Acute Myeloid LeukemiaPhase 1High RiskNCT00669890
Allogenic Stem Cell Transplantation in Patients With High Risk CD33+ AML/MDS/JMML
A Phase 1 study testing Gemtuzumab Ozogamicin, Busulfan and Cyclophosphamide in people with Acute Myeloid Leukemia and Juvenile Myelomonocytic Leukemia, run by New York Medical College at 1 site in United States.
Trial summary
The addition of gemtuzumab ozogamicin (GO) in combination with Busulfan/Cyclophosphamide followed by AlloSCT in patients with high risk CD33+ AML/JMML/MDS will be safe and well tolerated. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Acute Myeloid Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Gemtuzumab Ozogamicin, Busulfan and Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Dec 2013
- 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 Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Disease Status
- AML Induction Failure
- AML in 1st, 2nd, or 3rd Relapse (>10% bone marrow blasts)
- AML greater than or equal to 3rd CR
- MDS with >6% bone marrow blasts at diagnosis
- Secondary MDS with less than or equal to 5% bone marrow myeloblasts at diagnosis
Show all 21Show fewer
- JMML with >6% bone marrow myeloblasts at diagnosis
- Disease Immunophenotype Patients (AML only) receiving gemtuzumab ozogamicin must express minimum of >10% or =10% CD33 positivity. Patients with <10% CD33 positivity will not receive gemtuzumab ozogamicin.
- Organ Function
- Patients must have adequate organ function as defined below:
- Adequate renal function defined as:
- Serum creatinine <1.5 x normal, or
- Creatinine clearance or radioisotope GFR 40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
- Adequate liver function defined as:
- Total bilirubin 1.5 x normal, or SGOT (AST) or SGPT (ALT) <2.0 x normal or =2.0 x normal
- Adequate cardiac function defined as:
- Shortening fraction of >27% by echocardiogram, or
- Ejection fraction of >47% by radionuclide angiogram or echocardiogram
- Adequate pulmonary function defined as:
- DLCO >55% or =55% by PFT
- For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air
Who cannot join
- Patients with active CNS AML/JMML/MDS disease at time of conditioning therapy
- Female patients who are pregnant (positive HCG)
- Karnofsky <50% or Lansky <50% if 10 years or less
- Age >65 years
- Has received gemtuzumab in the previous 30 days or has not recovered from prior gemtuzumab therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Morgan Stanley Children's Hospital of NYP
New York, New York, 10032
About this study
Official title: Gemtuzumab Ozogamicin in Combination With Busulfan and Cyclophosphamid and Allogenic Stem Cell Transplantation in Patients With High Risk CD33+ Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia
The addition of gemtuzumab ozogamicin (GO) in combination with Busulfan/Cyclophosphamide followed by AlloSCT in patients with high risk CD33+ AML/JMML/MDS will be safe and well tolerated.
This study will attempt to determine the maximum tolerated dose of the immune therapy (gemtuzumab) when given in combination with the myeloablative (high dose) drugs used in this study for allogeneic stem cell transplant. (Part A)
Read the detailed description
Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of recombinant humanized anti-CD33 antibody conjugated with calicheamicin, a highly potent cytotoxic antitumor antibiotic. The antibody portion of Gemtuzumab binds specifically to the CD33 antigen, a sialic acid-dependent adhesion protein expressed on the surface of leukemia blasts, normal and leukemic myeloid colony-forming cells, including leukemic clonogenic precursors, but excluding pluripotent hematopoietic stem cells and nonhematopoietic cells. This results in formation of the complex that is internalized, upon which calicheamicin derivative is released with in the lysosomes of the myeloid cell. The free calicheamicin derivative then binds to the DNA, resulting in DNA double strand breaks and consequential cell death.
- Being tested
- Gemtuzumab Ozogamicin, Busulfan, Cyclophosphamide, Thymoglobulin, Tacrolimus
- Keywords
- AML, JMML, MDS, Allogenic Atem Cell Transplant, Gemtuzumab Ozogamicin
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Juvenile, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemtuzumab OzogamicinDrug
Also called Gemtuzumab
Dose Escalation
BusulfanDrug
Also called Busulfex
Conditioning Regimen
CyclophosphamideDrug
Also called Endoxan, Cytoxan
Conditioning Regimen
ThymoglobulinDrug
Also called ATG
(Unrelated Donors only)
TacrolimusDrug
Also called FK506
GVHD Prophylaxis
Also called MMF
GVHD Prophylaxis
MethotrexateDrug
Also called MTX
GVHD Prophylaxis
| Study group | Role | What they receive |
|---|---|---|
| study 515 | Experimental | Not described Receives: Drug: Gemtuzumab Ozogamicin; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Thymoglobulin; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerated dose or tolerable dose of Gemtuzumab Ozogamicin (anti-CD33 immunotoxin) therapy combined with Busulfan/ Cyclophosphamide in the conditioning regimen prior to AlloSCT in patients with high risk CD33+ AML/JMML/MDS
Measured: 1 year
Secondary outcomes (3)
Changes, if applicable, of minimal residual disease (cytogenetics, FISH, RT-PCR) in patients with high risk CD33+ AML/JMML/MDS after AlloSCT.
Measured: 1 year
Progression Free Survival (PFS), overall survival (OS), and disease free survival (DFS), (if applicable), following GO, Bu/CY and AlloSCT in patients with high risk CD33+ AML/JMML/MDS.
Measured: 1 year
Quality of life before and after GO, Bu/CY conditioning and AlloSCT in patients with high risk CD33+ AML/JMML/MDS
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2008 (estimated)
- Study startMay 2004
- Primary completionDec 2012
- Study completionDec 2013
Why it stopped: PI left institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York Medical College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mitchell Cairo, New York Medical College
- Investigators
- Mitchell S Cairo, MD, Study chair, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00669890
- Sponsor's protocol ID
- AAAA2533
- Other IDs
- CHNY-01-515
- Acronym
- High Risk
- Status last verified
- Apr 2015
- First submitted
- 29 Apr 2008
- Last updated
- 22 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gemtuzumab Ozogamicin in Combination With Busulfan and Cyclophosphamid and Allogenic Stem Cell Transplantation in Patients With High Risk CD33+ Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia
- ClinicalTrials.gov ID
- NCT00669890
- Acronym / sponsor ID
- High Risk / AAAA2533
- Keywords
- AML, JMML, MDS, Allogenic Atem Cell Transplant, Gemtuzumab Ozogamicin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left institution
- Enrolment
- 12 participants (actual)
- Lead sponsor
- New York Medical CollegeUniversity, hospital or other
- Study start
- May 2004
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 1 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 addition of gemtuzumab ozogamicin (GO) in combination with Busulfan/Cyclophosphamide followed by AlloSCT in patients with high risk CD33+ AML/JMML/MDS will be safe and well tolerated.
This study will attempt to determine the maximum tolerated dose of the immune therapy (gemtuzumab) when given in combination with the myeloablative (high dose) drugs used in this study for allogeneic stem cell transplant. (Part A)
Detailed description
Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of recombinant humanized anti-CD33 antibody conjugated with calicheamicin, a highly potent cytotoxic antitumor antibiotic. The antibody portion of Gemtuzumab binds specifically to the CD33 antigen, a sialic acid-dependent adhesion protein expressed on the surface of leukemia blasts, normal and leukemic myeloid colony-forming cells, including leukemic clonogenic precursors, but excluding pluripotent hematopoietic stem cells and nonhematopoietic cells. This results in formation of the complex that is internalized, upon which calicheamicin derivative is released with in the lysosomes of the myeloid cell. The free calicheamicin derivative then binds to the DNA, resulting in DNA double strand breaks and consequential cell death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| study 515 | Experimental | Drug: Gemtuzumab Ozogamicin, Drug: Busulfan, Drug: Cyclophosphamide, Drug: Thymoglobulin, Drug: Tacrolimus, Drug: Mycophenolate Mofetil, Drug: Methotrexate |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Disease Status
- AML Induction Failure
- AML in 1st, 2nd, or 3rd Relapse (>10% bone marrow blasts)
- AML greater than or equal to 3rd CR
- MDS with >6% bone marrow blasts at diagnosis
Key exclusion criteria (5 listed)
- Patients with active CNS AML/JMML/MDS disease at time of conditioning therapy
- Female patients who are pregnant (positive HCG)
- Karnofsky <50% or Lansky <50% if 10 years or less
- Age >65 years
- Has received gemtuzumab in the previous 30 days or has not recovered from prior gemtuzumab therapy.
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 |
|---|---|---|
| Gemtuzumab OzogamicinAlso: GemtuzumabDose Escalation | Drug | study 515 |
| BusulfanAlso: BusulfexConditioning Regimen | Drug | study 515 |
| CyclophosphamideAlso: Endoxan, CytoxanConditioning Regimen | Drug | study 515 |
| ThymoglobulinAlso: ATG(Unrelated Donors only) | Drug | study 515 |
| TacrolimusAlso: FK506GVHD Prophylaxis | Drug | study 515 |
| Mycophenolate MofetilAlso: MMFGVHD Prophylaxis | Drug | study 515 |
| MethotrexateAlso: MTXGVHD Prophylaxis | Drug | study 515 |
Primary outcome
Maximal tolerated dose or tolerable dose of Gemtuzumab Ozogamicin (anti-CD33 immunotoxin) therapy combined with Busulfan/ Cyclophosphamide in the conditioning regimen prior to AlloSCT in patients with high risk CD33+ AML/JMML/MDS
Time frame: 1 year
3 secondary outcomes
Changes, if applicable, of minimal residual disease (cytogenetics, FISH, RT-PCR) in patients with high risk CD33+ AML/JMML/MDS after AlloSCT.
Time frame: 1 year
Progression Free Survival (PFS), overall survival (OS), and disease free survival (DFS), (if applicable), following GO, Bu/CY and AlloSCT in patients with high risk CD33+ AML/JMML/MDS.
Time frame: 1 year
Quality of life before and after GO, Bu/CY conditioning and AlloSCT in patients with high risk CD33+ AML/JMML/MDS
Time frame: 1 year
Results and safety
The study was stopped early (reason given: PI left institution). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2015.
- (Click on "Morgan Stanley Children's Hospital" and then "Clinical Services" and then "Blood \& Marrow Transplantation")Link 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.
Mitchell S Cairo, MD study chair
Columbia University
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 Gemtuzumab Ozogamicin, Busulfan and Cyclophosphamide in people with Acute Myeloid Leukemia and Juvenile Myelomonocytic Leukemia, run by New York Medical College 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 21 inclusion and 5 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: stopped early, as of the sponsor's last update on 22 Apr 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 was stopped early (reason given: PI left institution). Results are not available in the source record.
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?
Maximal tolerated dose or tolerable dose of Gemtuzumab Ozogamicin (anti-CD33 immunotoxin) therapy combined with Busulfan/ Cyclophosphamide in the conditioning regimen prior to AlloSCT in patients with high risk CD33+ AML/JMML/MDS (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Apr 2015.