from the PROMIS Global Health Short Form v1.0-1.1. PROMIS is a set of person-centered measures, developed by the US Department of Health and Human Services, that evaluates and monitors physical, mental, and social health health on a five point Likert scale with higher score indicating better functioning.

  10. Number of participants with adverse events as a measure of safety and tolerability of a second infusion of iC9-CAR19 T cells [ Time Frame: 4 weeks ]
    Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (AEs) (CTCAE, version 5.0), a descriptive terminology which can be utilized for AE reporting. A grading (severity) scale is provided for each AE term/symptom: Grade 1 (Mild; asymptomatic); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE). Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).

  11. Rate of measurable residual disease (MRD) clearance in subjects who receive iC9-CAR19 T cells for MRD persistence or MRD-only relapse [ Time Frame: 8 weeks ]
    Rate of MRD clearance will be defined as the proportion of subjects who enter MRD-negative complete response (CRm) who are treated with one or two infusions of iC9 CAR19 T cells at the time of being in complete response (CR) or Complete Response with incomplete recovery of counts (CRi), but not CRm.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria - Cell Procurement

  • Written informed consent for procurement signed by subject/legal guardian of pediatric subject and HIPAA authorization
  • Age 3-17 years of age for pediatric subjects (weight must be ≥10 kg), ≥18-70 years of age for adults at time of consent
  • Karnofsky score >60% (≥16 years old), Lansky performance score of >60% (<16 years old)
  • Relapsed or refractory (R/R) precursor B cell ALL:

    • 2nd or greater bone marrow relapse, or
    • Any bone marrow relapse >100 days after allogeneic stem cell transplant, or
    • Primary refractory ALL defined as no complete response (CR) after 2 cycles of standard of care chemotherapy regimen, or
    • For adult subjects: 1st bone marrow relapse with 1st CR <1 year, or CR1 ≥1 year and refractory to ≥1 cycle of therapy for relapse
    • Subjects with isolated non-CNS extramedullary disease will be eligible as long as the time-of-remission criteria (above) are met and biopsy for extramedullary disease confirms CD19 expression
    • For pediatric subjects: 1st bone marrow or isolated non-CNS extramedullary relapse refractory to 1 cycle of standard therapy for relapsed ALL
    • While active CNS3 leukemia is excluded, subjects with concurrent CNS3 disease and bone marrow relapse who responded to CNS-directed therapy prior to enrollment may participate. Intrathecal chemotherapy will be allowed to continue between lymphodepleting chemotherapy (LD) and cell infusion.
    • Subject with CNS2 disease and concurrent bone marrow relapse are eligible. Intrathecal chemotherapy will be allowed to continue between LD and cell infusion
    • Subject previously achieving remission with no detectable measurable residual disease (MRD) by multi-parameter flow cytometry, and who re-developed CD19+ MRD measured by multi-parameter flow cytometry will be eligible, provided the 1st MRD-negative CR was <1 year, MRD-negative CR1 duration ≥1 year and refractory to ≥1 cycle of therapy for MRD recurrence, or MRD reappearance occurs during 2nd/subsequent CR
    • Subject with persistent CD19+ MRD measured by multi-parameter flow cytometry after 3 cycles of initial chemotherapy, and have persistence of CD19+ MRD after ≥1 cycles of blinatumomab
  • Subject with Ph+ ALL will be eligible if failed ≥2 ABL tyrosine kinase inhibitors (TKI) or relapsed after allogeneic stem cell transplant, or have CD19+ MRD. Subject with the T315I ABL kinase point mutation eligible if have failed ponatinib-containing therapy, regardless of number of prior ABL TKIs
  • CD19 positivity of lymphoblasts confirmed by flow cytometry or IHC per institutional standards
  • Life expectancy ≥12 weeks
  • Demonstrate adequate renal and hepatic function as defined below:

System Laboratory Value Renal*: Serum Creatinine (sCr) ≤ 1.5 × ULN Hepatic: Total bilirubin (tBili) ≤ 1.5 × ULN, unless attributed to Gilbert's Syndrome; Aspartate aminotransferase (AST) ≤ 3.0 × ULN; Alanine aminotransferase (ALT) ≤ 3.0 × ULN

*For pediatric patients, adequate renal function defined below: Age: Maximum sCr (mg/dL) (Male, Female) 3 to <6 years: ≤0.8, ≤0.8; 6 to <10 years: ≤1, ≤1; 10 to <13 years: ≤1.2, ≤1.2; 13 to <16 years: ≤1.5, ≤1.4; 16 to <18 years: ≤1.7, ≤1.4

  • Females of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to procurement. Note: Females are considered of childbearing potential unless are premenarchal, surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are naturally postmenopausal for at least 12 consecutive months
  • Females and males of childbearing potential must be willing to abstain from heterosexual activity or to use 2 effective methods of contraception from informed consent until 3 months after end of treatment. The 2 contraception methods can be comprised of 2 barrier methods, or a barrier method plus a hormonal method. Female participants will inform their male partners that they must use the methods of birth control required by the protocol
  • Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the 1st dose of study therapy through 3 months after the last dose of study therapy. As determined by enrolling physician/designee, ability of subject to understand and comply with study procedures
  • Subject currently receiving "maintenance" doses of chemotherapy eligible and need for intrathecal prophylaxis prior to procurement is per investigator discretion. Maintenance doses of systemic chemotherapy are defined as methotrexate ≤30 mg/m2/week, mercaptopurine ≤100 mg/m2/day and vincristine ≤ 2 mg/28 days. Maintenance therapy in patients with Ph+ leukemia may also contain TKIs targeting BCR-ABL, at the discretion of the investigator. Corticosteroid-containing maintenance therapy is permitted only if corticosteroids are administered >14 days prior to procurement

Exclusion Criteria - Cell Procurement

  • Subject with relapsed fulminant CD19+ ALL rapidly progressing with circulating lymphoblasts that are rising in proportion to >50% of circulating white blood cells
  • Lumbar puncture must be performed prior to procurement and subject with evidence of CNS3 disease will be excluded from study entry. Subject with concurrent CNS3 disease and bone marrow relapse who responded to CNS-directed therapy prior to enrollment/LD allowed to participate. Subject with CNS2 disease and concurrent bone marrow relapse are eligible. Intrathecal chemotherapy will be allowed to continue between cell procurement and LD
  • Pregnant/breastfeeding (Note: breast milk cannot be stored for future use if collected while the mother is being treated on study)
  • Has known active and/or progressive additional malignancy requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, other cancer for which the subject has been disease-free for ≥5 years
  • Subject must not have tumor in a location where enlargement could cause airway obstruction
  • Subject may not have an oxygen requirement as defined by pulse oximetry of <90% on room air
  • Subject must not have left ventricular ejection fraction of <40% (shortening fraction <27% for pediatric subjects) as measured by echo or MUGA
  • Patient with the following infections will be excluded: active HIV, HTLV, HBV, HCV. Note: To meet eligibility subjects must not be positive for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for Hep B surface antigen, or negative for HCV antibody or HCV viral load
  • Patient on treatment for other active uncontrolled infections with resolution of signs/symptoms are not excluded. Non-influenza, non-RSV, isolated upper respiratory infections are not excluded. Other active uncontrolled infections will be excluded
  • Prior to procurement current use of systemic corticosteroids at doses ≥10 mg/day prednisone/equivalent; those receiving <10 mg/day may be enrolled at discretion of investigator. Corticosteroid use is contraindicated following iC9-CAR19 infusion unless medically necessary e.g., to treat CRS. Physiologic replacement with hydrocortisone is allowed at doses 6-12 mg/m2/day, or equivalent
  • Received anti-CD19 antibody-based therapy or cytotoxic chemotherapy not described as maintenance therapy in inclusion 4.1.12 within 2 weeks of procurement

Inclusion Criteria - Lymphodepletion (LD)

  • Written informed consent for the main study signed by subject/legal guardian of pediatric subject.
  • R/R precursor B cell ALL, confirmed by presence of blasts in the blood or bone marrow (≥5%) or in any extramedullary site. Subject who previously achieved remission with no detectable MRD by multi-parameter flow cytometry and re-developed CD19+ MRD measured by multi-parameter flow cytometry are eligible, provided 1st MRD-negative CR was <1 year, MRD-negative CR1 duration ≥1 year and refractory to ≥1 cycle of therapy for MRD recurrence/relapse, or MRD-recurrence in 2nd or subsequent morphologic CR. Subjects with persistent CD19+ MRD measured by multi-parameter flow cytometry after 3 cycles of initial chemotherapy and have persistence of CD19+ MRD after ≥1 cycles of blinatumomab are eligible
  • Karnofsky score >60%, (≥16 years old)/Lansky performance score >60% (if <16 years old)
  • Life expectancy ≥12 weeks
  • If prior therapy with murine antibodies must have documentation of absence of human anti-mouse antibodies (HAMA) prior to LD on this study
  • Demonstrate adequate renal and hepatic function as defined below System Laboratory Value Renal*: sCr ≤1.5 × ULN Hepatic: tBili ≤1.5 × ULN, unless attributed to Gilbert's Syndrome; AST ≤ 3.0 × ULN; ALT ≤3.0 × ULN

    *For pediatric patients, adequate renal function defined below: Age: Maximum sCr (mg/dL) (Male, Female) 3 to <6 years: ≤0.8, ≤0.8; 6 to <10 years: ≤1, ≤1; 10 to <13 years: ≤1.2, ≤1.2; 13 to <16 years: ≤1.5, ≤1.4; 16 to <18 years: ≤1.7, ≤1.4

  • WOCBP must have a negative serum pregnancy test
  • Females and males of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 3 months after treatment discontinuation. The 2 contraception methods can be comprised of 2 barrier methods, or a barrier method plus a hormonal method. Female participants will inform their male partners that they must use the methods of birth control required by the protocol
  • Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the 1st dose of study therapy through 3 months after the last dose of study therapy
  • As determined by the enrolling physician/designee, ability of the subject to understand and comply with study procedures
  • For subjects who receive chemotherapy between cell procurement and LD, washout periods between chemotherapy and the beginning of LD will be required
  • Subjects must have autologous transduced activated T cells that meet the Certificate of Analysis (CofA) acceptance criteria

Exclusion Criteria - Lymphodepletion (LD)

  • Pregnant/breastfeeding (Note: breast milk cannot be stored for future use if collected while the mother is being treated on study)
  • Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least 5 years
  • Subjects must not have tumor in a location where enlargement could cause airway obstruction
  • Subjects may not have an oxygen requirement as defined by pulse oximetry of <90% on room air
  • Treatment with any investigational drug within 14 days prior to LD or has received any tumor vaccines within the previous 5 weeks prior to LD
  • Subject received pegylated-asparaginase ≤3 weeks prior to LD
  • Radiotherapy to a non-CNS site completed <1 week prior to LD, or CNS directed radiation completed <7 weeks prior to LD
  • Subject receiving following drugs <1 week prior to LD: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside >100 mg/m2, anthracyclines, cyclophosphamide, methotrexate ≥25 mg/m2)
  • Any systemic drug used for GVHD must be stopped >3 weeks prior to LD (e.g. calcineurin inhibitors, methotrexate or other chemotherapy drugs, mycophenolyate, rapamycin, thalidomide, or immunosuppressive antibodies such as anti-CD20 (rituximab), anti-TNF, anti-IL6 or anti-IL6R, systemic steroids)
  • The following drugs must be stopped prior to the beginning of LD: TKIs, hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate <25 mg/m2, cytosine arabinoside <100 mg/m2/day, and asparaginase (non-pegylated). These drugs should not be administered concomitantly or following LD
  • CNS prophylaxis with intrathecal methotrexate, cytarabine and/or hydrocortisone treatment must be stopped prior to LD
  • Patients with the following systemic viral infections will be excluded: active HIV, HTLV, HBV, HCV. Note: To meet eligibility subjects are required to be negative for HIV antibody or HIV viral load, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for Hep B surface antigen, or negative for HCV antibody or HCV viral load
  • Patients who are on treatment for other active uncontrolled infections with resolution of signs/symptoms are not excluded. Non-influenza, non-RSV, isolated upper respiratory infections are not excluded. Other active uncontrolled infections will be excluded
  • Use of systemic corticosteroids at doses ≥10 mg/day prednisone or its equivalent; those receiving <10 mg/day may be enrolled at discretion of investigator. Physiologic replacement with hydrocortisone is allowed at 6-12 mg/m2/day, or equivalent

Inclusion Criteria- iC9-CAR19 Cell Infusion

  • Females and males of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from informed consent until 3 months after treatment discontinuation. The 2 contraception methods can be comprised of 2 barrier methods, or a barrier method plus a hormonal method. Female participants will inform their male partners that they must use the methods of birth control required by the protocol
  • Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with first dose of study therapy through 3 months after the last dose of study therapy
  • As determined by the enrolling physician/designee, ability of the subject to understand and comply with study procedures

Exclusion Criteria- iC9-CAR19 Cell Infusion

  • Corticosteroid use is contraindicated following iC9-CAR19 infusion unless medically necessary (e.g., to treat CRS)
  • Severe systemic uncontrolled disease or toxicities that develop after LD may prompt exclusion from cell infusion at the discretion of the investigator
  • Received any donor lymphocyte infusions (DLI) ≤6 weeks prior to cell infusion
  • Received any T cell lytic or toxic antibody (e.g. alemtuzumab) ≤8 weeks prior to cell infusion (residual lytic levels may destroy the infused iC9-CAR19 T cells and/or prevent their in vivo expansion)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03016377


Contacts
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Contact: Catherine Cheng (919) 445-4208 catherine_cheng@med.unc.edu
Contact: Spencer Laing (919) 445-4208 spencer.laing@med.unc.edu

Locations
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United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Catherine Cheng    919-445-4208    catherine_cheng@med.unc.edu   
Contact: Spencer Laing    (919) 445-4208    spencer.laing@med.unc.edu   
Principal Investigator: Matthew Foster, MD         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Bellicum Pharmaceuticals
Investigators
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Principal Investigator: Matthew Foster, MD Assistant Professor Hematology-Oncology

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Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03016377    
Other Study ID Numbers: LCCC 1541-ATL
First Posted: January 10, 2017    Key Record Dates
Last Update Posted: February 24, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
CAR T cells
CD19
Leukemia
T Lymphocytes
AP1903
Cytokine Release Syndrome
Rimiducid
ICANS
Immune effector cell mediated neurotoxicity syndrome
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites