Trial Search Results

Autologous CD22 CAR T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies

The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from adults with relapsed/refractory B-cell malignancies (leukemia and lymphoma).

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Stanford University

Stanford Investigator(s):

Intervention(s):

  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Drug: CD22 CAR

Phase:

Phase 1

Eligibility


Inclusion Criteria:

   1. Disease Status Disease Status of ALL

      - Must have chemotherapy refractory disease defined as progression or stable
      disease after two lines of therapies, or relapsed disease after achieving CR.

      - Subjects with persistent or relapsed minimal residual disease (MRD) (by flow
      cytometry, polymerase chain reaction (PCR), Fluorescence in in situ hybridization
      (FISH), or next generation sequencing) require verification of MRD on two
      occasions at least 2 weeks apart.

      - Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia
      (Ph+ALL) are eligible if they progressed, had stable disease or relapsed after
      two lines of therapy, including tyrosine kinase inhibitors (TKIs).

      - Subjects with recurrence of isolated CNS relapse after achieving complete
      remission (CR) are eligible.

   Disease Status of aggressive B-cell NHL

      - Histologically confirmed aggressive B cell NHL including the following types
      defined by WHO 2008:

      - DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma;
      DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of
      the elderly; OR primary mediastinal (thymic) large B cell lymphoma; OR
      transformation of follicular lymphoma, marginal zone lymphoma or chronic
      lymphocytic leukemia/small lymphocytic lymphoma to DLBCL

      - Subjects with DLBCL or subjects with transformed follicular lymphoma (FL),
      marginal zone lymphoma (MZL), or chronic lymphocytic leukemia/small lymphocytic
      lymphoma (CLL/SLL) who have not received chemotherapy prior to transformation:

      - Must have received an anthracycline regimen and an anti CD20 monoclonal
      antibody (unless documented CD20-negative) and be refractory or relapsed after
      second line of DLBCL treatment. Subjects with a partial response to second line
      therapy must be ineligible for autologous transplant.

      - Subjects with transformed FL, MZL, or CLL/SLL who have received
      anthracycline-containing chemotherapy prior to transformation:

         - Must have progressed, had SD or recurred with transformed disease after
         initial treatment for DLBCL.

   2. Measureable Disease

      - Subjects with ALL: must have evaluable or measurable disease (MRD positive by
      flow cytometry, next-generation sequencing (NGS), or PCR is acceptable).

      - Subjects with aggressive B-cell NHL: must have evaluable or measurable disease
      according to the revised International Working Group (IWG) Response Criteria for
      Malignant Lymphoma[38]. Lesions that have been previously irradiated will be
      considered measurable only if progression has been documented following
      completion of radiation therapy.

   3. CD22 expression

   • Subjects with ALL: CD22 positive expression on malignant cells is required and must
   be detected by immunohistochemistry or 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 subject.

   CD22 expression must be demonstrated subsequent to any anti-CD22 targeted therapy
   (e.g. Moxetumomab pasudotox or inotuzumab ozogamicin) in subjects with ALL.

   • Subjects with aggressive B-cell NHL: CD22 expression at any level, including
   undetectable, will be acceptable. Subjects must have archival tissue available for
   analysis of CD22 expression or must be willing to undergo a biopsy of easily
   accessible disease.

   4. Prior Bone Marrow-Stem Cell Transplant Subjects who have undergone autologous stem
   cell transplant (SCT) with disease progression or relapse following SCT are eligible.
   Subjects who have undergone allogeneic SCT will be eligible if, in addition to meeting
   other eligibility criteria, they are at least 100 days post transplant, they have no
   evidence of graft versus host disease (GVHD) and have been without immunosuppressive
   agents for at least 30 days.

   5. Prior Therapy Wash-out At least 2 weeks or 5 half lives, whichever is shorter, must
   have elapsed since any prior systemic therapy at the time the subject is planned for
   leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy,
   which requires 5 half lives.

   Subjects with ALL may not have received inotuzumab ozogamicin therapy within the past
   3 months.

   Exceptions:

      1. There is no time restriction with 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. Subjects who are on standard ALL maintenance type chemotherapy (vincristine,
      6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy
      is discontinued at least 1 week or 5 half lives, whichever is shorter, prior to
      apheresis.

      4. Subjects receiving steroid therapy at physiologic replacement doses only are
      allowed provided there has been no increase in dose for at least 2 weeks 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 or the site of radiation
      has documented progression.

   6. Prior CAR Therapy Subjects who have undergone prior CAR therapy will be eligible if <
   5% of circulating levels of CD3+ cells express the previous CAR by flow cytometry; 30
   days must have elapsed post CAR infusion prior to apheresis.

   7. Toxicities due to prior therapy must be stable or resolved (except for clinically non
   significant toxicities such as alopecia or cytopenias

   8. Age greater than or equal to 18 years of age

   9. Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2; or
   Karnofsky ≥ 60%

10. Normal Organ and Marrow Function (supportive care is allowed per institutional
   standards, i.e. filgrastim, transfusion)

      - Absolute neutrophil count (ANC) ≥ 750/uL*

      - Platelet count ≥ 50,000/uL*

      - Absolute lymphocyte count (ALC) ≥ 150/uL*

   Adequate renal, hepatic, pulmonary and cardiac function defined as:

      - Creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by Cockcroft Gault
      Equation) ≥ 60 mL/min

      - Serum alanine or aspartate aminotransferase (ALT/AST) ≤ 10x Upper limit of normal
      (ULN) (Elevated ALT/AST related to leukemia involvement of the liver will not
      disqualify a subject).

      - Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert's syndrome.

      - Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant
      pericardial effusion as determined by an echocardiogram (ECHO), multigated
      radionuclide angiography (MUGA) or Cardiac MRI [performed within 180 days or
      after most recent anthracycline based treatment or mediastinal radiation therapy
      (whichever is most recent)]

      - No clinically significant ECG findings

      - No clinically significant pleural effusion

      - Baseline O2 saturation > 92% on room air * A subject will not be excluded because
      of pancytopenia ≥ Grade 3 if it is felt by the investigator to be due to
      underlying leukemia/lymphoma.

11. CNS Status Subjects with CNS involvement are eligible as long as there are no overt
   signs or symptoms that in the evaluation of the investigator would mask or interfere
   with the neurological assessment of toxicity.

12. Females of childbearing potential must have a negative serum or urine pregnancy test
   (females who have undergone surgical sterilization or who have been postmenopausal for
   at least 2 years are not considered to be of childbearing potential)

13. Contraception Subjects 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 (4)
   months after receiving the preparative lymphodepletion regimen.

14. Ability to give informed consent. Must be able to give informed consent. Legal
   authorized representative (LAR) is permitted if subject is cognitively able to provide
   verbal assent.

Exclusion Criteria:

   1. Recurrent or refractory ALL limited to isolated testicular disease.

   2. Hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the
   estimation of the investigator and sponsor would compromise ability to complete study
   therapy.

   3. History of other malignancy, unless disease free for at least 3 years. At the
   discretion of the Principal Investigator, subjects in remission for 1-2 years prior to
   enrollment may be deemed eligible after considering the nature of other malignancy,
   likelihood of recurrence during one year following CAR therapy, and impact of prior
   treatment on risk of CD22-CAR T cells. Subjects in remission <1 year are not eligible.

      - Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder,
      breast) is eligible.

      - Hormonal therapy in subjects in remission > 1 year will be allowed.

   4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple
   urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if
   responding to active treatment.

   5. Ongoing infection with :

      - HIV,

      - Hepatitis B (HBsAg positive) or

      - Hepatitis C virus (HCV) (anti HCV positive). A history of hepatitis B or
      hepatitis C is permitted if the viral load is undetectable per quantitative PCR
      and/or nucleic acid testing.

   6. CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar
   disease, or any autoimmune disease with CNS involvement that in the judgment of the
   investigator may impair the ability to evaluate neurotoxicity.

   7. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
   other clinically significant cardiac disease within 12 months of enrollment.

   8. Any medical condition that in the judgement of the sponsor investigator is likely to
   interfere with assessment of safety or efficacy of study treatment.

   9. History of severe immediate hypersensitivity reaction to any of the agents used in
   this study.

10. Women who are pregnant or breastfeeding.

11. In the investigators judgment, the subject is unlikely to complete all protocol
   required study visits or procedures, including follow up visits, or comply with the
   study requirements for participation.

12. Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid
   arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease
   modifying agents within the last 2 years.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Juliana Craig
650-736-0912
Recruiting