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.

   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 1 year of age (and at least 15 kg) and less than or equal to
   30 years of age at time of enrollment. NOTE: The first 3 patients in the first dose
   cohort must be greater than or equal to 16 years of age, while the first 2 patients in
   subsequent dose cohorts must be greater than or equal to 16 years of age.

   5. Subjects with the following CNS status are eligible:

      - CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin
      preparation, regardless of the number of WBCs;

      - CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for
      blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:

         - CNS 2a: < 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;

         - CNS 2b: greater than or equal to 10/uL RBCs; < 5/uL WBCs and cytospin
         positive for blasts;

         - CNS 2c: greater than or equal to 10/uL RBCs; greater than or equal to 5/uL
         WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer
         algorithm.

   6. CNS3 who has failed salvage systemic and intensive IT chemotherapy (and therefore not
   eligible for radiation)

   7. Patients with isolated CNS relapse will be eligible if they have previously been
   treated with cranial radiation (at least 1800 cGy) but only in the absence of
   neurologic symptoms suggestive of bulky CNS disease, such as cranial nerve palsy due

   to active disease.

   8. 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.

   9. 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.

10. 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.

11. Females of child-bearing potential must have a negative pregnancy test because of the
   potentially dangerous/unknown effects on the fetus.

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

12. 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.

13. 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%.

EXCLUSION CRITERIA

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

   1. Recurrent or refractory ALL limited to isolated testicular or isolated central nervous
   system (CNS) disease.

   2. Hepatic function: Inadequate liver function defined as total bilirubin > 2 x upper
   limit of normal (ULN) (except in the case of subjects with documented Gilbert s
   disease > 3 x ULN) or transaminase (ALT and AST) > 5 x ULN based on age- and
   laboratory specific normal ranges;

   3. Renal function: Greater than age-adjusted normal serum creatinine or a creatinine
   clearance < 60 mL/min/1.73 m^2.

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

      - Less than 5 years old, less than or equal to 10 years old, maximum serum
      creatinine:1.0 mg/dL

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

   4. Hematologic function:

      - Absolute neutrophil count (ANC) < 750/uL, or platelet count < 50,000/uL, if these
      cytopenias are not judged by the investigator to be due to underlying disease
      (i.e. potentially reversible with anti-neoplastic therapy);

      - A subject will not be excluded because of pancytopenia greater than or equal to
      Grade 3 if it is due to disease, based on the results of bone marrow studies.

   5. Subjects with radiologically-detected CNS lymphoma

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

   7. Pregnant or breast-feeding females;

   8. Recent prior therapy:

   9. 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 or 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.

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

         5. For radiation therapy: Radiation therapy must have been completed at least 3
         weeks prior to enrollment, 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.

            - Other anti-neoplastic investigational agents currently or within 2
            weeks prior to apheresis (i.e. start of protocol therapy);

            - 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.

            - 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).

            - Prior antineoplastic antibody therapy within 5 half-lives or 1 week
            prior to apheresis, whichever is greater.

10. 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
      be undertaken 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).

11. 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;

12. 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;

13. 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)

14. Severely impaired lung function defined as spirometry and DLCO that is 50% of the
   normal predicted value corrected for hemoglobin and alveolar volume and/or oxygen
   saturation that is 92% or less on room air while at rest. For patients who do not have
   respiratory symptoms (e.g. dyspnea at rest, known requirement for supplemental oxygen
   therapy), pulmonary function tests are not required.

   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.

15. Active macrophage activation syndrome (MAS) as evidenced by laboratory abnormalities
   (e.g. elevated ferritin,, elevated triglycerides), hemophagocytosis on the bone marrow
   sample, and/or clinical indications.

Ages Eligible for Study

1 Year - 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