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Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant

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ClinicalTrials.gov Identifier: NCT04815356
Recruitment Status : Not yet recruiting
First Posted : March 25, 2021
Last Update Posted : November 29, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

CAR (Chimeric Antigen Receptor) T cell therapy is a type of cancer treatment in which a person s T cells (a type of immune cell) are changed in a laboratory to recognize and attack cancer cells. Researchers want to see if this treatment can help people with hairy cell leukemia (HCL).

Objective:

To test whether it is safe to give anti-CD22 CAR T cells to people with HCL.

Eligibility:

Adults ages 18 and older with HCL (classic or variant type) who have already had, are unable to receive, or have refused other standard treatments for their cancer.

Design:

Participants will be screened with the following:

Medical history

Physical exam

Blood and urine tests

Biopsy sample

Electrocardiogram

Echocardiogram

Lung function tests

Imaging scans

Some screening tests will be repeated during the study.

Participants may need to have a catheter placed in a large vein.

Participants will have magnetic resonance imaging of the brain.

Participants will have a neurologic evaluation and fill out questionnaires.

Participants will have leukapheresis. Blood will be removed from the participant. A machine will divide whole blood into red cells, plasma, and lymphocytes. The lymphocytes will be collected. The remaining blood will be returned to the participant.

Participants will get infusions of chemotherapy drugs.

Participants will get an infusion of the anti-CD22 CAR T cells. They will stay at the hospital for 14 days. Then they will have visits twice a week for 1 month.

After treatment, participants will be followed closely for 6 months, and then less frequently for at least 5 years. Then they will have long-term follow-up for 15 years.


Condition or disease Intervention/treatment Phase
Hairy Cell Leukemia Hairy Cell Leukemia Variant Biological: CD22CART cell infusion Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant
Estimated Study Start Date : December 2, 2021
Estimated Primary Completion Date : December 1, 2036
Estimated Study Completion Date : December 1, 2036

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: Experimental therapy: Dose Escalation
Escalating doses of autologous anti-CD22-CAR T-cells in subjects to determine the MTD
Biological: CD22CART cell infusion
The treatment regimen will consist of lymphodepleting chemotherapy followed by CD22CART infusion: Days -4 to -2: fludarabine 25 mg/m2/dose Day -2: cyclophosphamide 900 mg/m2/dose Day 0: CD22CART infusion (starting at dose level 1 [DL1]: 1 x 105 transduced CAR-T cells/kg) on Day 0 Subjects will be evaluated for response at Day 28 post-CD22CART infusion.

Experimental: Experimental therapy: Dose Expansion
Autologous anti-CD22-CAR T-cells at the MTD
Biological: CD22CART cell infusion
The treatment regimen will consist of lymphodepleting chemotherapy followed by CD22CART infusion: Days -4 to -2: fludarabine 25 mg/m2/dose Day -2: cyclophosphamide 900 mg/m2/dose Day 0: CD22CART infusion (starting at dose level 1 [DL1]: 1 x 105 transduced CAR-T cells/kg) on Day 0 Subjects will be evaluated for response at Day 28 post-CD22CART infusion.




Primary Outcome Measures :
  1. safety and feasibility [ Time Frame: end of treatment ]
    Fraction of participants at each dose level who experience a toxicity along with the grades and types of toxicity and which can successfully manufacture the targeted dose number

  2. antitumor effect [ Time Frame: every year for 15 years ]
    The fraction of participants who experience a CR among the 10 evaluable participants treated at the MTD or highest safe dose


Secondary Outcome Measures :
  1. expansion and persistence [ Time Frame: every year for 5 years ]
    Measure expansion and persistence of adoptively-transferred anti-CD22-CAR-transduced T-cells in the blood and, where possible, the bone marrow

  2. MRD negative CR [ Time Frame: every year for 15 years ]
    Fraction of HCL patients who achieve MRD negative CR following treatment with anti-CD22-CAR engineered T-cells

  3. duration of response [ Time Frame: every year for 15 years ]
    The time between the initial response to therapy and subsequent disease progression or relapse

  4. progression free-survival [ Time Frame: every year for 15 years ]
    Duration of time from the start of treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first

  5. event free survival [ Time Frame: every year for 15 years ]
    Duration of time from the start of treatment until time of disease relapse, disease progression, alternative therapy given (such as radiation), or death, whichever occurs first.

  6. overall survival [ Time Frame: every year for for 15 years or until death ]
    Overall survival (OS) will be determined as the time from the start of the CD22CART infusion until death

  7. time to next treatment [ Time Frame: every year for 15 years ]
    Duration of time from the start of administration of anti-CD22-CAR engineered T-cells to next line of treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Histologically confirmed diagnosis of HCL or HCLv according to morphological and immunophenotypic criteria of WHO classification [WHO, 2008 revised 2016] of lymphoid neoplasm. Patients should have any of the following indications for therapy:

      • Absolute neutrophil count (ANC) <1/nL,
      • Hemoglobin <10g/dL,
      • Platelets<100/nL,
      • Symptomatic splenomegaly,
      • Enlarging HCL mass or bone lesion > 2cm in short axis,
      • HCL count >5/nL,
      • HCLv count doubling time <3 months,
      • Increasing lytic or blastic bone lesions

      Participants who have eligible blood counts within 4 weeks from the initiation of study will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment

    2. HCL/HCLv, after prior treatment with, ineligible for, refusal of, or inability to obtain 1) Rituximab given concurrently with or sequentially after purine analog, 2) moxetumomab pasudotox-tdft, and 3) BRAF-inhibition.
    3. CD22 expression must be detected on greater than 80% of malignant cells by flow cytometry.
    4. 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 or immunohistochemistry
    5. Age >18 years
    6. ECOG performance <2 (Karnofsky >60%), participants are exempt from this criteria if poor performance status is related to HCL
    7. Participants must have adequate organ function as defined below: Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. If participants exhibit minor lab abnormalities that are determined to be related

      to HCL (not therapy-related), then those participants will be allowed to participate

      • Total bilirubin less than or equal to 3 ULN, unless consistent with Gilbert s (ratio between total and direct bilirubin > 5)
      • AST and ALT less than or equal to 3x upper limit of normal (ULN)
      • Alkaline phosphatase < 2.5 ULN
      • Serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal calculated using eGFR or measured
      • Serum albumin > 2 g/dL
      • Prothrombin time (PT)/International Normalized Ratio < 2.5x ULN (If on warfarin, PT/INR < 3.5x ULN; If on any other anticoagulation, Prothrombin time (PT) < 2.5x ULN
      • Fibrinogen greater than or equal to 0.5x lower limit of normal
    8. Subjects with CNS disease are eligible, with exceptions
    9. Participants 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
    10. Participants of child-bearing or child-fathering potential must use effective contraception from the time of enrollment on this study and for four months after receiving the preparative regimen as agents used in this study are teratogenic.
    11. Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  1. Pregnant or breast-feeding females
  2. Systemic chemotherapy, immunotherapy, or radiation therapy less than or equal to 3 weeks prior to apheresis; with the following exception:

    • Subjects receiving steroids may be enrolled, provided there has been no increase in dose for at least 1 week prior to starting apheresis;
    • 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.
  3. Other anti-neoplastic investigational agents, or antibody based therapies currently or within 2 weeks prior to apheresis
  4. Subjects taking warfarin
  5. 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)
  6. HIV/HBV/HCV Infection:

    • 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 participants receiving combination antiretroviral therapy in the future should study results indicate effectiveness.)
    • Seropositive for hepatitis C or positive for Hepatitis B surface antigen (HbsAG). Participants who convert to negative will not be excluded for history of positive test.
  7. Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, asthma, chronic obstructive pulmonary disease, 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
  8. 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
  9. 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04815356


Contacts
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Contact: Theresa Yu, R.N. (301) 480-6195 theresa.yu@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Robert J Kreitman, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04815356    
Other Study ID Numbers: 210019
21-C-0019
First Posted: March 25, 2021    Key Record Dates
Last Update Posted: November 29, 2021
Last Verified: August 31, 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
CD-22 Expressing Tumor
Chimeric Antigen Receptor
Adoptive Immunotherapy
Additional relevant MeSH terms:
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Leukemia
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases