This study is NOT currently recruiting participants.
Number
001784-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Recruitment has not started Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Pregnant Women;Fetuses;Neonates
Keywords
Leukemia; Acute Myeloid Leukemia; AML; Hematopoietic Stem Cell Transplant; HCT; Cd33; Allogeneic; CAR T
Recruitment Keyword(s)
None
Condition(s)
Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases
Investigational Drug(s)
VCAR33
Investigational Device(s)
Intervention(s)
Biological/Vaccine: VCAR33 Drug: Fludarabine Drug: Cyclophosphamide
Supporting Site
National Cancer Institute
Acute myeloid leukemia (AML) is a fast-growing cancer of the blood and bone marrow. The only cure for AML is hematopoietic cell transplant (HCT) using donor stem cells (alloHCT). But up to 60% of patients relapse after treatment. Many AML cells have a surface protein called CD33. Researchers want to try treating people with AML using a study product (VCAR33) that targets and kills cells that have CD33.
Objective:
To test VCAR33 in people with advanced AML.
Eligibility:
People aged 18 years and older with AML that returned after alloHCT. Their original alloHCT donor must be available.
Design:
Participants with AML will be screened. They will have a physical exam with blood and urine tests. They will have chest X-rays and tests of their heart function. They may have a bone marrow biopsy: A sample of soft tissue will be removed from inside a bone.
Donors will undergo apheresis: Blood will be taken from the body through a tube attached to a needle. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be returned to the body. The white blood cells will undergo gene therapy to create VCAR33.
Participants with AML will stay in the hospital for at least 12 days. For the first 5 days, they will take drugs to prepare them for treatment. Then they will receive VCAR33 by infusion into a vein.
After discharge, participants will take their temperature every 6 to 8 hours until day 28.
Follow-up visits will continue for 2 years.
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INCLUSION CRITERIA: Each patient must meet the following criteria to be enrolled in this study: 1. Patients aged >= 18 years 2. Patients must have CD33+ AML in relapse or refractory after alloHCT 3. Patients must be a recipient of an 8/8 (A, B, C, DRB1) HLA-matched related or unrelated donor alloHCT. Patients previously transplanted with VOR33 in the VBP101 study who have R/R AML may also be considered. 4. Disease status at the time of enrollment: a. Arm A/Morphologic disease: Defined as >= 5% blasts (bone marrow) post-HCT b. Arm B/MRD positive: < 5% blasts (bone marrow) with minimal residual disease of at least 0.1% CD33+ leukemia cells by flow cytometry 5. Performance status: ECOG 0 or 1 6. Patient must have adequate organ function as defined by: a. Cardiac: Left ventricular ejection fraction (LVEF) >= 45% or fractional shortening >= 28% b. Pulmonary: Baseline oxygen saturation > 92% on room air at rest c. Hepatic: Total bilirubin < 3x institutional upper limit of normal (ULN) (except in case of patients with documented Gilbert s disease < 5x ULN) and aspartate aminotransferase (AST/SGOT)/alanine aminotransferase (ALT/SGPT) < 5x institutional ULN d. Renal: Serum creatinine must be <= 1.2x institutional ULN or creatinine clearance (Bullet) 60 mL/min for patients with creatinine levels above institutional normal 7. Original alloHCT donor is available and willing to undergo apheresis 8. Patient must have an option to proceed to a second alloHCT in case stem cell rescue is needed for prolonged aplasia, with a cryopreserved back-up graft available OR an allogeneic HCT donor identified. The allogeneic HCT donor for this second transplant may be the same or different donor as for the first transplant, at the Investigator s discretion. EXCLUSION CRITERIA: Patients who meet any of the following criteria will be excluded from the study. 1. Patients who have undergone more than one alloHCT 2. Patients who have undergone alloHCT with a mismatched unrelated donor, haploidentical donor, or with umbilical cord blood as the stem cell source 3. Patients who will be less than 100 days post-alloHCT at the time of VCAR33 infusion. 4. Patients with any history of Grade III or IV acute GVHD or severe chronic GVHD unless approved by the Sponsor Medical Monitor 5. Patients with evidence of ongoing active acute or chronic GVHD and are taking systemic immunosuppressive agents (> 10 mg daily of prednisone equivalent or other GVHD-directed treatment, including extracorporeal photopheresis). Patients with Grade 1 acute GVHD limited to the skin or mild chronic GVHD limited to the eyes, mouth, or skin controlled with only topical therapy are eligible. 6. Patients with active CNS disease. A lumbar puncture is not required to exclude CNS disease in the absence of clinical signs or symptoms suggesting CNS disease. 7. Patients with hyperleukocytosis (for example, >= 30,000 blasts/microL) or rapidly progressive disease. Hydroxyurea is permitted prior to the start of LD to control blast counts. 8. Patients with the following prior therapy: - DLI within 28 days prior to enrollment - Prior treatment with any CAR T cell therapy product 9. Patients with active or uncontrolled viral, bacterial, or fungal infection 10. Patients with a history of a human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection 11. Patients with a history of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, or breast) unless disease free for at least 3 years after the last definitive therapy 12. Female patients of childbearing potential who are pregnant or breastfeeding 13. Patients with a history of severe hypersensitivity reaction to aminoglycosides Pre-Treatment Criteria Prior to the Start of LD Patients who meet any of the following criteria prior to the start of LD should be withdrawn from the study and should not receive LD. 1. Patients who are receiving active immunosuppression for GVHD prophylaxis should be off immunosuppression for 28 days prior to planned start of LD, unless approved by the Sponsor Medical Monitor. 2. Any bridging therapy must be stopped within 14 days prior to the start of LD, with the exception of hydroxyurea and other lower intensity chemotherapy agents 3. There must be a 4 week washout period between the last dose of any CD33 directed therapy and the VCAR33 infusion. 4. VCAR33 must have met release criteria 5. Performance status: ECOG 0 or 1 6. Adequate cardiopulmonary status without need for vasoactive or supplemental oxygen support 7. No signs of new uncontrolled infection 8. Adequate renal and hepatic function as defined in the Inclusion Criteria 9. No evidence of rapidly progressive AML (defined by any of the following: a) doubling of absolute peripheral blast count with a threshold of > 30,000/microL, b) having new signs and symptoms concerning for new CNS involvement which would prompt further evaluation, c) per local PI designation). 10. Echocardiogram (per PI discretion) 11. Disease evaluation (bone marrow aspirate/biopsy) must be performed within 2 weeks of lymphodepletion start. Donor Eligibility Criteria Inclusion Criteria (Donor) 1. Donors must be >=18 years of age and <=60 years of age (if unrelated), or if related, upper age limit based on site-specific guidelines at the time of donation. 2. 8/8 HLA-matched to the patient (HLA-A, -B, -C, -DRB1). 3. Willing and able to donate within the continental United States. 4. Meet the donor requirements under 21 CFR 1271 and related August 2007 guidance regarding the Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products. Donors considered ineligible but suitable (per CFR section 630.20) may still be considered for donation by the Investigator with Sponsor Medical Monitor approval. 5. Meet any additional criteria for donation as per clinical site-specific requirements. Exclusion Criteria (Donor) 1. For female donors of childbearing potential, pregnancy, or uninterruptible breastfeeding. Pregnancy is an absolute contraindication under this protocol. 2. History of autoimmune disorders, including rheumatic diseases and thyroid disorders (though donors with a history of thyroid disease who have undergone successful therapy may be suitable). Exemptions for mild or limited disease may be granted after discussion with the Investigator and Sponsor s Medical Monitor. 3. History of deep vein thrombosis or pulmonary embolism. 4. Platelet count <150,000/microL at baseline evaluation. 5. Donors receiving experimental therapy or investigational agents within 28 days of apheresis. 6. Donors deemed not medically suitable. 7. Donors that do not meet the eligibility requirements per the local site procedures. 8. Inability or unwillingness to comply with protocol procedures. 9. Inability or unwillingness to provide informed consent.
Each patient must meet the following criteria to be enrolled in this study:
1. Patients aged >= 18 years
2. Patients must have CD33+ AML in relapse or refractory after alloHCT
3. Patients must be a recipient of an 8/8 (A, B, C, DRB1) HLA-matched related or unrelated donor alloHCT. Patients previously transplanted with VOR33 in the VBP101 study who have R/R AML may also be considered.
4. Disease status at the time of enrollment:
a. Arm A/Morphologic disease: Defined as >= 5% blasts (bone marrow) post-HCT
b. Arm B/MRD positive: < 5% blasts (bone marrow) with minimal residual disease of at least 0.1% CD33+ leukemia cells by flow cytometry
5. Performance status: ECOG 0 or 1
6. Patient must have adequate organ function as defined by:
a. Cardiac: Left ventricular ejection fraction (LVEF) >= 45% or fractional shortening >= 28%
b. Pulmonary: Baseline oxygen saturation > 92% on room air at rest
c. Hepatic: Total bilirubin < 3x institutional upper limit of normal (ULN) (except in case of patients with documented Gilbert s disease < 5x ULN) and aspartate aminotransferase (AST/SGOT)/alanine aminotransferase (ALT/SGPT) < 5x institutional ULN
d. Renal: Serum creatinine must be <= 1.2x institutional ULN or creatinine clearance (Bullet) 60 mL/min for patients with creatinine levels above institutional normal
7. Original alloHCT donor is available and willing to undergo apheresis
8. Patient must have an option to proceed to a second alloHCT in case stem cell rescue is needed for prolonged aplasia, with a cryopreserved back-up graft available OR an allogeneic HCT donor identified. The allogeneic HCT donor for this second transplant may be the same or different donor as for the first transplant, at the Investigator s discretion.
EXCLUSION CRITERIA:
Patients who meet any of the following criteria will be excluded from the study.
1. Patients who have undergone more than one alloHCT
2. Patients who have undergone alloHCT with a mismatched unrelated donor, haploidentical donor, or with umbilical cord blood as the stem cell source
3. Patients who will be less than 100 days post-alloHCT at the time of VCAR33 infusion.
4. Patients with any history of Grade III or IV acute GVHD or severe chronic GVHD unless approved by the Sponsor Medical Monitor
5. Patients with evidence of ongoing active acute or chronic GVHD and are taking systemic immunosuppressive agents (> 10 mg daily of prednisone equivalent or other GVHD-directed treatment, including extracorporeal photopheresis). Patients with Grade 1 acute GVHD limited to the skin or mild chronic GVHD limited to the eyes, mouth, or skin controlled with only topical therapy are eligible.
6. Patients with active CNS disease. A lumbar puncture is not required to exclude CNS disease in the absence of clinical signs or symptoms suggesting CNS disease.
7. Patients with hyperleukocytosis (for example, >= 30,000 blasts/microL) or rapidly progressive disease. Hydroxyurea is permitted prior to the start of LD to control blast counts.
8. Patients with the following prior therapy:
- DLI within 28 days prior to enrollment
- Prior treatment with any CAR T cell therapy product
9. Patients with active or uncontrolled viral, bacterial, or fungal infection
10. Patients with a history of a human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection
11. Patients with a history of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, or breast) unless disease free for at least 3 years after the last definitive therapy
12. Female patients of childbearing potential who are pregnant or breastfeeding
13. Patients with a history of severe hypersensitivity reaction to aminoglycosides
Pre-Treatment Criteria Prior to the Start of LD
Patients who meet any of the following criteria prior to the start of LD should be withdrawn from the study and should not receive LD.
1. Patients who are receiving active immunosuppression for GVHD prophylaxis should be off immunosuppression for 28 days prior to planned start of LD, unless approved by the Sponsor Medical Monitor.
2. Any bridging therapy must be stopped within 14 days prior to the start of LD, with the exception of hydroxyurea and other lower intensity chemotherapy agents
3. There must be a 4 week washout period between the last dose of any CD33 directed therapy and the VCAR33 infusion.
4. VCAR33 must have met release criteria
6. Adequate cardiopulmonary status without need for vasoactive or supplemental oxygen support
7. No signs of new uncontrolled infection
8. Adequate renal and hepatic function as defined in the Inclusion Criteria
9. No evidence of rapidly progressive AML (defined by any of the following: a) doubling of absolute peripheral blast count with a threshold of > 30,000/microL, b) having new signs and symptoms concerning for new CNS involvement which would prompt further evaluation, c) per local PI designation).
10. Echocardiogram (per PI discretion)
11. Disease evaluation (bone marrow aspirate/biopsy) must be performed within 2 weeks of lymphodepletion start.
Donor Eligibility Criteria
Inclusion Criteria (Donor)
1. Donors must be >=18 years of age and <=60 years of age (if unrelated), or if related, upper age limit based on site-specific guidelines at the time of donation.
2. 8/8 HLA-matched to the patient (HLA-A, -B, -C, -DRB1).
3. Willing and able to donate within the continental United States.
4. Meet the donor requirements under 21 CFR 1271 and related August 2007 guidance regarding the Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products. Donors considered ineligible but suitable (per CFR section 630.20) may still be considered for donation by the Investigator with Sponsor Medical Monitor approval.
5. Meet any additional criteria for donation as per clinical site-specific requirements.
Exclusion Criteria (Donor)
1. For female donors of childbearing potential, pregnancy, or uninterruptible breastfeeding. Pregnancy is an absolute contraindication under this protocol.
2. History of autoimmune disorders, including rheumatic diseases and thyroid disorders (though donors with a history of thyroid disease who have undergone successful therapy may be suitable). Exemptions for mild or limited disease may be granted after discussion with the Investigator and Sponsor s Medical Monitor.
3. History of deep vein thrombosis or pulmonary embolism.
4. Platelet count <150,000/microL at baseline evaluation.
5. Donors receiving experimental therapy or investigational agents within 28 days of apheresis.
6. Donors deemed not medically suitable.
7. Donors that do not meet the eligibility requirements per the local site procedures.
8. Inability or unwillingness to comply with protocol procedures.
9. Inability or unwillingness to provide informed consent.
Principal Investigator
Referral Contact
For more information: