Leukemia, MyeloidPhase 3NCT00568633
Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
A Phase 3 study testing Allogeneic HSCT, Anti-thymocyte globulin (ATG) and Cyclosporine (CSP) in people with Leukemia, Myeloid and Leukemia, run by Stanford University at 5 sites in United States.
Trial summary
Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Leukemia, Myeloid, Leukemia, Acute Myeloid Leukemia (AML)
- What is being tested?
- Allogeneic HSCT, Anti-thymocyte globulin (ATG) and Cyclosporine (CSP)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 5 sitesUnited States
- Study dates
- Aug 2007to 31 Dec 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 50 years of age and ≤ 75 years of age.
- De novo acute myelogenous leukemia (AML), based on FAB and WHO criteria.
- Intermediate or unfavorable cytogenetic abnormalities based on Southwest Oncology Group (SWOG) Cytogenetic Criteria.
- First morphologic complete remission (CR), or CRp (a complete remission but with low platelets) following 1 or 2 courses of induction therapy, documented no more than 8 weeks prior to the date of enrollment and confirmed at time of enrollment.
- Karnofsky Performance Score ≥ 60.
- Suitable for non-myeloablative transplantation or best treatment.
- Able to understand and willing to sign a written informed consent document.
Who cannot join
- AML with favorable cytogenetic features based on SWOG Cytogenetic Criteria
- AML, either treatment-related or MDS-related
- Active CNS disease as identified by positive CSF cytospin at time of enrollment.
- Prior or concurrent malignancies except localized non-melanoma skin malignancies or treated cervical carcinoma in situ. (EXCEPTION: Cancer treated with curative intent > 5 years previously is allowed. EXCEPTION: Low grade lymphoma is allowed as long as active treatment is not required for control of disease)
- Planned for allogeneic transplant using a full-dose conditioning
- Life expectancy < 1 year due to diseases other than malignancy
Show all 21Show fewer
- Pregnant or breastfeeding.
- HIV-seropositive.
- Uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month.
- Symptomatic coronary artery disease or uncontrolled congestive heart failure. Left ventricular ejection fraction (LVEF) is not required to be measured, however if measured, exclusion if ejection fraction is < 30%.
- Requiring supplementary continuous oxygen. Diffusing capacity of the lungs for carbon monoxide (DLCO) is not required to be measured, however if it is measured, exclusion if DLCO < 35%.
- Fulminant liver failure
- Cirrhosis with evidence of portal hypertension or bridging fibrosis
- Alcoholic hepatitis
- Esophageal varices
- A history of bleeding esophageal varices
- Hepatic encephalopathy
- Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time
- Ascites related to portal hypertension
- Chronic viral hepatitis with total serum bilirubin > 3 mg/dL
- Symptomatic biliary disease
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Kaiser Permanente Northern California
Hayward, California, 94545
Cedars-Sinai Medical Center
Los Angeles, California, 90048
West Virginia University Hospital
Morgantown, West Virginia, 26506
Univeristy of California Davis Medical Center
Sacramento, California, 95817
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: A California Cooperative Clinical Study Comparing Allogeneic Hematopoietic Cell Transplantation Using Nonmyeloablative Host Conditioning With Total Lymphoid Irradiation and Anti-thymocyte Globulin Versus Best Standard of Care in Acute Myeloid Leukemia (AML) in First Complete Remission
Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Bone marrow transplantation from a sibling donor may improve cure rates; however, patients over 50 years of age have a high risk of complications and therefore generally are excluded from this treatment option. Recently our group developed a transplantation strategy for older cancer patients that protects against transplant-associated complications, yet does not interfere with the ability of the transplanted donor cells to destroy cancer cells. With this new method, we can now safely evaluate transplantation as a curative therapy for AML patients over the age of 50. We have assembled clinical and scientific researchers throughout the state of California to study and compare bone marrow transplantation using our new approach with the best standard of care chemotherapy in AML patients over the age of 50. The results of this study have the potential to establish a new treatment standard that will improve survival of older AML patients.
- Conditions
- Leukemia, Myeloid, Leukemia, Acute Myeloid Leukemia (AML)
- Being tested
- Allogeneic HSCT, Anti-thymocyte globulin (ATG), Cyclosporine (CSP), Mycophenolate mofetil (MMF), Total lymphoid irradiation (TLI)
- Medical subject headings
- Leukemia, Myeloid, Leukemia, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic HSCTProcedure or surgery
Also called Hematopoietic stem cell transplantation (HSCT), Peripheral blood stem cell (PBSC) transplantation
Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg.
Anti-thymocyte globulin (ATG)Drug
Also called Thymoglobulin, Anti-thymocyte globulin (rabbit) (ATG)
1.5 mg/kg for 5 days by IV
Cyclosporine (CSP)Drug
Also called Ciclosporin, cyclosporin A, cyclosporin
6.25 mg/kg twice daily oral
Mycophenolate mofetil (MMF)Drug
Also called Cellcept
15 mg/kg twice daily oral
Total lymphoid irradiation (TLI)Radiation
80 cGy/fraction radiotherapy in 10 fractions.
Methylprednisolone sodium succinateDrug
Also called Solumedrol, Medrol, Depo-Medrol, P-Care D40
1.0 mg/kg for 5 days by IV
Best standard careDrug
Also called Standard of Care (physician discretion), Regular medical care
Intervention consist of:
- Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation)
- Autologous transplantation
- Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning
- Umbilical cord blood transplantation
- Haploidentical transplantation
| Study group | Role | What they receive |
|---|---|---|
| Allo-HSCT + TLI + ATG | Experimental | Participants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive:
* Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1)
* Anti-thymocyte globulin (ATG) Days -11 to -7
* Methylprednisolone Days -11 to -7
* Cyclosporine (CSP) Days -4 to +2
* 5+ of 6 HLA-matched CD34+ cells on Day 0
* Mycophenolate mofetil (MMF), Day 0 to Day +28 Receives: Procedure: Allogeneic HSCT; Drug: Anti-thymocyte globulin (ATG); Drug: Cyclosporine (CSP); Drug: Mycophenolate mofetil (MMF); Radiation: Total lymphoid irradiation (TLI); Drug: Methylprednisolone sodium succinate |
| Best Standard Care | Active comparator | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of:
* Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation)
* Autologous transplantation
* Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning
* Umbilical cord blood transplantation
* Haploidentical transplantation Receives: Drug: Best standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall survival defined as the time interval between the date of attaining a first complete remission (CR) and the date of death from any cause. The outcome is reported as the number of participants alive (without dispersion).
Measured: 2 years
Secondary outcomes (7)
Disease-free Survival (DFS)
Disease-free survival is defined as the time interval between the date of attaining a first complete remission (CR) and the date of relapse. Disease free survival (DFS) will compared to conventional therapy vs Non-myeloablative Host Conditioning (NMA HCT). The outcome is reported as the number of participants which never experienced disease relapse (without dispersion).
Measured: 2 years
Non-relapse Mortality
Non-relapse mortality is defined as death that occurs after therapy, from any cause except a cause associated with relapse. This will be reported as the number of participants experiencing non-relapse mortality (a number without dispersion).
Measured: 2 years
Relapse Rate
Relapse will be determined as ≥ 5% blast cells in the bone marrow, not secondary to regeneration after myelosuppressive therapy; OR emergence of extramedullary leukemia; OR the re-emergence of blasts in the peripheral blood. The outcome will be reported as the number and percentage of participants that meet these criteria (a number without dispersion).
Measured: 2 years
Transplant-related Mortality
Transplant-related mortality will be assessed as any death occurring within 6 months post-transplant, from any cause except relapse. It will be measured at 100 day and 6 months after transplant. The outcome is expressed as at the number of participants experiencing transplant-related mortality (a number without dispersion).
Measured: 100 days and 6 months
Complete Donor Hematopoietic Cell Chimerism
Complete donor hematopoietic cell chimerism was evaluated in transplant recipients. Complete donor chimerism will be assessed as the presence of > 95% donor T-cells (CD3+) in the blood. The outcome is reported as the percentage of participants that achieve complete donor chimerism, a number without dispersion.
Measured: 2 years
Early Graft Loss
Early graft loss means a failure to achieve donor T-cell chimerism of > 5% at any time after transplant. The outcome is reported as the percentage of participants that experience early graft loss, a number without dispersion.
Measured: 2 years
Patients Completing the Intended Therapy in Both Arms
The assessment for completion of the intended therapy (in both arms) will be reported as the percentage of participants, a number without dispersion
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2007 (estimated)
- Study startAug 2007
- Primary completion31 Dec 2015
- Study completion31 Dec 2015
Why it stopped: Poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, MyeloidStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Treatment assignment was based on availability of an HLA-matched donor.
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Principal investigator, Robert Lowsky, Stanford University
- Investigators
- Robert Lowsky, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00568633
- Sponsor's protocol ID
- IRB-05567
- Other IDs
- 97843, BMT190
- Status last verified
- Aug 2019
- First submitted
- 4 Dec 2007
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A California Cooperative Clinical Study Comparing Allogeneic Hematopoietic Cell Transplantation Using Nonmyeloablative Host Conditioning With Total Lymphoid Irradiation and Anti-thymocyte Globulin Versus Best Standard of Care in Acute Myeloid Leukemia (AML) in First Complete Remission
- ClinicalTrials.gov ID
- NCT00568633
- Acronym / sponsor ID
- IRB-05567
- Conditions
- Leukemia, Myeloid, Leukemia, Acute Myeloid Leukemia (AML)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Aug 2007 (actual)
- Primary completion
- 31 Dec 2015 (actual)
- Study completion
- 31 Dec 2015 (actual)
- First posted
- 6 Dec 2007 (estimated)
- Results
- Posted 11 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Bone marrow transplantation from a sibling donor may improve cure rates; however, patients over 50 years of age have a high risk of complications and therefore generally are excluded from this treatment option. Recently our group developed a transplantation strategy for older cancer patients that protects against transplant-associated complications, yet does not interfere with the ability of the transplanted donor cells to destroy cancer cells. With this new method, we can now safely evaluate transplantation as a curative therapy for AML patients over the age of 50. We have assembled clinical and scientific researchers throughout the state of California to study and compare bone marrow transplantation using our new approach with the best standard of care chemotherapy in AML patients over the age of 50. The results of this study have the potential to establish a new treatment standard that will improve survival of older AML patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Treatment assignment was based on availability of an HLA-matched donor.
| Arm | Type | Receives |
|---|---|---|
| Allo-HSCT + TLI + ATG | Experimental | Procedure: Allogeneic HSCT, Drug: Anti-thymocyte globulin (ATG), Drug: Cyclosporine (CSP), Drug: Mycophenolate mofetil (MMF), Radiation: Total lymphoid irradiation (TLI), Drug: Methylprednisolone sodium succinateParticipants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: * Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) * Anti-thymocyte globulin (ATG) Days -11 to -7 * Methylprednisolone Days -11 to -7 * Cyclosporine (CSP) Days -4 to +2 * 5+ of 6 HLA-matched CD34+ cells on Day 0 * Mycophenolate mofetil (MMF), Day 0 to Day +28 |
| Best Standard Care | Active comparator | Drug: Best standard careRegular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: * Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) * Autologous transplantation * Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning * Umbilical cord blood transplantation * Haploidentical transplantation |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥ 50 years of age and ≤ 75 years of age.
- De novo acute myelogenous leukemia (AML), based on FAB and WHO criteria.
- Intermediate or unfavorable cytogenetic abnormalities based on Southwest Oncology Group (SWOG) Cytogenetic Criteria.
- First morphologic complete remission (CR), or CRp (a complete remission but with low platelets) following 1 or 2 courses of induction therapy, documented no more than 8 weeks prior to the date of enrollment and confirmed at time of enrollment.
- Karnofsky Performance Score ≥ 60.
Key exclusion criteria (21 listed)
- AML with favorable cytogenetic features based on SWOG Cytogenetic Criteria
- AML, either treatment-related or MDS-related
- Active CNS disease as identified by positive CSF cytospin at time of enrollment.
- Prior or concurrent malignancies except localized non-melanoma skin malignancies or treated cervical carcinoma in situ. (EXCEPTION: Cancer treated with curative intent > 5 years previously is allowed. EXCEPTION: Low grade lymphoma is allowed as long as active treatment is not required for control of disease)
- Planned for allogeneic transplant using a full-dose conditioning
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 |
|---|---|---|
| Allogeneic HSCTAlso: Hematopoietic stem cell transplantation (HSCT), Peripheral blood stem cell (PBSC) transplantationAllogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. | Procedure or surgery | Allo-HSCT + TLI + ATG |
| Anti-thymocyte globulin (ATG)Also: Thymoglobulin, Anti-thymocyte globulin (rabbit) (ATG)1.5 mg/kg for 5 days by IV | Drug | Allo-HSCT + TLI + ATG |
| Cyclosporine (CSP)Also: Ciclosporin, cyclosporin A, cyclosporin6.25 mg/kg twice daily oral | Drug | Allo-HSCT + TLI + ATG |
| Mycophenolate mofetil (MMF)Also: Cellcept15 mg/kg twice daily oral | Drug | Allo-HSCT + TLI + ATG |
| Total lymphoid irradiation (TLI)80 cGy/fraction radiotherapy in 10 fractions. | Radiation | Allo-HSCT + TLI + ATG |
| Methylprednisolone sodium succinateAlso: Solumedrol, Medrol, Depo-Medrol, P-Care D401.0 mg/kg for 5 days by IV | Drug | Allo-HSCT + TLI + ATG |
| Best standard careAlso: Standard of Care (physician discretion), Regular medical careIntervention consist of: * Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) * Autologous transplantation * Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning * Umbilical cord blood transplantation * Haploidentical transplantation | Drug | Best Standard Care |
Primary outcome
Overall Survival (OS)
Time frame: 2 years
Overall survival defined as the time interval between the date of attaining a first complete remission (CR) and the date of death from any cause. The outcome is reported as the number of participants alive (without dispersion).
7 secondary outcomes
Disease-free Survival (DFS)
Time frame: 2 years
Non-relapse Mortality
Time frame: 2 years
Relapse Rate
Time frame: 2 years
Transplant-related Mortality
Time frame: 100 days and 6 months
Complete Donor Hematopoietic Cell Chimerism
Time frame: 2 years
Early Graft Loss
Time frame: 2 years
Patients Completing the Intended Therapy in Both Arms
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Robert Lowsky principal investigator
Stanford University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Allogeneic HSCT, Anti-thymocyte globulin (ATG) and Cyclosporine (CSP) in people with Leukemia, Myeloid and Leukemia, run by Stanford University at 5 sites 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 7 inclusion and 21 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 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Survival (OS) (time frame: 2 years). 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 24 Sep 2019.