LeukemiaPhase 1NCT00672165
Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies
A Phase 1 study testing ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195 in people with Leukemia and Myelodysplastic Syndrome, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to find a safe dose of actinium-225 when it is labeled to HuM195. This will be done with a "phase I trial," in which a preset schedule of doses gets more powerful for each new group of patients as the trial progresses. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukemia, Myelodysplastic Syndrome
- What is being tested?
- ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to Feb 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have one of the following pathologically confirmed diagnoses:
- AML in relapse,
- AML refractory to at least 2 courses of standard induction chemotherapy or one course of high-dose cytarabine-containing induction chemotherapy,
- CML in accelerated phase or myeloid blast crisis that has progressed after treatment with imatinib and a second generation tyrosine kinase inhibitor (e.g., dasatinib or nilotinib)
- RAEB with International Prognostic Scoring System (IPSS) score ≥ 2.5, or - CMMOL with IPSS score ≥ 2.5 refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine) refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine).
- Greater than 25% of bone marrow blasts must be CD33 positive.
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- Patients must have a life expectancy of at least 6 weeks and a Karnofsky performance status of ≥ 60%.
- Adequate renal function as demonstrated by a serum creatinine ≤ 1.5 mg/dl, a creatinine clearance > 60 ml/min, and < 1 gram urinary protein/24 hours.
- Adequate hepatic function as demonstrated by a bilirubin ≤ 1.5 mg/dl (unless attributable to leukemia or Gilbert's disease) and alkaline phosphatase and AST ≤ 2.5 times the upper limit of normal.
Who cannot join
- Untreated AML, regardless of prognostic features.
- Treatment with chemotherapy or biologic therapy within 3 weeks of 225Ac- HuM195 administration. Hydroxyurea is permitted but must be discontinued prior to treatment on study. Patients must have recovered from the effects of previous treatment.
- Treatment with radiation therapy within 6 weeks of 225Ac-HuM195 administration. Patients must have recovered from the effects of previous treatment.
- Active serious infections not controlled by antibiotics.
- Pregnant women or women who are breast-feeding.
- Concurrent active malignancy requiring therapy.
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- Clinically significant cardiac disease (NY Heart Association Class III or IV)or pulmonary disease.
- Patients with HLA-compatible donor bone marrow who are immediate candidates for bone marrow transplantation.
- Patients who are candidates for alternative treatments of known effectiveness.
- Patients eligible for protocols of higher priority.
- Patients previously treated with any monoclonal antibody for any reason.
- Active CNS leukemia
- Other serious or life-threatening conditions deemed unacceptable by the principal investigator.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase I Trial of Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies
The purpose of this study is to find a safe dose of actinium-225 when it is labeled to HuM195. This will be done with a "phase I trial," in which a preset schedule of doses gets more powerful for each new group of patients as the trial progresses. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some additional patients may be treated with a lower dose to make sure that this dose is safe. The starting dose of actinium-225 in this study is less than doses that are known to be safe in animals.
Antibodies are proteins that are produced by the immune system and help the body to fight foreign substances, such as bacteria or viruses. HuM195 was made by putting human leukemia cells into mice. Most of the mouse parts of this antibody were replaced with human parts. Only the part of the antibody that binds to the leukemia cells was kept from the mouse. HuM195 attaches to leukemia cells but does not attach to most normal cells. It can kill small amounts of disease by identifying the leukemia cells as "foreign." HuM195 has worked less well against large amounts of leukemia since the normal immune cells needed to kill leukemia cells are lowered in most patients with leukemia.
- Conditions
- Leukemia, Myelodysplastic Syndrome
- Being tested
- ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195
- Keywords
- MAB HUM 195 ACTINIUM-225 LABELED, HEMATOPOIETIC SYSTEM, 02-017
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195Biological
A single infusion of 225Ac-HuM195 will be administered at a starting dose of 0.5 μCi/kg. Additionally, 100 mCi of 213Bi-HuM195 have been administered with full dose cytarabine (200 mg/m2 daily for 5 days) without dose-limiting toxicity.Serial sampling of blood, urine, and bone marrow will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antileukemic effects. Three to six patients will be treated at each dose level. Dose escalation will proceed if less than 33% of patients in a cohort experience dose-limiting toxicity.Patients will be followed until completion of therapy as outlined in the study, loss to follow-up, death, or until the day the patient is removed from the study.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | This is a phase I, dose-escalation trial. The starting dose level will be 0.5 μCi/kg of 225Ac-HuM195. Three to six patients will be treated at each dose level, and dose escalation will proceed if less than 33% of patients in a cohort experience dose limiting toxicity. Six patients will be treated at the maximum tolerated dose Receives: Biological: ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of 225Ac-HuM195 that can be administered to patients with advanced myeloid leukemias.
Measured: conclusion of study
Secondary outcomes (2)
To determine the pharmacokinetics and dosimetry of 225Ac-HuM195.
Measured: conclusion of the study
To determine the biological effects of 225Ac-HuM195, including its ability to produce complete remissions.
Measured: conclusion of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2008 (estimated)
- Study startJul 2005
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Actinium Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Dan Douer, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00672165
- Sponsor's protocol ID
- 02-017
- Other IDs
- NCI CA33049
- Status last verified
- Feb 2015
- First submitted
- 2 May 2008
- Last updated
- 26 Feb 2015
- Results posted
- No
Publications
Nikitaki Z, Velalopoulou A, Zanni V, Tremi I, Havaki S, Kokkoris M, Gorgoulis VG, Koumenis C, Georgakilas AG. Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair. Expert Rev Mol Med. 2022 Mar 31;24:e15. doi: 10.1017/erm.2022.6.
PubMed 35357290
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies
- ClinicalTrials.gov ID
- NCT00672165
- Acronym / sponsor ID
- 02-017
- Conditions
- Leukemia, Myelodysplastic Syndrome
- Keywords
- MAB HUM 195 ACTINIUM-225 LABELED, HEMATOPOIETIC SYSTEM, 02-017
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Actinium Pharmaceuticals
- Study start
- Jul 2005
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 6 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find a safe dose of actinium-225 when it is labeled to HuM195. This will be done with a "phase I trial," in which a preset schedule of doses gets more powerful for each new group of patients as the trial progresses. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some additional patients may be treated with a lower dose to make sure that this dose is safe. The starting dose of actinium-225 in this study is less than doses that are known to be safe in animals.
Antibodies are proteins that are produced by the immune system and help the body to fight foreign substances, such as bacteria or viruses. HuM195 was made by putting human leukemia cells into mice. Most of the mouse parts of this antibody were replaced with human parts. Only the part of the antibody that binds to the leukemia cells was kept from the mouse. HuM195 attaches to leukemia cells but does not attach to most normal cells. It can kill small amounts of disease by identifying the leukemia cells as "foreign." HuM195 has worked less well against large amounts of leukemia since the normal immune cells needed to kill leukemia cells are lowered in most patients with leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195This is a phase I, dose-escalation trial. The starting dose level will be 0.5 μCi/kg of 225Ac-HuM195. Three to six patients will be treated at each dose level, and dose escalation will proceed if less than 33% of patients in a cohort experience dose limiting toxicity. Six patients will be treated at the maximum tolerated dose |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must have one of the following pathologically confirmed diagnoses:
- AML in relapse,
- AML refractory to at least 2 courses of standard induction chemotherapy or one course of high-dose cytarabine-containing induction chemotherapy,
- CML in accelerated phase or myeloid blast crisis that has progressed after treatment with imatinib and a second generation tyrosine kinase inhibitor (e.g., dasatinib or nilotinib)
- RAEB with International Prognostic Scoring System (IPSS) score ≥ 2.5, or - CMMOL with IPSS score ≥ 2.5 refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine) refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine).
Key exclusion criteria (13 listed)
- Untreated AML, regardless of prognostic features.
- Treatment with chemotherapy or biologic therapy within 3 weeks of 225Ac- HuM195 administration. Hydroxyurea is permitted but must be discontinued prior to treatment on study. Patients must have recovered from the effects of previous treatment.
- Treatment with radiation therapy within 6 weeks of 225Ac-HuM195 administration. Patients must have recovered from the effects of previous treatment.
- Active serious infections not controlled by antibiotics.
- Pregnant women or women who are breast-feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195A single infusion of 225Ac-HuM195 will be administered at a starting dose of 0.5 μCi/kg. Additionally, 100 mCi of 213Bi-HuM195 have been administered with full dose cytarabine (200 mg/m2 daily for 5 days) without dose-limiting toxicity.Serial sampling of blood, urine, and bone marrow will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antileukemic effects. Three to six patients will be treated at each dose level. Dose escalation will proceed if less than 33% of patients in a cohort experience dose-limiting toxicity.Patients will be followed until completion of therapy as outlined in the study, loss to follow-up, death, or until the day the patient is removed from the study. | Biological | 1 |
Primary outcome
To determine the maximum tolerated dose of 225Ac-HuM195 that can be administered to patients with advanced myeloid leukemias.
Time frame: conclusion of study
2 secondary outcomes
To determine the pharmacokinetics and dosimetry of 225Ac-HuM195.
Time frame: conclusion of the study
To determine the biological effects of 225Ac-HuM195, including its ability to produce complete remissions.
Time frame: conclusion of the study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2015.
- Derived from this study: PubMed 35357290Nikitaki Z, Velalopoulou A, Zanni V, Tremi I, Havaki S, Kokkoris M, Gorgoulis VG, Koumenis C, Georgakilas AG. Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair. Expert Rev Mol Med. 2022 Mar 31;24:e15. doi: 10.1017/erm.2022.6.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dan Douer, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195 in people with Leukemia and Myelodysplastic Syndrome, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the maximum tolerated dose of 225Ac-HuM195 that can be administered to patients with advanced myeloid leukemias. (time frame: conclusion of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00672165, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2015.