This study is NOT currently recruiting participants.
Number
001783-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Neonates;Pregnant Women
Keywords
Lymphoma; CD-22 Expressing Tumor; Chimeric Antigen Receptor; Adoptive Immunotherapy; CAR T-cell Therapy; Cellular Immunotherapy; CRG-022; CD22
Recruitment Keyword(s)
None
Condition(s)
Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Investigational Drug(s)
Cyclophosphamide Fludarabine Phosphate
Investigational Device(s)
Intervention(s)
Drug: Fludarabine Drug: Cyclophosphamide Biological/Vaccine: CRG-022
Supporting Site
National Cancer Institute
Large B-cell lymphomas (LBCLs) are an aggressive type of blood cancer. A treatment called chimeric antigen receptor T-cell therapy (CAR T-cell therapy) has helped many people with LBCLs live longer. CAR T-cell therapy uses a person s own T cells, a type of white blood cell, that have been modified to target a protein called CD19 on cancer cells. The modified T cells kill the cancer cells. But LBCLs return after treatment in up to 50% of people.
Objective:
To test a new type of CAR T-cell therapy (CRG-022) in people with LBCLs. CRG-022 targets a different tumor protein (CD22).
Eligibility: People aged 18 years or older with LBCL. The LBCL must have failed to respond or returned after treatment with CD19-directed CAR T-cell therapy.
Design:
Participants will undergo leukapheresis: Blood is removed from the body through a tube attached to a needle inserted into a vein. The blood passes through a machine that separates out the white blood cells. The remaining blood is returned to the body through a second needle. The T cells will be separated out; they will be sent to a lab to be genetically modified.
Participants will take drugs for 5 days to prepare for the CAR T-cell therapy. Then they will receive their modified T cells through a needle inserted into a vein. They will stay in the hospital for at least 7 days after the treatment.
Participants will have 25 follow-up visits for the first 2 years after treatment. They will have biannual, then annual, visits for up to 15 years.
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Inclusion Criteria Patients are eligible to be included in the study only if they meet all of the following criteria: - Patients must provide signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. - Patients must be >= 18 years of age at the time of signing the informed consent. - Patients must have LBCL histologically confirmed by the local pathology laboratory, including one of the following types defined by the 2022 WHO Classification of Lymphoid Neoplasms. A central review of pathology is not required prior to study enrollment. a. Diffuse LBCL (DLBCL) not otherwise specified (NOS), including germinal center B-cell (GCB) type or active B-cell (ABC) type b. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma) c. High-grade B-cell lymphoma, NOS d. DLBCL arising from follicular lymphoma (FL; transformed follicular lymphoma) e. DLBCL arising from marginal zone lymphoma (MZL; transformed marginal zone lymphoma) f. Primary mediastinal large B-cell lymphoma (PMBL) g. FL, Grade 3B/follicular large B-cell lymphoma (FLBL) - Patients must have relapsed or refractory disease after the last therapy defined as follows: a. Progressive disease (PD)/stable disease (SD) after the last therapy OR b. Relapsed disease following a CR or progressive disease following a partial response (PR) after the last therapy. - Patients must have at least one radiographically measurable lesion according to Lugano criteria. a. Radiographically measurable disease is defined as at least 1 bi-dimensionally measurable nodal lesion of > 1.5 cm in its longest dimension, or at least 1 bi-dimensionally measurable extra nodal lesion of > 1.0 cm in its longest dimension. b. Lesions that were previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. - Patients must have a washout period of at least 2 weeks or 5 half-lives, whichever is shorter, since any prior cancer therapy, at the time the patient undergoes leukapheresis, except as follows: a. Prior bendamustine: a minimum of 6 months must have elapsed from the last infusion of bendamustine to enrollment in the current study. b. Prior CD19-directed CAR T-cell therapy: a minimum of 30 days must have elapsed between the CD19-directed CAR T-cell infusion and enrollment to the current study. c. Prior bispecific T-cell engaging antibody therapy: a minimum of 30 days must have elapsed between the last dose of bispecific T-cell engaging antibody therapy and enrollment to the current study. d. Autologous stem cell transplant: a minimum of 6 weeks must have elapsed from the stem cell infusion to enrollment to the current study. e. Central nervous system (CNS) prophylaxis (eg, intrathecal methotrexate): must be stopped at least 1 week prior to enrollment on the current study. f. Prior corticosteroids: a minimum of 7 days prior to leukapheresis. - Patients must have a tumor tissue biopsy sample following the most recent therapy available for central pathology evaluation; results of this evaluation do not need to be available prior to enrollment. A formalin-fixed paraffin-embedded tissue block, unstained slides, or a fresh biopsy provided in neutral buffered formalin, along with a corresponding local pathology report indicating CD19, CD20, and CD22 expression is required for submission to the Sponsor s central pathology laboratory. a. Brushings, cell pellets from effusions or ascites and lavage, and previously stained slides are not acceptable. b. Archival tissue from prior biopsies may also be submitted to the Sponsor central pathology lab in addition to the required biopsy material. - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. - Patients must have adequate hematologic and end-organ function, defined as follows: a. Absolute neutrophil count (ANC) >= 1000/microL b. Platelet count >= 75,000/microL or >= 50,000/microL in patients with known presence of marrow disease. c. Absolute lymphocyte count (ALC) >= 100/microL. d. Estimated creatinine clearance >= 45 mL/minute by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) method or on the basis of 24-hour urine collection, or other institutional standard methods. e. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <= 2.5 times the institutional upper limit of normal (ULN). f. Total bilirubin <= 1.5 mg/dL (except in patients with Gilbert syndrome). g. Cardiac left ventricular ejection fraction (LVEF) >= 45% and no evidence of pericardial effusion. h. Blood oxygen saturation (SaO2) > 92% on room air. i. Serum albumin >= 2.5 g/dL. - Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after conditioning chemotherapy or CRG-022. Woman must agree to refrain from donating eggs during the same period. a. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. b. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. c. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception. d. Women of childbearing potential must have a negative pregnancy test result within 7 days prior to leukapheresis. Women who are considered not to be of childbearing potential are not required to have a pregnancy test. - Men must agree to be abstinent (refrain from heterosexual intercourse) or use a condom with spermicide in combination with a highly effective method of contraception by a partner and agreement to not donate sperm. a. With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom with spermicide during the treatment period and for at least 12 months after the last dose of conditioning chemotherapy of CRG-022. Men must refrain from donating sperm during this same period. b. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure. c. A condom is required to be used also by vasectomized men, as well as during intercourse with a male partner, in order to prevent delivery of the drug via seminal fluid. d. Male patients considering preservation of fertility should bank sperm before study treatment. - Patients must be, in the Investigator s judgment, able and willing to comply with the study protocol. - Patients must be willing and able to remain within 1 hour of the treating center for at least 4 weeks after infusion. - Patients must be stable or have recovered from non-hematologic toxicities due to prior therapy to Grade <= 1 (except for clinically non significant toxicities such as alopecia). Exclusion Criteria Patients are excluded from the study if any of the following criteria apply: - Patients who have a history of malignancy other than the lymphoma under investigation in this study, except that patients with the following malignancies/treatment characteristics are eligible: a. Patients with a history of malignancy that has been treated with curative intent at least 2 years prior to screening and with no evidence of relapse if no concurrent anti-cancer therapy (except hormonal therapy) is being given. b. Patients with a history of malignancy with a negligible risk of metastasis or death (eg, 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer. c. Patients who have prostate cancer with no evidence of metastatic disease and are not on active therapy, except anti-androgen therapy. - Patients with active fungal, bacterial, viral, or other infection. Prophylactic antimicrobials are allowed. - Patients who received prior allogeneic stem cell, organ transplant, or allogeneic CAR therapy. - Patients who received prior anti-CD52 antibody therapy. - Patients with history of CNS involvement of lymphoma within 1 year prior to enrollment. - Patients with ongoing cardiac involvement of lymphoma. - Patients with a history of CD22-directed therapy for lymphoma. - Patients with a history of infection with any of the following: human immunodeficiency virus (HIV); hepatitis B virus (HBV), as determined by positivity for hepatitis B serum antigen (HbsAg) or hepatitis B core antibody (HbcAb); or hepatitis C virus (HCV), as determined by positivity for anti-HCV antibody. a. A patient with a history of infection with HBV or HCV may enroll if viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing. - Patients with significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including the following: a. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, serious cardiac arrhythmia or other clinically significant cardiac disease within 12 months prior to enrollment. b. Active pulmonary disease (such as severe obstructive pulmonary disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis). History of limited radiation pneumonitis is allowed. c. Clinically significant liver disease, including cirrhosis. d. Clinically significant neurological disease (such as cerebrovascular ischemia/hemorrhage, dementia, seizure disorder, or cerebellar disease). - Patients with a history of autoimmune disease resulting in significant end-organ disease or requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years. a. Physiologic dose of steroid (prednisone <= 7.5 mg/day or equivalent) is acceptable. b. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. c. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. d. Patients with history of immune thrombocytopenic purpura or autoimmune hemolytic anemia not requiring active treatment may be eligible. - Patients with evidence of moderate to severe forms of primary immunodeficiencies. - Patients with a history of severe, immediate hypersensitivity reaction attributed to aminoglycosides or any of the agents used in this study (eg, dimethyl sulfoxide [DMSO], tocilizumab). - For women: pregnant or breastfeeding. - Patients who underwent recent major surgery (within 4 weeks prior to leukapheresis), other than for diagnosis. - Patients with any in-dwelling line or drain (eg, percutaneous nephrostomy tube, in dwelling Foley catheter, biliary drain). Dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted. - Patients with a history of symptomatic deep vein thrombosis or pulmonary embolism requiring anticoagulation therapy within 6 months prior to enrollment. - Patients who received treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or are anticipated to need such a vaccine during the post-treatment period (ie, up to 24 months post-infusion). - Patients with Richter s transformation of chronic lymphatic leukemia (CLL). - Patients with T-cell/histiocyte-rich large B-cell lymphoma. Patients with Burkitt lymphoma. - Patients who require urgent therapy due to mass effects of tumor of impending oncologic emergency (eg, bowel obstruction, major blood vessel compression or tumor lysis syndrome). - Patients with any other significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results. - Patients who, in the Investigator s judgment, are unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. - Patients being treated concurrently with any other investigational agent, except for the investigational product under study (ie, CRG-022). Examples of other investigational products that would be exclusionary include supportive care agents like investigational antifungals. - Patients who require growth factor support or platelet transfusion within the past 7 days to satisfy ANC or platelet count eligibility criteria. Cohort-Specific Criteria Cohort 1 (CD19-CAR T-Cell Therapy Exposed/T-Cell Engager Naive): - Prior treatment with a CD19-directed CAR T-cell therapy. Commercially approved and experimental autologous CD19-directed CAR T-cell products are acceptable. - No prior exposure to bispecific T-cell engaging antibody therapy (eg, mosunetuzumab, glofitamab, epcoritamab, etc). Cohort 2 (Out of Specification): - Patients eligible for any cohort in which the product is out of specification and deemed safe to administer. Cohort 3 (CD19-CAR T-Cell Therapy Exposed/T-Cell Engager Exposed): - Prior treatment with a CD19-directed CAR T-cell therapy. Commercially approved and experimental autologous CD19-directed CAR T-cell products are acceptable. - Prior treatment with bispecific T-cell engaging antibody therapy (eg, mosunetuzumab, glofitamab, epcoritamab, etc). Cohort 4 (CAR T-Cell Therapy Naive): - No prior treatment with a CAR T-cell therapy including approved and experimental autologous CAR T-cell products. - No more than 2 prior lines of therapy -- Patients must have received at least 1 prior chemoimmunotherapy (CIT) containing regimen (ie, regimen must contain a CD20 targeted therapy plus an anthracycline). -- Patients can be primary refractory to prior CIT or relapsed after PR or CR. -- Prior bispecific T-cell engaging antibody therapy (eg, mosunetuzumab, glofitamab, epcoritamab, etc) containing regimens are allowed, however at least 30 days must have passed from the last dose to the time of leukapheresis.
Patients are eligible to be included in the study only if they meet all of the following criteria:
- Patients must provide signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Patients must be >= 18 years of age at the time of signing the informed consent.
- Patients must have LBCL histologically confirmed by the local pathology laboratory, including one of the following types defined by the 2022 WHO Classification of Lymphoid Neoplasms. A central review of pathology is not required prior to study enrollment.
a. Diffuse LBCL (DLBCL) not otherwise specified (NOS), including germinal center B-cell (GCB) type or active B-cell (ABC) type
b. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma)
c. High-grade B-cell lymphoma, NOS
d. DLBCL arising from follicular lymphoma (FL; transformed follicular lymphoma)
e. DLBCL arising from marginal zone lymphoma (MZL; transformed marginal zone lymphoma)
f. Primary mediastinal large B-cell lymphoma (PMBL)
g. FL, Grade 3B/follicular large B-cell lymphoma (FLBL)
- Patients must have relapsed or refractory disease after the last therapy defined as follows:
a. Progressive disease (PD)/stable disease (SD) after the last therapy OR
b. Relapsed disease following a CR or progressive disease following a partial response (PR) after the last therapy.
- Patients must have at least one radiographically measurable lesion according to Lugano criteria.
a. Radiographically measurable disease is defined as at least 1 bi-dimensionally measurable nodal lesion of > 1.5 cm in its longest dimension, or at least 1 bi-dimensionally measurable extra nodal lesion of > 1.0 cm in its longest dimension.
b. Lesions that were previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
- Patients must have a washout period of at least 2 weeks or 5 half-lives, whichever is shorter, since any prior cancer therapy, at the time the patient undergoes leukapheresis, except as follows:
a. Prior bendamustine: a minimum of 6 months must have elapsed from the last infusion of bendamustine to enrollment in the current study.
b. Prior CD19-directed CAR T-cell therapy: a minimum of 30 days must have elapsed between the CD19-directed CAR T-cell infusion and enrollment to the current study.
c. Prior bispecific T-cell engaging antibody therapy: a minimum of 30 days must have elapsed between the last dose of bispecific T-cell engaging antibody therapy and enrollment to the current study.
d. Autologous stem cell transplant: a minimum of 6 weeks must have elapsed from the stem cell infusion to enrollment to the current study.
e. Central nervous system (CNS) prophylaxis (eg, intrathecal methotrexate): must be stopped at least 1 week prior to enrollment on the current study.
f. Prior corticosteroids: a minimum of 7 days prior to leukapheresis.
- Patients must have a tumor tissue biopsy sample following the most recent therapy available for central pathology evaluation; results of this evaluation do not need to be available prior to enrollment. A formalin-fixed paraffin-embedded tissue block, unstained slides, or a fresh biopsy provided in neutral buffered formalin, along with a corresponding local pathology report indicating CD19, CD20, and CD22 expression is required for submission to the Sponsor s central pathology laboratory.
a. Brushings, cell pellets from effusions or ascites and lavage, and previously stained slides are not acceptable.
b. Archival tissue from prior biopsies may also be submitted to the Sponsor central pathology lab in addition to the required biopsy material.
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Patients must have adequate hematologic and end-organ function, defined as follows:
a. Absolute neutrophil count (ANC) >= 1000/microL
b. Platelet count >= 75,000/microL or >= 50,000/microL in patients with known presence of marrow disease.
c. Absolute lymphocyte count (ALC) >= 100/microL.
d. Estimated creatinine clearance >= 45 mL/minute by Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) method or on the basis of 24-hour urine collection, or other institutional standard methods.
e. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <= 2.5 times the institutional upper limit of normal (ULN).
f. Total bilirubin <= 1.5 mg/dL (except in patients with Gilbert syndrome).
g. Cardiac left ventricular ejection fraction (LVEF) >= 45% and no evidence of pericardial effusion.
h. Blood oxygen saturation (SaO2) > 92% on room air.
i. Serum albumin >= 2.5 g/dL.
- Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after conditioning chemotherapy or CRG-022. Woman must agree to refrain from donating eggs during the same period.
a. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
b. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
c. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
d. Women of childbearing potential must have a negative pregnancy test result within 7 days prior to leukapheresis. Women who are considered not to be of childbearing potential are not required to have a pregnancy test.
- Men must agree to be abstinent (refrain from heterosexual intercourse) or use a condom with spermicide in combination with a highly effective method of contraception by a partner and agreement to not donate sperm.
a. With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom with spermicide during the treatment period and for at least 12 months after the last dose of conditioning chemotherapy of CRG-022. Men must refrain from donating sperm during this same period.
b. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure.
c. A condom is required to be used also by vasectomized men, as well as during intercourse with a male partner, in order to prevent delivery of the drug via seminal fluid.
d. Male patients considering preservation of fertility should bank sperm before study treatment.
- Patients must be, in the Investigator s judgment, able and willing to comply with the study protocol.
- Patients must be willing and able to remain within 1 hour of the treating center for at least 4 weeks after infusion.
- Patients must be stable or have recovered from non-hematologic toxicities due to prior therapy to
Grade <= 1 (except for clinically non significant toxicities such as alopecia).
Exclusion Criteria
Patients are excluded from the study if any of the following criteria apply:
- Patients who have a history of malignancy other than the lymphoma under investigation in this study, except that patients with the following malignancies/treatment characteristics are eligible:
a. Patients with a history of malignancy that has been treated with curative intent at least 2 years prior to screening and with no evidence of relapse if no concurrent anti-cancer therapy (except hormonal therapy) is being given.
b. Patients with a history of malignancy with a negligible risk of metastasis or death (eg, 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer.
c. Patients who have prostate cancer with no evidence of metastatic disease and are not on active therapy, except anti-androgen therapy.
- Patients with active fungal, bacterial, viral, or other infection. Prophylactic antimicrobials are allowed.
- Patients who received prior allogeneic stem cell, organ transplant, or allogeneic CAR therapy.
- Patients who received prior anti-CD52 antibody therapy.
- Patients with history of CNS involvement of lymphoma within 1 year prior to enrollment.
- Patients with ongoing cardiac involvement of lymphoma.
- Patients with a history of CD22-directed therapy for lymphoma.
- Patients with a history of infection with any of the following: human immunodeficiency virus (HIV); hepatitis B virus (HBV), as determined by positivity for hepatitis B serum antigen (HbsAg) or hepatitis B core antibody (HbcAb); or hepatitis C virus (HCV), as determined by positivity for anti-HCV antibody.
a. A patient with a history of infection with HBV or HCV may enroll if viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
- Patients with significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including the following:
a. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, serious cardiac arrhythmia or other clinically significant cardiac disease within 12 months prior to enrollment.
b. Active pulmonary disease (such as severe obstructive pulmonary disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis). History of limited radiation pneumonitis is allowed.
c. Clinically significant liver disease, including cirrhosis.
d. Clinically significant neurological disease (such as cerebrovascular ischemia/hemorrhage, dementia, seizure disorder, or cerebellar disease).
- Patients with a history of autoimmune disease resulting in significant end-organ disease or requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years.
a. Physiologic dose of steroid (prednisone <= 7.5 mg/day or equivalent) is acceptable.
b. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
c. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
d. Patients with history of immune thrombocytopenic purpura or autoimmune hemolytic anemia not requiring active treatment may be eligible.
- Patients with evidence of moderate to severe forms of primary immunodeficiencies.
- Patients with a history of severe, immediate hypersensitivity reaction attributed to aminoglycosides or any of the agents used in this study (eg, dimethyl sulfoxide [DMSO], tocilizumab).
- For women: pregnant or breastfeeding.
- Patients who underwent recent major surgery (within 4 weeks prior to leukapheresis), other than for diagnosis.
- Patients with any in-dwelling line or drain (eg, percutaneous nephrostomy tube, in dwelling Foley catheter, biliary drain). Dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted.
- Patients with a history of symptomatic deep vein thrombosis or pulmonary embolism requiring anticoagulation therapy within 6 months prior to enrollment.
- Patients who received treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study treatment or are anticipated to need such a vaccine during the post-treatment period (ie, up to 24 months post-infusion).
- Patients with Richter s transformation of chronic lymphatic leukemia (CLL).
- Patients with T-cell/histiocyte-rich large B-cell lymphoma. Patients with Burkitt lymphoma.
- Patients who require urgent therapy due to mass effects of tumor of impending oncologic emergency (eg, bowel obstruction, major blood vessel compression or tumor lysis syndrome).
- Patients with any other significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results.
- Patients who, in the Investigator s judgment, are unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
- Patients being treated concurrently with any other investigational agent, except for the investigational product under study (ie, CRG-022). Examples of other investigational products that would be exclusionary include supportive care agents like investigational antifungals.
- Patients who require growth factor support or platelet transfusion within the past 7 days to satisfy ANC or platelet count eligibility criteria.
Cohort-Specific Criteria
Cohort 1 (CD19-CAR T-Cell Therapy Exposed/T-Cell Engager Naive):
- Prior treatment with a CD19-directed CAR T-cell therapy. Commercially approved and experimental autologous CD19-directed CAR T-cell products are acceptable.
- No prior exposure to bispecific T-cell engaging antibody therapy (eg, mosunetuzumab, glofitamab, epcoritamab, etc).
Cohort 2 (Out of Specification):
- Patients eligible for any cohort in which the product is out of specification and deemed safe to administer.
Cohort 3 (CD19-CAR T-Cell Therapy Exposed/T-Cell Engager Exposed):
- Prior treatment with bispecific T-cell engaging antibody therapy (eg, mosunetuzumab, glofitamab, epcoritamab, etc).
Cohort 4 (CAR T-Cell Therapy Naive):
- No prior treatment with a CAR T-cell therapy including approved and experimental autologous CAR T-cell products.
- No more than 2 prior lines of therapy
-- Patients must have received at least 1 prior chemoimmunotherapy (CIT) containing regimen (ie, regimen must contain a CD20 targeted therapy plus an anthracycline).
-- Patients can be primary refractory to prior CIT or relapsed after PR or CR.
-- Prior bispecific T-cell engaging antibody therapy (eg, mosunetuzumab, glofitamab, epcoritamab, etc) containing regimens are allowed, however at least 30 days must have passed from the last dose to the time of leukapheresis.
Principal Investigator
Referral Contact
For more information: