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

Protocol Details

Phase 1/2 Dose Escalation Study of CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults with Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000324-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 3 Years
Max Age: 35 Years

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women;
Neonates

Keywords

Philadelphia chromosome + ALL;
Lymphoma;
CD-22 Expressing Tumor;
CD-19 expressing tumor;
Adoptive Immunotherapy;
B-All;
B-precursor ALL;
Acute Lymphoblastic Leukemia;
Acute Lymphocytic Leukemia;
B-Non Hodgkin Lymphoma

Recruitment Keyword(s)

None

Condition(s)

B-NHL;
B-Non Hodgkin Lymphoma;
Acute Lymphocytic Leukemia;
Acute Lymphoblastic Leukemia;
B-precursor ALL;
B-All;
Lymphoma, Non-Hodgkin;
Leukemia, Lymphocytic, B Cell;
B-Cell Lymphoma;
B-Cell Leukemia;
Acute Lymphoid Leukemia

Investigational Drug(s)

CD19/CD22 Bicistronic CAR T cells
fudarabine

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: CD19/CD22-CAR-transduced T cells
Drug: cyclophosphamide
Drug: fludarabine

Supporting Site

National Cancer Institute

Background:

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses.

Objective:

To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL.

Eligibility:

People aged 3 to 35 with ALL or related B-cell lymphoma that has not been cured by standard therapy.

Design:

Participants will be screened. This will include:

Physical exam

Blood and urine tests

Tests of their lung and heart function

Imaging scans

Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone.

Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord.

Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells.

Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment.

Participants will be admitted to the hospital. Their own modified T cells will be returned to their body.

Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years.

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Eligibility

INCLUSION CRITERIA:

- Diagnosis

-- Participant must:

--- Have pathology confirmed B cell ALL (not isolated to the testis or CNS), CML with ALL transformation, or high-grade lymphoma (e.g., Burkitt s lymphoma, B-lymphoblastic lymphoma, diffuse large B-cell lymphoma, inclusive of low-grade lymphoma that has transformed to high grade disease); and

--- Have relapsed or been refractory after at least one standard chemotherapy regimen and at least one salvage treatment. Participants with Philadelphia chromosome + ALL must have failed prior tyrosine kinase inhibitor; and

--- Be ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have recurred after SCT; and

--- Have no evidence of graft-versus- host disease (GVHD) and have been without immunosuppressive agents for at least 30 days prior to apheresis, if undergone prior allogeneic SCT; and

--- Be unable to access (in a timely manner), ineligible for, or have relapsed/failed after or not responded to a commercially available CD19 CAR T-cell construct; and

-- Have evidence of at least minimal residual disease or PET-avid disease (lymphoma) at the time of enrollment.

- CD22/CD19 expression

-- CD19 must be detected on >15% of the malignant cells by immunohistochemistry or > 80% by flow cytometry.

-- CD22 positivity must be confirmed.

- Age >= 3 years of age and <=35 years of age at time of enrollment.

- Clinical Performance status: Participants >= 16 years of age: Karnofsky >= 50%; Participants < 16 years of age: Lansky scale >= 50%.

- Participants must have adequate organ and marrow function as defined below:

-- leukocytes >= 750/mcL*

-- platelets >= 50,000/mcL*

-- total bilirubin <=2 X ULN (except in the case of participants with documented Gilbert s disease > 3x ULN)

-- AST(SGOT)/ALT(SGPT) <=10 x institutional upper limit of normal

-- creatinine <= the maximum for age listed in the table below OR

-- measured creatinine clearance >=60 mL/min/1.73 m^2 for participants with creatinine levels above the max listed below per age.

--- Age (Years) <= 5 || Maximum Serum Creatinine (mg/dL) <= 0.8

--- Age (Years) 6 to <= 10 || Maximum Serum Creatinine (mg/dL) <= 1.0

--- Age (Years) >10 || Maximum Serum Creatinine (mg/dL) <= 1.2

*a participant will not be excluded because of pancytopenia >= Grade 3 if it is due to underlying bone marrow involvement by leukemia

- Central nervous system (CNS) Status

- Participants with leukemia with CNS 1 and 2 disease are eligible in the absence of exclusion criteria

- Participants of child-bearing or child-fathering potential must be willing to practice effective birth control from the time of enrollment until four months following lymphodepletion (LD)

- Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while on study therapy and until 1 month after the administration of CAR.

- Cardiac function: Left ventricular ejection fraction >= 45% or fractional shortening >=28%

- Pulmonary Function

-- Baseline oxygen saturation >92% on room air at rest

- Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

- Ability and willingness of participant or Legally Authorized Representative (LAR) to co- enroll on 15-C-0028: Follow-up Evaluation for Gene-Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials.

EXCLUSION CRITERIA:

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

- Participants with CNS3 disease, neurologic signs of CNS disease, radiologically detected active CNS lymphoma

- Hyperleukocytosis (>= 50,000 blasts/microL)

- Positive serum or urine beta-HCG pregnancy test performed at screening.

- Participants will be excluded based on prior therapy if they fail to meet following washout criteria:

-- Therapy: Systemic Chemotherapy, anti-neoplastic agents, antibody- based therapies

-- Washout*: >=2 weeks

-- Exceptions: 6 weeks for clofarabine or nitrosoureas; No washout for prior intrathecal chemotherapy, steroid therapy, hydroxyurea (no dose increases within prior 2 weeks) or ALL maintenance-type chemotherapy (vincristine, 6-mercaptopurine, oral methotrexate, or a tyrosine kinase inhibitor for participants with Ph+ ALL) provided there is recovery from any acute toxic effects

-- Therapy: Radiation

-- Washout*: >=3 weeks

-- Exceptions: No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the participant has measurable/evaluable disease outside the radiation window

-- Therapy: Allogeneic Stem Cell Transplant

-- Washout*: >= 100 days since SCT; >= 30 days since completion of immunosuppression; >= 6 weeks since donor lymphocyte infusion (DLI)

-- Exceptions: Cannot have evidence of active graft-versus-host disease (GVHD)

-- Therapy: CAR T-Cell Therapy or other Adoptive Cell Therapy

-- Washout*: > 30 days post infusion

-- Exceptions: For patients previously treated with CAR T-cells without interim HSCT (cohorts B1 and D1) cannot have circulating CAR T cells (or genetically modified cells) >5% by flow cytometry in peripheral blood

*Washout: Time between therapy and apheresis

- Positive HIV antibodies consistent with active HIV.

- Positive hepatitis C antibodies or positive Hepatitis B surface antigen (HbsAG) indicative of current/active HCV/HBV.

- Active second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and participant is in remission.

- 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.

- Uncontrolled, symptomatic, intercurrent 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 participant.


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Nirali N. Shah, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
10 CENTER DR
BETHESDA MD 20892
(240) 760-6970
shahnn@mail.nih.gov

NCI Pediatric Leukemia, Lymphoma Transpl
National Cancer Institute (NCI)

(240) 760-6970
ncilltct@mail.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:

NCT05442515

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

Protocol Details

Phase 1/2 Dose Escalation Study of CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults with Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000324-C

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 3 Years
Max Age: 35 Years

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women;
Neonates

Keywords

Philadelphia chromosome + ALL;
Lymphoma;
CD-22 Expressing Tumor;
CD-19 expressing tumor;
Adoptive Immunotherapy;
B-All;
B-precursor ALL;
Acute Lymphoblastic Leukemia;
Acute Lymphocytic Leukemia;
B-Non Hodgkin Lymphoma

Recruitment Keyword(s)

None

Condition(s)

B-NHL;
B-Non Hodgkin Lymphoma;
Acute Lymphocytic Leukemia;
Acute Lymphoblastic Leukemia;
B-precursor ALL;
B-All;
Lymphoma, Non-Hodgkin;
Leukemia, Lymphocytic, B Cell;
B-Cell Lymphoma;
B-Cell Leukemia;
Acute Lymphoid Leukemia

Investigational Drug(s)

CD19/CD22 Bicistronic CAR T cells
fudarabine

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: CD19/CD22-CAR-transduced T cells
Drug: cyclophosphamide
Drug: fludarabine

Supporting Site

National Cancer Institute

Background:

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses.

Objective:

To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL.

Eligibility:

People aged 3 to 35 with ALL or related B-cell lymphoma that has not been cured by standard therapy.

Design:

Participants will be screened. This will include:

Physical exam

Blood and urine tests

Tests of their lung and heart function

Imaging scans

Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone.

Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord.

Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells.

Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment.

Participants will be admitted to the hospital. Their own modified T cells will be returned to their body.

Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

- Diagnosis

-- Participant must:

--- Have pathology confirmed B cell ALL (not isolated to the testis or CNS), CML with ALL transformation, or high-grade lymphoma (e.g., Burkitt s lymphoma, B-lymphoblastic lymphoma, diffuse large B-cell lymphoma, inclusive of low-grade lymphoma that has transformed to high grade disease); and

--- Have relapsed or been refractory after at least one standard chemotherapy regimen and at least one salvage treatment. Participants with Philadelphia chromosome + ALL must have failed prior tyrosine kinase inhibitor; and

--- Be ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have recurred after SCT; and

--- Have no evidence of graft-versus- host disease (GVHD) and have been without immunosuppressive agents for at least 30 days prior to apheresis, if undergone prior allogeneic SCT; and

--- Be unable to access (in a timely manner), ineligible for, or have relapsed/failed after or not responded to a commercially available CD19 CAR T-cell construct; and

-- Have evidence of at least minimal residual disease or PET-avid disease (lymphoma) at the time of enrollment.

- CD22/CD19 expression

-- CD19 must be detected on >15% of the malignant cells by immunohistochemistry or > 80% by flow cytometry.

-- CD22 positivity must be confirmed.

- Age >= 3 years of age and <=35 years of age at time of enrollment.

- Clinical Performance status: Participants >= 16 years of age: Karnofsky >= 50%; Participants < 16 years of age: Lansky scale >= 50%.

- Participants must have adequate organ and marrow function as defined below:

-- leukocytes >= 750/mcL*

-- platelets >= 50,000/mcL*

-- total bilirubin <=2 X ULN (except in the case of participants with documented Gilbert s disease > 3x ULN)

-- AST(SGOT)/ALT(SGPT) <=10 x institutional upper limit of normal

-- creatinine <= the maximum for age listed in the table below OR

-- measured creatinine clearance >=60 mL/min/1.73 m^2 for participants with creatinine levels above the max listed below per age.

--- Age (Years) <= 5 || Maximum Serum Creatinine (mg/dL) <= 0.8

--- Age (Years) 6 to <= 10 || Maximum Serum Creatinine (mg/dL) <= 1.0

--- Age (Years) >10 || Maximum Serum Creatinine (mg/dL) <= 1.2

*a participant will not be excluded because of pancytopenia >= Grade 3 if it is due to underlying bone marrow involvement by leukemia

- Central nervous system (CNS) Status

- Participants with leukemia with CNS 1 and 2 disease are eligible in the absence of exclusion criteria

- Participants of child-bearing or child-fathering potential must be willing to practice effective birth control from the time of enrollment until four months following lymphodepletion (LD)

- Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while on study therapy and until 1 month after the administration of CAR.

- Cardiac function: Left ventricular ejection fraction >= 45% or fractional shortening >=28%

- Pulmonary Function

-- Baseline oxygen saturation >92% on room air at rest

- Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

- Ability and willingness of participant or Legally Authorized Representative (LAR) to co- enroll on 15-C-0028: Follow-up Evaluation for Gene-Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials.

EXCLUSION CRITERIA:

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

- Participants with CNS3 disease, neurologic signs of CNS disease, radiologically detected active CNS lymphoma

- Hyperleukocytosis (>= 50,000 blasts/microL)

- Positive serum or urine beta-HCG pregnancy test performed at screening.

- Participants will be excluded based on prior therapy if they fail to meet following washout criteria:

-- Therapy: Systemic Chemotherapy, anti-neoplastic agents, antibody- based therapies

-- Washout*: >=2 weeks

-- Exceptions: 6 weeks for clofarabine or nitrosoureas; No washout for prior intrathecal chemotherapy, steroid therapy, hydroxyurea (no dose increases within prior 2 weeks) or ALL maintenance-type chemotherapy (vincristine, 6-mercaptopurine, oral methotrexate, or a tyrosine kinase inhibitor for participants with Ph+ ALL) provided there is recovery from any acute toxic effects

-- Therapy: Radiation

-- Washout*: >=3 weeks

-- Exceptions: No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the participant has measurable/evaluable disease outside the radiation window

-- Therapy: Allogeneic Stem Cell Transplant

-- Washout*: >= 100 days since SCT; >= 30 days since completion of immunosuppression; >= 6 weeks since donor lymphocyte infusion (DLI)

-- Exceptions: Cannot have evidence of active graft-versus-host disease (GVHD)

-- Therapy: CAR T-Cell Therapy or other Adoptive Cell Therapy

-- Washout*: > 30 days post infusion

-- Exceptions: For patients previously treated with CAR T-cells without interim HSCT (cohorts B1 and D1) cannot have circulating CAR T cells (or genetically modified cells) >5% by flow cytometry in peripheral blood

*Washout: Time between therapy and apheresis

- Positive HIV antibodies consistent with active HIV.

- Positive hepatitis C antibodies or positive Hepatitis B surface antigen (HbsAG) indicative of current/active HCV/HBV.

- Active second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and participant is in remission.

- 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.

- Uncontrolled, symptomatic, intercurrent 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 participant.


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Nirali N. Shah, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
10 CENTER DR
BETHESDA MD 20892
(240) 760-6970
shahnn@mail.nih.gov

NCI Pediatric Leukemia, Lymphoma Transpl
National Cancer Institute (NCI)

(240) 760-6970
ncilltct@mail.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:

NCT05442515

--Back to Top--