Principal Investigator: Michael Boyer
Keywords: Apheresis , CD19 Expressing Malignancies , Pediatric , Oncology Department: Hematology
IRB Number: 00076653 Co Investigator:  
Specialty: Pediatric Hematology and Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Diana Hernandez

Brief Summary

Primary Objective

The primary objective of this study is the collection of PBMCs for potential utilization in a CTL019 research protocol via standardized procedures for leukapheresis, cryopreservation (if required), and storage (if required).

Inclusion Criteria

1. Signed written informed consent, or signed parental permission form and assent form (as applicable), must be obtained prior to any study procedures

2. retired from protocol version 02

3. CD19 expressing malignancy for which a CTL019 treatment protocol is currently enrolling or under IRB/EC review

4. 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

5. Platelet count ≥ 50,000/microliter at screening. Transfusion support can be provided within 24 hours of starting the leukapheresis procedure to meet this criterion

6. 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

7. Peripheral blood absolute lymphocyte count (ALC) ≥ 500/microliter at screening or if ALC <500/μL, then the absolute CD3 lymphocyte count must be ≥150/μL at screening

8. For patients who have undergone allogeneic transplant, must be ≥ 3 months from allogeneic SCT at the time of leukapheresis

9. 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

1. 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

2. (Retired from protocol version 04) Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at screening

3. Human Immunodeficiency Virus (HIV) infection at screening

4. (Retired from protocol version 01)

5. Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) at screening

6. 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

7. Treatment with any prior gene therapy product

8. Patient has participated in a research study using an investigational agent within the last 30 days prior to screening

9.(Retired from protocol version 04) Patient has received growth factors or drugs used for cell mobilization (e.g. filgrastim, peg-filgrastim, plerixafor, other drugs) within 14 days of the apheresis procedure  leukapheresis 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

10. retired from Protocol 01

11. The following treatments/medications are excluded:

  • Chemotherapy:
    • Cytotoxic chemotherapy drugs must not be given within 2-4 weeks of apheresis
    • 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- sparaginase must be stopped >4 weeks prior to leukapheresis
    • Low dose daily or weekly maintenance chemotherapy should be stopped ≥ 2 weeks prior to apheresis 
    • Pegylated-asparaginase must be stopped >4 weeks prior to leukapheresis
  • 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
  • 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 > 24 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 planned leukapheresis collection of PBMC, contact the Sponsor, consider consultation with an pharmacology expert, and consider measuring residual drug levels, if feasible, prior to leukapheresis.

12. Hepatitis B (see Appendix 1 for interpretation of Hepatitis B results) or active hepatitis C (HCV RNA positive)

13. 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.
14. 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 shortacting growth factors (e.g. G-CSF/Neupogen/filgrastim, plerixafor) must be ≥ 5 days of leukapheresis procedure.