AzTrials
AzTrials

Acute Myelogenous LeukemiaPhase 1AML/MDS/JMMLNCT01020539

Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia

A Phase 1 study testing Fludarabine, Busulfan and GVHD Prophylaxis in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Allogeneic stem cell transplantation (AlloSCT) followed by targeted immune therapy Gemtuzumab Ozogamicin patients with acute myeloid leukemia (AML)/juvenile myelomonocytic leukemia (JMML)/myelodysplastic syndromes (MDS) will be safe and well tolerated. Read more about this study

Who is it for?
Ages 1 month to 30 years
What is being tested?
Fludarabine, Busulfan and GVHD Prophylaxis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
11 Sep 2002to Dec 2020
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 1 month to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Disease Status
  • AML 1st complete remission (CR) with a matched family donor (excluding Downs Syndrome, acute promyelocytic leukaemia (APL), poor cytogenetics (12p, 5q, -7 and FMS-like tyrosine kinase 3 (FLT3) mutations or duplication t(9;11) and others)) and patients consented to and registered on an upfront AML COG study with a matched family donor)
  • AML 1st CR (excluding Downs Syndrome, APL, and chromosome translocation (8;21) or inversion (16) or poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication t(9;11) and others)) with unrelated donor
  • AML 2nd CR
  • Myelodysplastic Syndrome (MDS) and ≤ 5% bone marrow myeloblasts at diagnosis (de novo patients only)
  • Juvenile Myelomonocytic Leukemia (JMML) and ≤ 5% bone marrow myeloblasts at diagnosis
Show all 19Show fewer
  • In regards to disease immunophenotype, disease must express a minimum of ≥10% Cell Differential 33 (CD33) positivity for patients with AML
  • 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 glomerular filtration rate (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 2.0 x upper limit of normal (ULN), or serum glutamic-oxaloacetic transaminase (SGOT)(aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT)(alanine aminotransferase (ALT)) < 5.0 x ULN
  • Adequate cardiac function defined as:
  • Shortening fraction of ≥ 25% by echocardiogram, or
  • Ejection fraction of ≥ 45% by radionuclide angiogram or echocardiogram
  • Adequate pulmonary function defined as:
  • Diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 40% by pulmonary function tests (PFT) (Uncorrected)
  • 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 central nervous system (CNS) AML/JMML disease at time of preparative regimen
  • Secondary MDS
  • Poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication)
  • Female patients who are pregnant (positive human chorionic gonadotropin(hCG))
  • Karnofsky <70% or Lansky <50% if 10 years or less
  • Age >30 years
  • Seropositive for Human Immunodeficiency Virus (HIV)
  • Patients consented to and registered on an upfront Children's Oncology Group (COG) AML study with a matched family donor

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia (AML/MDS/JMML)

Allogeneic stem cell transplantation (AlloSCT) followed by targeted immune therapy Gemtuzumab Ozogamicin patients with acute myeloid leukemia (AML)/juvenile myelomonocytic leukemia (JMML)/myelodysplastic syndromes (MDS) will be safe and well tolerated.

Read the detailed description

Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of a 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 leukemic 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 a complex that is internalized, upon which the calicheamicin derivative is released within the lysosomes of the myeloid cell. The free calicheamicin derivative then binds to deoxyribonucleic acid (DNA), resulting in DNA double strand breaks and consequential cell death. Over 80% of AML patients possess myeloid blast cells with CD33 surface antigen expression.

Being tested
Fludarabine, Busulfan, GVHD Prophylaxis, Gemtuzumab Ozogamicin, Anti-Thymocyte Globulin
Keywords
Allogeneic Stem Cell Transplantation, Targeted Immune Therapy, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Juvenile Myelomonocytic Leukemia, AML, MDS, JMML
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Juvenile

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Fludara®

    Conditioning Regimen

  • BusulfanDrug

    Also called Busulfex®

    Conditioning Regimen

  • GVHD ProphylaxisDrug

    Can be FK506 (Tacrolimus/Prograf®), mycophenolate mofetil ((MMF)/Cellcept®), or methotrexate (MTX, amethopterin)

  • Gemtuzumab OzogamicinDrug

    Also called Mylotarg®

    Dose Escalation

  • Anti-Thymocyte GlobulinDrug

    Also called Thymoglobulin®

    Unrelated Donors only

  • IsotretinoinDrug

    Also called Accutane®, 13-cis-Retinoic Acid (cis-RA)

    JMML patients only

Study groups in NCT01020539
Study groupRoleWhat they receive
Matched Family DonorExperimentalPatients will receive a reduced intensity fludarabine (6 days)/busulfan (2 days) conditioning regimen followed by a stem cell transplant from a related family donor using bone marrow or cord blood stem cells. Then followed by Gemtuzumab Ozogamicin, once at about 2-6 months post alloSCT and once at least 2 months after the first dose. Patients with JMML will also receive cis-retinoic acid (Isotretinoin). During and following transplantation patients will receive methylprednisolone for immune suppression. Graft-versus-host-disease (GVHD) prophylaxis will consist of tacrolimus, mycophenolate mofetil and additionally methotrexate in recipients of unrelated adult transplants.
Receives: Drug: Fludarabine; Drug: Busulfan; Drug: GVHD Prophylaxis; Drug: Gemtuzumab Ozogamicin
Unrelated DonorExperimentalPatients will receive a reduced intensity fludarabine (6 days)/busulfan (2 days) conditioning regimen followed by a stem cell transplant from an unrelated donor using matched bone marrow or cord blood stem cells.Then followed by Gemtuzumab Ozogamicin, once at about 2-6 months post alloSCT and once at least 2 months after the first dose. Patients with JMML will also receive cis-retinoic acid (Isotretinoin). During and following transplantation patients will receive methylprednisolone for immune suppression and unrelated donor transplant recipients will additionally receive Anti-Thymocyte Globulin. GVHD prophylaxis will consist of tacrolimus, mycophenolate mofetil and additionally methotrexate in recipients of unrelated adult transplants.
Receives: Drug: Anti-Thymocyte Globulin; Drug: Isotretinoin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO)

    To determine the maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) (anti CD33 immunotoxin) therapy following reduced intensity (RI) allogeneic stem cell transplantation (alloSCT) in patients with average risk AML/JMML/MDS.

    Measured: Up to 2 years

Secondary outcomes (5)

  1. Change of minimal residual disease

    To measure the changes, if applicable, of minimal residual disease prior to and after consolidation therapy with targeted immunotherapy in average risk AML/JMML/MDS post RI AlloSCT.

    Measured: Day 60, Day 100, Day 180, 1 year, 2 years

  2. Incidence of minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue

    To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the incidence of development of MHA specific cytotoxic T-lymphocytes (CTLs).

    Measured: Up to 2 years

  3. Degree of mixed/complete donor chimerism

    To determine the degree of mixed/complete donor chimerism after RI AlloSCT in patients with average risk AML/JMML/MDS.

    Measured: Up to 2 years

  4. Event free survival (EFS) rate

    To determine event free survival (EFS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.

    Measured: Up to 2 years

  5. Overall survival (OS) rate

    To determine overall survival (OS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2009 (estimated)
  2. Study start11 Sep 2002
  3. Primary completion20 Jul 2011
  4. Study completionDec 2020

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01020539
Sponsor's protocol ID
AAAA6378
Other IDs
CHNY-504
Acronym
AML/MDS/JMML
Status last verified
Aug 2021
First submitted
23 Nov 2009
Last updated
6 Aug 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fludarabine, Busulfan and GVHD Prophylaxis in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by Columbia University 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 19 inclusion and 8 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 6 Aug 2021. 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?

Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) (time frame: Up to 2 years). 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 NCT01020539.

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 6 Aug 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in