NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

21-C-0019

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women;
Fetuses;
Children

Keywords

CD-22 Expressing Tumor;
Chimeric Antigen Receptor;
Adoptive Immunotherapy

Recruitment Keyword(s)

None

Condition(s)

Hairy Cell Leukemia;
Hairy Cell Leukemia Variant

Investigational Drug(s)

T cells modified using the lentiviral vector containing the Anti-CD22 CAR gene
cyclophosphamide

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: CD22CART cell infusion

Supporting Site

National Cancer Institute

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.

--Back to Top--

Eligibility

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. Participants 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. Participants 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 criterion 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 as noted in the exclusion criteria

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 2 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. (Participants 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)


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Robert J. Kreitman, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CLINICAL CENTER BG RM 13N248A
10 CENTER DR
BETHESDA MD 20892
(301) 480-6187
kreitmar@mail.nih.gov

Olena Sierra Ortiz
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 13N254
10 Center Drive
Bethesda, Maryland 20892
(240) 858-3185
olena.sierraortiz@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT04815356

--Back to Top--