Trial Search Results

Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies

Background:

- One type of cancer therapy takes blood cells from a person, changes them in a lab, then gives the cells back to the person. In this study, researchers are using an anti-CD22 gene, a virus, and an immune receptor to change the cells.

Objective:

- To see if giving anti-CD22 Chimeric Antigen Receptor (CAR) cells to young people with certain cancers is safe and effective.

Eligibility:

- People ages 1-30 with a leukemia or lymphoma that has not been cured by standard therapy.

Design:

- Participants will be screened to ensure their cancer cells express the CD22 protein. They will also have medical history, physical exam, blood and urine tests, heart tests, scans, and x-rays. They may give spinal fluid or have bone marrow tests.

- Participants may have eye and neurologic exams.

- Participants will get a central venous catheter or a catheter in a large vein.

- Participants will have white blood cells removed. Blood is removed through a needle in an arm. White blood cells are removed. The rest of the blood is returned by needle in the other arm.

- The cells will be changed in a laboratory.

- Participants will get two IV chemotherapy drugs over 4 days. Some will stay in the hospital for this.

- All participants will be in the hospital to get anti-CD22 CAR cells through IV. They will stay until any bad side effects are gone.

- Participants will have many blood tests. They may repeat some screening exams.

- Participants will have monthly visits for 2-3 months, then every 3-6 months. They may repeat some screening exams.

- Participants will have follow-up for 15 years.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Biological: CD22-CAR

Phase:

Phase 1

Eligibility


- INCLUSION CRITERIA:

      1. Patient must have a B cell ALL (inclusive of ALL blast transformation from CML)
      or lymphoma and must have relapsed or refractory disease after at least one
      standard chemotherapy regimen and one salvage regimen. In view of the PI and the
      primary oncologist, there must be no available alternative curative therapies and
      subjects must be either ineligible for allogeneic stem cell transplant (SCT),
      have refused SCT, recurred after SCT, or have disease activity that prohibits SCT
      at the time of enrollment.

      2. CD22 expression must be detected on greater than 15% of the malignant cells by
      immunohistochemistry or greater than 80% by flow cytometry. The choice of whether
      to use flow cytometry or immunohistochemistry will be determined by what is the
      most easily available tissue sample in each patent. In general,
      immunohistochemistry will be used for lymph node biopsies, flow cytometry will be
      used for peripheral blood and bone marrow samples and CSF when feasible.

      3. Patients must have measurable or evaluable disease at the time of enrollment,
      which may include any evidence of disease including minimal residual disease
      detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR)
      analysis.

      4. Greater than or equal to 3 years of age (and at least 14.5 kg) and less than or
      equal to 30 years of age at time of enrollment.

      5. Subjects with CNS disease are eligible, with exceptions as noted in the exclusion
      criteria

      6. Patients, parents/guardian(s), legally authorized representative (LAR), or
      durable power of attorney must be able to give consent and sign the informed
      consent document. Pediatric subjects will be included in age appropriate
      discussion and verbal assent will be obtained for those > 7 years of age, when
      appropriate.

      7. Clinical performance status: Patients greater than or equal to 16 years of age:
      Karnofsky greater than or equal to 50%; Patients < 16 years of age: Lansky scale
      greater than or equal to 50%. Subjects who are unable to walk because of
      paralysis, but who are upright in a wheelchair will be considered ambulatory for
      the purpose of calculating the performance score.

      8. Patients of child-bearing or child-fathering potential must be willing to
      practice birth control from the time of enrollment on this study and for four
      months after receiving the preparative regimen.

      9. Patients must have adequate organ function as described below:

   10. Cardiac function: Left ventricular ejection fraction greater than or equal to 45%
      or fractional shortening greater than or equal to 28%.

   11. Pulmonary function: Patients without respiratory symptoms (e.g. dyspnea at rest,
      known requirement for supplemental oxygen therapy) and who have an oxygen
      saturation greater than or equal to 92% on room air, will be eligible. For
      patients not meeting this criteria, pulmonary function tests will be performed to
      confirm that the DLCO/VA/Adj is 50% of the normal predicted value corrected for
      hemoglobin and alveolar volume in order to meet eligibility.(For children who are
      unable to cooperate for PFTs, the criterion is: No evidence of dyspnea at rest,
      no exercise intolerance and no requirement for supplemental oxygen therapy. )

   12. Hematologic function:

         - Absolute neutrophil count greater than or equal to 750/mcL

         - Platelets greater than or equal to 50,000/mcl

         - A subject will not be excluded because of pancytopenia related to disease

   13. Liver Function:

      --AST (SGOT)/ALT (SGPT): less than or equal to 20 x institutional upper limit of
      normal

      --Total bilirubin less than or equal to 2 x ULN (ecept in the case of subjects
      with documented Gilbert s disease greater than or equal to 3 x ULN)

   14. Renal Function: Normal creatinineCreatinine level < the maximum for age listed in
      the table below OR creatinine clearance greater than or equal to 60 mL/min/1.73
      m2 for patients with creatinine levels above institutional normal.

         - less than or equal to 5 years old: maximum serum creatinine 0.8mg/dL

         - between 6 and 10 years old: maximum serum creatinine 1.0mg/dL

         - greater than 10 years old: maximum serum creatinine 1.2mg/dL

   14. Patients with history of allogeneic stem cell transplantation are eligible if at
   least 100 days post-transplant, if there is no evidence of active GVHD and no longer
   taking immunosuppressive agents for at least 30 days prior to enrollment.

   15. Patients previously treated with anti-CD19 CAR or other adoptive cell therapies
   will be eligible if all other eligibility criteria are met but will be evaluated as a
   separate strata from CAR-naive patients in the expansion phase. Circulating CAR T
   cells must be <5% in peripheral blood.

EXCLUSION CRITERIA:

Subjects meeting any of the following criteria are not eligible for participation in the
study:

1. Subjects with radiologically-detected active CNS lymphoma, leptomeningeal CNS disease or
isolated CNS disease which are eligible for definitive CNS directed radiationtherapy will
be excluded.

2 .Hyperleukocytosis (greater than or equal to 50,000 blasts/ L) or rapidly progressive
disease that in theestimation of the investigator and sponsor would compromise ability to
complete study therapy;

3. Pregnant or breast-feeding females

4. Recent prior therapy:

5. Systemic chemotherapy less than or equal to 2 weeks (6 weeks for clofarabine or
nitrosoureas) or radiation therapy less than or equal to 3 weeks prior to apheresis;

Exceptions:

   1. There is no time restriction in regard to prior intrathecal chemotherapy provided
   there is complete recovery from any acute toxic effects of such;

   2. Subjects receiving hydroxyurea may be enrolled provided there has been no increase in
   dose for at least 2 weeks prior to starting apheresis

   3. Patients who are on standard ALL maintenance type chemotherapy (vincristine, 6-
   mercaptopurine, oral methotrexate, or a tyrosine kinase inhibitor for patients with
   Ph+ ALL) may be enrolled provided that chemotherapy is discontinued at least 1

week prior to apheresis.

d. Subjects receiving steroids may be enrolled, provided there has been no increase in dose
for at least 1 week prior to starting apheresis;

e. For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior
to enrollment (including CNS radiation), with the exception that there is no time
restriction if the volume of bone marrow treated is less than 10% and also the subject has
measurable/evaluable disease outside the radiation port.

6. Other anti-neoplastic investigational agents, or antibody based therapies currently or
within 2 weeks prior to apheresis;

7. Subjects must have recovered from the acute side effects of their prior therapy, such
that eligibility criteria are met. Cytopenias deemed to be disease-related and not
therapy-related are exempt from this exclusion.

8. Prior CAR therapy within 30 days prior to apheresis or prior CAR therapy at any time
with evidence for persistence of CAR T cells in blood samples (circulating levels of
genetically modified cells of greater than or equal to 5% by flow cytometry).

9. HIV/HBV/HCV Infection:

   1. Seropositive for HIV antibody. (Patients with HIV are at increased risk of lethal
   infections when treated with marrow-suppressive therapy. Appropriate studies will
   beundertaken in patients receiving combination antiretroviral therapy in the future
   should study results indicate effectiveness.)

   2. Seropositive for hepatitis C or positive for Hepatitis B surface antigen (HbsAG).

   10. Uncontrolled, symptomatic, intercurrent illness including but not limited to
   infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia,
   psychiatric illness, or social situations that would limit compliance with study
   requirements or in the opinion of the PI would pose an unacceptable risk to the
   subject;

   11. Second malignancy other than in situ carcinoma of the cervix, unless the tumor was
   treated with curative intent at least two years previously and subject is in
   remission;

   12. History of severe, immediate hypersensitivity reaction attributed to compounds of
   similar chemical or biologic composition to any agents used in study or in the
   manufacturing of the cells (i.e. gentamicin);

Ages Eligible for Study

3 Years - 30 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Recruiting