This study is currently recruiting participants.
Number
000731-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 70 Years
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Children
Keywords
Morphological Complete Remission; Cd33 Positive; Stem Cell Transplant; Allogeneic Transplant
Recruitment Keyword(s)
None
Condition(s)
Leukemia, Myeloid, Acute; Acute Myeloid Leukemia
Investigational Drug(s)
Busulfan Fludarabine
Investigational Device(s)
Intervention(s)
Drug: Mylotarg Biological/Vaccine: VOR33
Supporting Site
National Cancer Institute
Acute myeloid leukemia (AML) is a fast-growing cancer of the blood and bone marrow. It is the most common form of leukemia in adults and the second most common in children. AML is fatal without treatment. Blood stem cell transplants are a common treatment for AML, but complications and relapses often occur. Better treatments are needed.
Objective:
To assess the overall safety of VOR33 as determined by the incidence of successful neutrophil recovery 28 days after HCT in patients who have received VOR33.
Eligibility:
People aged 18 to 70 years who have AML and the cancer protein CD33.
Design:
Participants 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 and lung function. They will answer questions about their activities of daily life. These tests may be repeated throughout the study.
Donor stem cells will be modified to remove the gene that makes the CD33 protein.
Participants will be admitted to the hospital up to 10 days before receiving the VOR33. They will have chemotherapy. Then they will receive the VOR33 through a needle placed in a vein.
Participants will stay in the hospital for up to 28 days after the transplant. They will have daily blood tests until they have recovered enough to go home.
Participants may begin receiving Mylotarg 60 to 120 days after the transplant.
Participants will have follow-up visits for 2 years after their transplant. They may enroll in a separate follow-up study that will continue to monitor them for 13 more years.
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INCLUSION CRITERIA: -Patients must be >=18 and <=70 years of age. -Ability to understand and willingness to sign the informed consent form (ICF), or if applicable, understanding and willingness of the patient s caregiver or legally authorized representative prior to initiation of any study-related tests or procedures. -Patients must have confirmed diagnosis of AML or MDS according to WHO classification criteria. -The patient s AML or MDS must have evidence of CD33 expression (>0%) according to institutional flow cytometry criteria. -Patients with AML must have one of the following groups of features that are known to be a risk factor for leukemia relapse: --BM in morphological remission (<5% blasts) with adverse-risk disease-related genetics at presentation (according to ELN guidelines, or --Intermediate risk genetics in morphologic remission (<5% blasts) with other recognized high risk criteria such as MRD+ following therapy, or --BM with evidence of persistent leukemia 5-10% blasts post induction/salvage therapy. Patients with BM blast count > 10% may participate with Sponsor Medical Monitor approval. (Note: these patients may have disease-related genetics of any risk criteria at presentation), or --Any patient in second or greater remission. --Patients with MDS must have all of the following: ---Previous or current IPSS-R score of High or Very High risk; AND ---Previous or current MDS-IB1 or MDS-IB2 per the 2022 WHO criteria. -Patients must be a candidate (per Investigator opinion) for HLA-matched allogeneic HCT using a myeloablative conditioning regimen (see protocol for allowed regimens). -Patients must have a related or unrelated stem cell donor that is an 8/8 match for HLA-A, -B, -C, and -DRB1, as assessed by high-resolution DNA-based typing. The selection of related donors is per institutional standards and for unrelated donors is per Registry standards. -Patients exceeding a weight of 120 kg (265 lbs) may participate with Sponsor Medical Monitor approval. -Patients must have adequate performance status and organ function as defined below: --Performance Status: Karnofsky score of >=70. -Cardiac: Left ventricular ejection fraction (LVEF) >=45% by echocardiogram (ECHO) or radionuclide scan (i.e., multiple-gated acquisition [MUGA] scan). --Pulmonary: Diffuse capacity of lung for carbon monoxide (DLCO) >=66% (adjusted for hemoglobin [Hgb] levels) and forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) >=66%. --Renal: estimated glomerular filtration rate (GFR) >60 mL/min as assessed by Cockcroft-Gault formula and actual body weight. --Hepatic: total bilirubin <1.5 (SqrRoot) ULN, or if >=1.5 (SqrRoot) ULN, direct bilirubin <ULN and ALT/AST <1.5 (SqrRoot) ULN (per institutional criteria). -Female patients of childbearing potential must test negative for pregnancy at screening, not be pregnant, nor breastfeeding, nor expecting to conceive within the projected duration of the trial. Sexually active women, unless surgically sterile, must be willing to use a highly effective method of birth control up to 180 days post last dose of study drug (VOR33 or Mylotarg(TM)). Examples of birth control methods are as follows: implants, injectables, combined oral contraceptives, IUDs, or vasectomized partner. -Up to 90 days after receiving the final dose of VOR33 or Mylotarg(TM), male patients with partners of childbearing potential must be either vasectomized or agree to use a condom, in addition to having their partners use another method of contraception resulting in a highly effective method of birth control such as implants, injectables, combined oral contraceptives, or intra-uterine devices (IUDs). Male patients should not have sexual intercourse with females who are either pregnant or lactating without double-barrier contraception. Male patients must not donate sperm during the course of the study. -Currently not requiring systemic corticosteroid therapy (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed). EXCLUSION CRITERIA: -Patients with TT genotype (single nucleotide polymorphism [SNP] rs12459419; a population variation missing Mylotarg(TM) binding epitope on CD33). -Prior autologous or allogeneic stem cell transplantation. -Presence of the following disease-related genetics: t(15; 17)(q22; q21), or t(9; 22)(q34; q11), or other evidence of acute promyelocytic leukemia or chronic myeloid leukemia. -Prior treatment with Mylotarg(TM) (gemtuzumab ozogamicin) in the past 3.5 months, except with Medical Monitor approval, or any prior Mylotarg(TM)-related SOS/VOD. -Active central nervous system (CNS) leukemia. -Patients diagnosed with Gilbert s syndrome. -Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection. (Patients cured of Hepatitis C for >=3 years prior to enrollment are permitted.) -Known sensitivity to components of CliniMACS(R) Prodigy CD34 System or VOR33, including iron dextran or murine proteins. -Have a history of other active malignancy(ies) unless the patient has been disease-free for at least 2 years and is deemed by the treating Investigator to be at low risk for recurrence of that malignancy; or the only prior cancer is curatively treated cervical cancer in situ, or basal cell or squamous cell carcinoma of the skin. -Women who are pregnant or who are lactating. -Received any investigational drug (that is, an agent that has not received regulatory approval for any indication) within the 30 days prior to the start of conditioning unless approved by the Sponsor Medical Monitor. -History of cardiovascular disease including but not limited to myocardial infarction, unstable angina, stroke, or transient ischemic attack within the 6 months prior to the initiation of study or congestive heart failure (New York Heart Association [NYHA] class III-IV). -Any serious underlying medical or psychiatric condition that would increase the risk associated with study participation, in the opinion of the Investigator or Sponsor Medical Monitor. INCLUSION CRITERIA (DONOR): -Donors must be >=18 years of age. -8/8 HLA-matched to the patient (HLA-A, -B, -C, and -DRB1). -Willing to receive injections of granulocyte-colony stimulating factor (G-CSF) and plerixafor in order to stimulate the peripheral blood circulation of HSCs and donate hematopoietic progenitor cells by apheresis for up to 2 consecutive days. -Willing and able to donate within the United States. Related donors for patients in Canada may donate at clinical trial site(s) in Canada. -Meet the donor requirements under 21 Code of Federal Regulations (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 630.20) may still be considered for donation by the Investigator with Sponsor Medical Monitor approval. -Meet additional criteria for donation as per Registry, or clinical trial site-specific requirements. -Willing and able to comply with the protocol procedures, in the opinion of the Investigator or Registry. -Willing and able to provide informed consent. EXCLUSION CRITERIA (DONOR): -For female donors of childbearing potential: pregnancy, or uninterruptible breastfeeding. Pregnancy is an absolute contraindication under this protocol. Women who are breastfeeding must be willing and able to interrupt breastfeeding during G-CSF (filgrastim) and plerixafor administration and for 2 days following the final dose. -Sensitivity to filgrastim or to Escherichia coli-derived recombinant protein products. -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. -History of deep vein thrombosis or pulmonary embolism. -History of iritis or episcleritis. -Platelet count <150,000/microliter at baseline evaluation. -Current treatment with lithium. Drug interactions between filgrastim and lithium, which may potentiate the release of neutrophils, have not been fully evaluated. -Positive hemoglobin-solubility (e.g., SickleDex(TM) or equivalent) test. -Donors receiving experimental therapy or investigational agents within 30 days of the start of mobilization. FDA-approved therapies under investigation for alternative uses are permitted. -Donors deemed not medically suitable per the Registry, the clinical trial site, or in the opinion of the Sponsor Medical Monitor. -Donors that do not meet the eligibility requirements per the Registry, or clinical trial site specific procedures, unless otherwise approved to donate by the Sponsor Medical Monitor and patient s physician.
-Patients must be >=18 and <=70 years of age.
-Ability to understand and willingness to sign the informed consent form (ICF), or if applicable, understanding and willingness of the patient s caregiver or legally authorized representative prior to initiation of any study-related tests or procedures.
-Patients must have confirmed diagnosis of AML or MDS according to WHO classification criteria.
-The patient s AML or MDS must have evidence of CD33 expression (>0%) according to institutional flow cytometry criteria.
-Patients with AML must have one of the following groups of features that are known to be a risk factor for leukemia relapse:
--BM in morphological remission (<5% blasts) with adverse-risk disease-related genetics at presentation (according to ELN guidelines, or
--Intermediate risk genetics in morphologic remission (<5% blasts) with other recognized high risk criteria such as MRD+ following therapy, or
--BM with evidence of persistent leukemia 5-10% blasts post induction/salvage therapy. Patients with BM blast count > 10% may participate with Sponsor Medical Monitor approval. (Note: these patients may have disease-related genetics of any risk criteria at presentation), or
--Any patient in second or greater remission.
--Patients with MDS must have all of the following:
---Previous or current IPSS-R score of High or Very High risk; AND
---Previous or current MDS-IB1 or MDS-IB2 per the 2022 WHO criteria.
-Patients must be a candidate (per Investigator opinion) for HLA-matched allogeneic HCT using a myeloablative conditioning regimen (see protocol for allowed regimens).
-Patients must have a related or unrelated stem cell donor that is an 8/8 match for HLA-A, -B, -C, and -DRB1, as assessed by high-resolution DNA-based typing. The selection of related donors is per institutional standards and for unrelated donors is per Registry standards.
-Patients exceeding a weight of 120 kg (265 lbs) may participate with Sponsor Medical Monitor approval.
-Patients must have adequate performance status and organ function as defined below:
--Performance Status: Karnofsky score of >=70.
-Cardiac: Left ventricular ejection fraction (LVEF) >=45% by echocardiogram (ECHO) or radionuclide scan (i.e., multiple-gated acquisition [MUGA] scan).
--Pulmonary: Diffuse capacity of lung for carbon monoxide (DLCO) >=66% (adjusted for hemoglobin [Hgb] levels) and forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) >=66%.
--Renal: estimated glomerular filtration rate (GFR) >60 mL/min as assessed by Cockcroft-Gault formula and actual body weight.
--Hepatic: total bilirubin <1.5 (SqrRoot) ULN, or if >=1.5 (SqrRoot) ULN, direct bilirubin <ULN and ALT/AST <1.5 (SqrRoot) ULN (per institutional criteria).
-Female patients of childbearing potential must test negative for pregnancy at screening, not be pregnant, nor breastfeeding, nor expecting to conceive within the projected duration of the trial. Sexually active women, unless surgically sterile, must be willing to use a highly effective method of birth control up to 180 days post last dose of study drug (VOR33 or Mylotarg(TM)). Examples of birth control methods are as follows: implants, injectables, combined oral contraceptives, IUDs, or vasectomized partner.
-Up to 90 days after receiving the final dose of VOR33 or Mylotarg(TM), male patients with partners of childbearing potential must be either vasectomized or agree to use a condom, in addition to having their partners use another method of contraception resulting in a highly effective method of birth control such as implants, injectables, combined oral contraceptives, or intra-uterine devices (IUDs). Male patients should not have sexual intercourse with females who are either pregnant or lactating without double-barrier contraception. Male patients must not donate sperm during the course of the study.
-Currently not requiring systemic corticosteroid therapy (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed).
EXCLUSION CRITERIA:
-Patients with TT genotype (single nucleotide polymorphism [SNP] rs12459419; a population variation missing Mylotarg(TM) binding epitope on CD33).
-Prior autologous or allogeneic stem cell transplantation.
-Presence of the following disease-related genetics: t(15; 17)(q22; q21), or t(9; 22)(q34; q11), or other evidence of acute promyelocytic leukemia or chronic myeloid leukemia.
-Prior treatment with Mylotarg(TM) (gemtuzumab ozogamicin) in the past 3.5 months, except with Medical Monitor approval, or any prior Mylotarg(TM)-related SOS/VOD.
-Active central nervous system (CNS) leukemia.
-Patients diagnosed with Gilbert s syndrome.
-Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection. (Patients cured of Hepatitis C for >=3 years prior to enrollment are permitted.)
-Known sensitivity to components of CliniMACS(R) Prodigy CD34 System or VOR33, including iron dextran or murine proteins.
-Have a history of other active malignancy(ies) unless the patient has been disease-free for at least 2 years and is deemed by the treating Investigator to be at low risk for recurrence of that malignancy; or the only prior cancer is curatively treated cervical cancer in situ, or basal cell or squamous cell carcinoma of the skin.
-Women who are pregnant or who are lactating.
-Received any investigational drug (that is, an agent that has not received regulatory approval for any indication) within the 30 days prior to the start of conditioning unless approved by the Sponsor Medical Monitor.
-History of cardiovascular disease including but not limited to myocardial infarction, unstable angina, stroke, or transient ischemic attack within the 6 months prior to the initiation of study or congestive heart failure (New York Heart Association [NYHA] class III-IV).
-Any serious underlying medical or psychiatric condition that would increase the risk associated with study participation, in the opinion of the Investigator or Sponsor Medical Monitor.
INCLUSION CRITERIA (DONOR):
-Donors must be >=18 years of age.
-8/8 HLA-matched to the patient (HLA-A, -B, -C, and -DRB1).
-Willing to receive injections of granulocyte-colony stimulating factor (G-CSF) and plerixafor in order to stimulate the peripheral blood circulation of HSCs and donate hematopoietic progenitor cells by apheresis for up to 2 consecutive days.
-Willing and able to donate within the United States. Related donors for patients in Canada may donate at clinical trial site(s) in Canada.
-Meet the donor requirements under 21 Code of Federal Regulations (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 630.20) may still be considered for donation by the Investigator with Sponsor Medical Monitor approval.
-Meet additional criteria for donation as per Registry, or clinical trial site-specific requirements.
-Willing and able to comply with the protocol procedures, in the opinion of the Investigator or Registry.
-Willing and able to provide informed consent.
EXCLUSION CRITERIA (DONOR):
-For female donors of childbearing potential: pregnancy, or uninterruptible breastfeeding. Pregnancy is an absolute contraindication under this protocol. Women who are breastfeeding must be willing and able to interrupt breastfeeding during G-CSF (filgrastim) and plerixafor administration and for 2 days following the final dose.
-Sensitivity to filgrastim or to Escherichia coli-derived recombinant protein products.
-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.
-History of deep vein thrombosis or pulmonary embolism.
-History of iritis or episcleritis.
-Platelet count <150,000/microliter at baseline evaluation.
-Current treatment with lithium. Drug interactions between filgrastim and lithium, which may potentiate the release of neutrophils, have not been fully evaluated.
-Positive hemoglobin-solubility (e.g., SickleDex(TM) or equivalent) test.
-Donors receiving experimental therapy or investigational agents within 30 days of the start of mobilization. FDA-approved therapies under investigation for alternative uses are permitted.
-Donors deemed not medically suitable per the Registry, the clinical trial site, or in the opinion of the Sponsor Medical Monitor.
-Donors that do not meet the eligibility requirements per the Registry, or clinical trial site specific procedures, unless otherwise approved to donate by the Sponsor Medical Monitor and patient s physician.
Principal Investigator
Referral Contact
For more information: