Ensayos clínicos

Inclusion Criteria: 

• Patients eligible for inclusion in this study have to meet all of the following criteria:
  • Signed written informed consent, or signed parental permission form and assent form (as applicable), must be obtained prior to any study procedures.
  • CD19 expressing malignancy for which a CTL019 treatment protocol is currently enrolling or under IRB/EC review.
  • Hemoglobin level ≥ 9.0 g/dL at screening. Transfusion support can be provided within 24 hours of starting the leukapheresis procedure to meet this criterion.
  • Platelet count ≥ 50,000/microliter at screening. Transfusion support can be provided within 24 hours of starting the leukapheresis procedure to meet this criterion.
  • Prothrombin Time (PT)/ Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN at screening. Transfusion support can be provided within 24 hours of starting the leukapheresis procedure to meet this criterion.
  • Peripheral blood absolute lymphocyte count (ALC) ≥ 500/microliter at screening or if ALC <500/μL, then the absolute CD3 lymphocyte count must be ≥50/μL at screening.
  • For patients who have undergone allogeneic transplant, must be ≥3 months from allogeneic SCT at the time of leukapheresis.
  • Males and females weighing ≥10 kg who are eligible to undergo a PBMC collection by leukapheresis for potential future CTL019 manufacturing for use in a CTL019 trial.
• PBMC collection by leukapheresis is not recommended for patients < 3 years of age due to high manufacturing failure rates with leukapheresis collections performed at this age, unless a specific Novartis CTL019 treatment protocol is open for patients < 3 years of age.

Exclusion Criteria:

• Patients eligible for this study must not meet any of the following criteria:
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test at screening;
  • Human Immunodeficiency Virus (HIV) infection at screening;
  • Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) at screening;
  • Any patient that in the opinion of the investigator is not medically stable to undergo the leukapheresis procedure or will not comply with the visit schedules or procedures;
  • Treatment with any prior gene therapy product;
  • Patient has participated in a research study using an investigational agent within the last 30 days prior to screening;
  • Patient should not have received long-acting growth factors or drugs used for cell mobilization (e.g., Neulasta/pegflilgrastim) within 14 days of the leukapheresis procedure. Use of short-acting growth factors of drugs used for cell mobilization (e.g., G-CSF/Neupogen/filgrastim, plerixafor) must be ≥ 5 days of leukapheresis procedure.

The following treatments/medications are excluded:

• Chemotherapy
• Cytotoxic chemotherapy drugs must not be given within 2 weeks of leukapheresis.
• Intrathecal chemotherapy (IT): Recommend holding IT prior to leukapheresis collection. If clinically indicated, IT Ara-C may be given and leukapheresis collection started any time following IT Ara-C. Leukapheresis collection may be started ≥ 7 days after IT methotrexate (MTX).Pegylated-asparaginase must be stopped >4 weeks prior to leukapheresis
• Low dose daily or weekly maintenance chemotherapy should be stopped ≥ 2 weeks prior to leukapheresis.
• Clofarabine may be associated with prolonged lymphopenia. This should be taken into consideration when evaluation the optimal timing for leukapheresis collection. An interval of ≥8 weeks from the patient’s last clofarabine treatment is recommended.
• Short-acting drugs(e.g tyrosine kinase inhibitors, ibrutinib and hydroxyurea) must not be given within a 72 hour window of the leukapheresis procedure.

• Steroids
• Therapeutic doses of steroids must be stopped > 72 hours prior to leukapheresis. However, the following physiological replacement doses of steroids are allowed: ≤ 12 mg/m2/day hydrocortisone or equivalent.
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• Immunomodulatory drugs (e.g., IFN-gamma, anti-TNF-alpha)
• Should be stopped ≥ 2 weeks prior to leukapheresis.

• Allogeneic cellular therapy
• Must be ≥ 3 months from allogeneic stem cell transplant at the time of leukapheresis.
• Any donor lymphocyte infusions (DLI) must be completed > 4 weeks prior to leukapheresis.
• Must not have presence of grade 2 to 4 acute graft-versus-host disease (GVHD) or extensive chronic GVHD.

• GVHD therapies
• Any drug used to prevent or treat GVHD must be stopped > 2 weeks prior to leukapheresis (e.g., calcineurin inhibitors, methotrexate or other chemotherapy drugs, mycophenolate, rapamycin, thalidomide, or immunosuppressive antibodies such as anti-TNF-α, anti-IL6 or anti-IL6R). Topical steroids for localized treatment of GVHD are allowed.

• Anti T-cell Directed Therapy
• Administration of any T cell lytic or toxic agent (e.g. alemtuzumab) is strongly discouraged since residual lytic levels may destroy T-cells in the leukapheresis collection and/or prevent their in vitro CTL019 manufacturing. If such an agent has been administered within 6 weeks prior to a planned leukapheresis collection of PBMCs, contact the Sponsor, consider consultation with a pharmacology expert, and consider measuring residual drug levels, if feasible, prior to leukapheresis.

• Anti-CD19 directed therapy
• Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy unless a specific Novartis CTL019 treatment protocol would allow for prior anti-CD19 directed therapy.
• Hepatitis B or active hepatitis C (HCV RNA positive).
• Patients with an acute infection (bacterial, viral or fungal) or a positive blood culture should not undergo leukapheresis collection. A full course of anti-infective therapy must be administered before leukapheresis collection can occur to avoid contamination of the product.
• Patient should not receive long-acting growth factors or drugs used for cell mobilization (e.g., Neulasta/pegfilgrastim) within 14 days of the leukapheresis procedure. Use of short-acting growth factors (e.g. G-CSF/Neupogen/filgrastim, plerixafor) must be ≥ 5 days of leukapheresis procedure.