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Protocol Details

A First-In-Human, Open-Label, Multicenter Study of VOR33 in Patients with Acute Myeloid Leukemia who are at High-Risk for Leukemia Relapse following Hematopoietic Cell Transplantation

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




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


Population Exclusion(s)

Pregnant Women;


Morphological Complete Remission;
Cd33 Positive;
Stem Cell Transplant;
Allogeneic Transplant

Recruitment Keyword(s)



Leukemia, Myeloid, Acute;
Acute Myeloid Leukemia

Investigational Drug(s)


Investigational Device(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.


To test gene-edited donor stem cells (VOR33) with and without the drug Mylotarg (Trademark) in people with AML.


People aged 18 to 70 years who have AML and the cancer protein CD33. Healthy, matched stem cell donors are also needed.


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 (Trademark) 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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1. Patients must be >=18 and <=70 years of age.

2. 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.

3. Patients must have confirmed diagnosis of AML according to WHO classification criteria

4. The patient s AML must have evidence of CD33 expression (>0%) according to institutional flow cytometry criteria.

5. Patients 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.

6. Patients must be a candidate (per Investigator opinion) for HLA-matched allogeneic HCT using a myeloablative conditioning regimen (see protocol for allowed regimens).

7. Patients must have a related or unrelated healthy stem cell donor that is a 10/10 match for HLAA, -B, -C, -DRB1, and -DQB1, as assessed by high-resolution DNA-based typing. The search for and selection of matched related and unrelated donors is per institutional standards.

8. Patients exceeding a weight of 120 kg (265 lbs) may participate with Sponsor Medical Monitor approval.

9. Patients must have adequate performance status and organ function as defined below:

-Performance Status: Karnofsky score of >=70.

-Cardiac: (LVEF) >=45% by ECHO or radionuclide scan (i.e., MUGA scan).

-Pulmonary: DLCO >=66% (adjusted for Hgb levels) and FVC and FEV1 >=66%.

-Renal: estimated GFR >60 mL/min as assessed by Cockcroft-Gault formula and actual body weight.

-Hepatic: total bilirubin <1.5 X ULN, or if >=1.5 X ULN direct bilirubin <ULN and ALT/AST <1.5 X ULN (per institutional criteria).

10. 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 (Trademark)). Examples of birth control methods are as follows: implants, injectables, combined oral contraceptives, IUDs, or vasectomized partner.

11. Up to 90 days after receiving the final dose of VOR33 or Mylotarg (Trademark)), 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 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.

12. Currently not requiring systemic corticosteroid therapy (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed).


1. Patients with TT genotype (SNP rs12459419; a population variation missing Mylotarg (Trademark) binding epitope on CD33)

2. Prior autologous or allogeneic stem cell transplantation.

3. 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.

4. Prior treatment with Mylotarg (Trademark) (gemtuzumab ozogamicin).

5. Active CNS leukemia.

6. Patients diagnosed with Gilbert s syndrome.

7. Uncontrolled bacterial, viral, or fungal infections; or known HIV, Hepatitis B, or Hepatitis C infection. (Patients cured of Hepatitis C for >=3 years prior to enrollment are permitted.)

8. Known sensitivity to components of CliniMACS (Registered Trademark) Prodigy CD34 System or VOR33, including iron dextran or murine proteins.

9. 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.

10. Women who are pregnant or who are lactating.

11.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.

12. 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 NYHA class III-IV).

13. 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.


1. Donors must be >=18 years of age and <=60 years of age (if unrelated), or if related, upper age limit based on NMDP guidelines at the time of donation.

2. 10/10 HLA-matched to the patient (HLA-A, -B, -C, -DRB1, and -DQB1).

3. Willing to receive injections of 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.

4. Willing and able to donate within the continental United States.

5. 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 630.20) may still be considered for donation by the Investigator with Sponsor Medical Monitor approval.

6. Meet additional criteria for donation as per NMDP or clinical trial site-specific requirements.

7. Willing and able to comply with the protocol procedures, in the opinion of the Investigator.

8. Willing and able to provide informed consent.


1. 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.

2. Sensitivity to filgrastim or to Escherichia coli-derived recombinant protein products.

3. 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.

4. History of deep vein thrombosis or pulmonary embolism.

5. History of iritis or episcleritis.

6. Platelet count <150,000/microL at baseline evaluation.

7. Current treatment with lithium. Drug interactions between filgrastim and lithium, which may potentiate the release of neutrophils, have not been fully evaluated.

8. Positive hemoglobin-solubility (e.g., SickleDex (Trademark) or equivalent) test.

9. Donors receiving experimental therapy or investigational agents within 30 days of the start of conditioning. FDA-approved therapies under investigation for alternative uses are permitted.

10. Donors deemed not medically suitable per the NMDP, the clinical trial site, or in the opinion of the Sponsor Medical Monitor.

11. Donors that do not meet the eligibility requirements per the NMDP or clinical trial site specific procedures, unless otherwise approved to donate by the Sponsor Medical Monitor and patient s physician.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Nirali N. Shah, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
(240) 760-6970

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

(240) 760-6970

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

Clinical Trials Number:


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