Know Cancer

or
forgot password

A Phase I Dose Escalation Trial Using In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the B-Cell Specific Antigen CD19 Positive Residual Or Relapsed Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Progenitor Cell Transplantation


Phase 1
N/A
19 Years
Open (Enrolling)
Both
Acute Lymphocytic Leukemia

Thank you

Trial Information

A Phase I Dose Escalation Trial Using In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the B-Cell Specific Antigen CD19 Positive Residual Or Relapsed Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Progenitor Cell Transplantation


Inclusion Criteria:



- Patients treated on this protocol will have been diagnosed with CD19+ leukemia at
less than 19 years of age.

- History of CD19+ leukemia with evidence of bone marrow relapse or persistent MRD
following allogenic hematopoietic stem cell transplantation.

- Persistent minimal residual disease after transplantation must be demonstrated by
morphology, karyotype, FSH, flow cytometry or RT-PCR with at least 2 sequential
testings separated by at least 1 week.

- We expect that there will be cases in which a patient will experience a leukemia
relapse and will require chemotherapy during the establishment, expansion and
modification of EBV-CTLs. The timeline for establishing the EBV-BLCL (3-5 weeks),
establishing EBV specific T-cell line (6-8 weeks) and expanding the genetically
modified EBV specific T-cell line (1-4 weeks) is considerable. During this time
patients may receive chemotherapy at the discretion of their treating physician. If
the patient receives chemotherapy they must have recovered from any chemotherapy
induced toxicity and meet all eligibility criteria for organ function for this
protocol at the time the conditioning therapy is initiated. If the patient has been
rendered hypoplastic by the chemotherapy, the patient may proceed to T-cell therapy
with conditioning therapy prior to the resurgence of a blastic marrow.

- The patient's hematopoietic stem cell transplant donor must consent to a
leukapheresis or whole blood donations obtained at one or more phlebotomies which, in
aggregate, will total approximately 250 ml for adults and no more than 5ml/kg per
draw from pediatric donors. Related donors under the age of 18 will donate peripheral
blood collected by phlebotomy (including a unit of blood if weight permits) and shall
not undergo leukopheresis which is considered above minimal risk to the donor.

- Unrelated volunteer donors should be between the age if 18 and 60 years as these are
the age restrictions for volunteer unrelated donor registries. There is no upper age
limit for a related donor. However, the minimum age for a related donor is 7 years as
this is the youngest age a person can be considered capable of giving assent to
participate in a research study.

- Organ Function as determined on the day of initiation of lymphodepleting
cytoreduction.

1. KPS or Lansky score > 30

2. Renal function at the time of treatment: Creatinine ≤2.0mg/dL

3. Hepatic function at time of treatment: AST ≤ 3.0 x the institutional ULN, total
bilirubin ≤ 2.5 x the institutional ULN

4. Pulmonary function: Oxygen saturation ≥ 90% on room air

- Patients treated on this protocol will have been diagnosed with CD19+ leukemia at
less than 19 years of age.

- Patients with CNS relapse are eligible. However, if patient receives intrathecal
chemotherapy, at least 24 hours must elapse prior to the T-cell infusion.

Exclusion Criteria:

- Patients with active (grade 2-4) acute graft versus host disease (GVHD), chronic GVHD
or an overt autoimmune disease (e.g. hemolytic anemia) requiring glucocorticosteroid
treatment (>0.5 mg/kg/day prednisone or its equivalent) as treatment.

- Patients with other life-threatening conditions not related to leukemia (e.g.
veno-occlusive disease or uncontrolled bacterial, viral or invasive fungal infection)
which would confound evaluation of the effects of an infusion of genetically modified
T-cells.

- Females who are pregnant.

- Patient or guardian is unable to give informed consent or unable to comply with the
treatment protocol including appropriate supportive care, follow-up, and research
tests.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluate the safety/persistence of escalating doses of allogeneic EBV specific CTL modified to express artificial T cell receptors targeting CD19 molecule given for persistence or relapse of B-Cell ALL post allogeneic HSCT.

Outcome Time Frame:

3 years

Safety Issue:

Yes

Principal Investigator

Nancy Kernan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

11-038

NCT ID:

NCT01430390

Start Date:

September 2011

Completion Date:

September 2014

Related Keywords:

  • Acute Lymphocytic Leukemia
  • In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic
  • T-Lymphocytes (EBV-CTLs)
  • CD19 specific T-cells
  • 11-038
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Memorial Sloan-Kettering Cancer Center 1275 York AvenueNew York, New York  10021