Acute Myelogenous LeukemiaPhase 1/2NCT00038831
Allo Transplantation With Mylotarg, Fludarabine and Melphalan for AML, CML and MDS
A Phase 1/2 study testing Mylotarg, Fludarabine and Melphalan in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest safe dose of Mylotarg that can be combined with chemotherapy in patients receiving allogeneic bone marrow transplantation. Read more about this study
- Who is it for?
- Ages 12 to 75 years
- Conditions the study is for
- Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Chronic Lymphocytic Leukemia
- What is being tested?
- Mylotarg, Fludarabine and Melphalan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- May 2001to Oct 2006
- Phase
- Phase 1/2
- 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 12 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients 12-75 years of age
- Patients are eligible if deemed ineligible for conventional high dose chemotherapy programs because of concurrent medical conditions. Patients with refractory AML are always eligible if ejection fraction > 35, FEV1, FVC, or DLCO > 40%, abnormal LFT's.
- Patients must have recovered from previous Grade III-IV toxicity due to prior anti-neoplastic therapy (except alopecia).
- Patients with the following disease categories will be eligible:
- AML with induction failure, relapse or 2nd remission
- MDS with IPI INT-2 or High-risk disease (Appendix 4) or CMML
Show all 14Show fewer
- CML in accelerated phase or blast crisis
- Interferon or STI resistant CML not eligible for conventional stem cell transplant
- Patients receiving prior BMT are eligible. If myeloablative chemoradiotherapy was used in the prior transplant patients must be >90 days from transplant. If non-myeloablative therapy was used patients must be >30 days post-transplant.
- Leukemia cells must express cell surface CD33 evaluated by flow cytometry in > 20% of leukemia cells.
- Patients must have an HLA-compatible related donor (6/6 or 5/6 HLA-match) capable of donating bone marrow or G-CSF stimulated peripheral blood stem cells using aphereses techniques or a 6/6 HLA matched unrelated bone marrow donor (serologic matching for Class I, molecular matching for DR?1).
- Patients must have a ECOG PS<2 (Appendix 6), Cr<2.0, bilirubin <2, and (SGPT) <3x normal
- Patients must have an estimated life expectancy > 3 months
- Patient and donor must sign informed consent. Unrelated donors will be consented according to the National Donor Marrow Registry policy
Who cannot join
- uncontrolled active infection
- HIV disease
- pregnancy and nursing
- active, uncontrolled CNS leukemia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Evaluation of Safety and Activity of Mylotarg Plus Melphalan and Fludarabine as Preparative Therapy for Older or Medically Infirm Patients Undergoing Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation
The goal of this clinical research study is to find the highest safe dose of Mylotarg that can be combined with chemotherapy in patients receiving allogeneic bone marrow transplantation. Researchers will study the effects of this treatment combination on patients with high-risk acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome.
Primary Objective:
Read more
- To determine the safety and maximum tolerated dose of Mylotarg as part of a reduced-intensity preparative regimen patients undergoing related, mismatched-related or matched unrelated donor transplantation.
Secondary Objectives:
- To evaluate response rates, engraftment kinetics and degree of chimerism achievable with this strategy.
- To evaluate the incidence and severity of GVHD in this population
- To evaluate disease-free and overall survival and relapse rates.
Read the detailed description
Before treatment starts, patients will have a complete physical exam, including blood and urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone marrow biopsy. Women who are able to have children will have a pregnancy test.
In this study, patients will receive Mylotarg twelve days before the transplant. The first patients will receive Mylotarg at the lowest dose level. As the study continues, the dose levels will be increased as long as no severe side effects occur. Mylotarg may be given in the outpatient Ambulatory Treatment Center (ATC). Patients will be monitored in the ATC for eight hours on the day of infusion. For the next 5 days, patients will be evaluated in the Clinic on a daily basis or as per physician orders. One week before the transplant, all patients will be admitted to the hospital and will continue their treatment as inpatients. Patients experiencing side effects from their leukemia or leukemia treatment may need to be hospitalized earlier.
On the 1st day of hospitalization, patients will receive fluids by vein. On the 5th, 4th, 3rd and 2nd day before the transplant, patients will receive Fludarabine, by vein. Melphalan will be given by vein on the 2nd day before transplant. Patients receiving five out of six antigen matched or unrelated bone marrow will also receive antithymocyte globulin, by vein, on the 3rd, 2nd and 1st day before transplant.
On the 7th day, healthy blood stem cells or bone marrow from the donor will be given through the central catheter. Some donor bone marrow or stem cells may be saved for future therapies.
Patients will also receive several other medications to help the treatment work and to help prevent infections while their immune system is weak. Tacrolimus and methotrexate will be given to prevent graft-versus-host disease (GVHD). GVHD occurs when the donor's immune cells fight the patient's body. The Tacrolimus will be started on the day before the transplant and will continue for up to six months. Tacrolimus is given by vein at first and then by mouth when patients are able to eat. Methotrexate is given by vein on days 1, 3, 6 and possibly on day 11 after the transplant.
Sulfamethoxazole (Bactrim) or pentamidine will be given to fight bacteria. Bactrim is given by mouth when the counts are good. Pentamidine is given by vein when the counts are low. Acyclovir will be given at first by vein and then Valtrex will be given by pill to prevent viral infections. Granulocyte colony-stimulating factor (G-CSF) will be given to help the new bone marrow grow. It is given as an injection under the skin beginning on the 7th day after the transplant. It will continue until the patient's white blood cells reach an acceptable level. Overall, some of these drugs will be given for as long as 6 months or possibly longer. Other medications may be necessary. If you are allergic to some of these drugs, changes will be made.
Patients will be in the hospital for about 3-4 weeks. Patients will have checkups every day until discharged from the hospital then 3 times a week until their blood counts improve. Patients will then be seen by their doctor at least every week until 100 days after the bone marrow transplant. Patients must stay in Houston during this time. After 100 days, patients will return at least every 3 months for the first year, then every 6 months for an additional two years.
Bone marrow samples will be taken at about 1 month, 3 months, 6 and 12 months after the transplant.
This is an investigational study. All of the drugs in this study are approved by the FDA. About 47 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Being tested
- Mylotarg, Fludarabine, Melphalan, Anti-thymocyte globulin, Stem cell transplant
- Keywords
- Acute Myelogenous leukemia, AML, Myelodysplastic Syndrome, MDS, Chronic Lymphocytic Leukemia, CML, Mylotarg, Gemtuzumab, Gemtuzumab ozogamicin, Melphalan, Alkeran, Fludarabine Phosphate, Fludarabine, Fludara, Anti-thymocyte globulin, ATG, Allogeneic Bone Marrow, Peripheral Blood Stem Cell Transplantation, Allo PBSCT, Allogeneic transplantation
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MylotargDrug
Also called Gemtuzumab, Gemtuzumab ozogamicin
Starting dose 2 mg/m^2 over 2-hour intravenous infusion on day -12.
FludarabineDrug
Also called Fludara, Fludarabine Phosphate
30 mg/m^2 will be given intravenously daily at the same time over 30 minutes on days -5, -4, -3, -2.
MelphalanDrug
Also called Alkeran
140 mg/m^2 will be given intravenously over 20 minutes starting 2 hours after the beginning of the fludarabine infusion on day -2.
Anti-thymocyte globulinDrug
Also called Rabbit anti-thymocyte globulin, Anti-thymocyte globulin (ATG)
Patients with an unrelated or mismatched related donor will receive 0.5 mg/kg on day -3 and 1.25 mg/Kg on days -2 and -1, following the chemotherapy.
Stem cell transplantProcedure or surgery
Also called alloBMT, Allo PBSCT
Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation: Infusion of blood stem cells or bone marrow cells on day 0.
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy + ATG + Stem Cell Infusion | Experimental | Not described Receives: Drug: Mylotarg; Drug: Fludarabine; Drug: Melphalan; Drug: Anti-thymocyte globulin; Procedure: Stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
Measured: Followed in outpatient clinic from day -12 (prior to transplant) thru day -6 with each dose level
Secondary outcomes (1)
Patient Response
Measured: Continously over first 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2002 (estimated)
- Study startMay 2001
- Primary completionMar 2005
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marcos De Lima, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00038831
- Sponsor's protocol ID
- ID01-010
- Status last verified
- Jul 2012
- First submitted
- 5 Jun 2002
- Last updated
- 1 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Evaluation of Safety and Activity of Mylotarg Plus Melphalan and Fludarabine as Preparative Therapy for Older or Medically Infirm Patients Undergoing Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00038831
- Acronym / sponsor ID
- ID01-010
- Keywords
- Acute Myelogenous leukemia, AML, Myelodysplastic Syndrome, MDS, Chronic Lymphocytic Leukemia, CML, Mylotarg, Gemtuzumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- May 2001
- Primary completion
- Mar 2005 (actual)
- Study completion
- Oct 2006 (actual)
- First posted
- 7 Jun 2002 (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 goal of this clinical research study is to find the highest safe dose of Mylotarg that can be combined with chemotherapy in patients receiving allogeneic bone marrow transplantation. Researchers will study the effects of this treatment combination on patients with high-risk acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome.
Primary Objective:
- To determine the safety and maximum tolerated dose of Mylotarg as part of a reduced-intensity preparative regimen patients undergoing related, mismatched-related or matched unrelated donor transplantation.
Secondary Objectives:
- To evaluate response rates, engraftment kinetics and degree of chimerism achievable with this strategy.
- To evaluate the incidence and severity of GVHD in this population
- To evaluate disease-free and overall survival and relapse rates.
Detailed description
Before treatment starts, patients will have a complete physical exam, including blood and urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone marrow biopsy. Women who are able to have children will have a pregnancy test.
In this study, patients will receive Mylotarg twelve days before the transplant. The first patients will receive Mylotarg at the lowest dose level. As the study continues, the dose levels will be increased as long as no severe side effects occur. Mylotarg may be given in the outpatient Ambulatory Treatment Center (ATC). Patients will be monitored in the ATC for eight hours on the day of infusion. For the next 5 days, patients will be evaluated in the Clinic on a daily basis or as per physician orders. One week before the transplant, all patients will be admitted to the hospital and will continue their treatment as inpatients. Patients experiencing side effects from their leukemia or leukemia treatment may need to be hospitalized earlier.
On the 1st day of hospitalization, patients will receive fluids by vein. On the 5th, 4th, 3rd and 2nd day before the transplant, patients will receive Fludarabine, by vein. Melphalan will be given by vein on the 2nd day before transplant. Patients receiving five out of six antigen matched or unrelated bone marrow will also receive antithymocyte globulin, by vein, on the 3rd, 2nd and 1st day before transplant.
On the 7th day, healthy blood stem cells or bone marrow from the donor will be given through the central catheter. Some donor bone marrow or stem cells may be saved for future therapies.
Patients will also receive several other medications to help the treatment work and to help prevent infections while their immune system is weak. Tacrolimus and methotrexate will be given to prevent graft-versus-host disease (GVHD). GVHD occurs when the donor's immune cells fight the patient's body. The Tacrolimus will be started on the day before the transplant and will continue for up to six months. Tacrolimus is given by vein at first and then by mouth when patients are able to eat. Methotrexate is given by vein on days 1, 3, 6 and possibly on day 11 after the transplant.
Sulfamethoxazole (Bactrim) or pentamidine will be given to fight bacteria. Bactrim is given by mouth when the counts are good. Pentamidine is given by vein when the counts are low. Acyclovir will be given at first by vein and then Valtrex will be given by pill to prevent viral infections. Granulocyte colony-stimulating factor (G-CSF) will be given to help the new bone marrow grow. It is given as an injection under the skin beginning on the 7th day after the transplant. It will continue until the patient's white blood cells reach an acceptable level. Overall, some of these drugs will be given for as long as 6 months or possibly longer. Other medications may be necessary. If you are allergic to some of these drugs, changes will be made.
Patients will be in the hospital for about 3-4 weeks. Patients will have checkups every day until discharged from the hospital then 3 times a week until their blood counts improve. Patients will then be seen by their doctor at least every week until 100 days after the bone marrow transplant. Patients must stay in Houston during this time. After 100 days, patients will return at least every 3 months for the first year, then every 6 months for an additional two years.
Bone marrow samples will be taken at about 1 month, 3 months, 6 and 12 months after the transplant.
This is an investigational study. All of the drugs in this study are approved by the FDA. About 47 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy + ATG + Stem Cell Infusion | Experimental | Drug: Mylotarg, Drug: Fludarabine, Drug: Melphalan, Drug: Anti-thymocyte globulin, Procedure: Stem cell transplant |
Who may qualify
- Ages
- 12 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Patients 12-75 years of age
- Patients are eligible if deemed ineligible for conventional high dose chemotherapy programs because of concurrent medical conditions. Patients with refractory AML are always eligible if ejection fraction > 35, FEV1, FVC, or DLCO > 40%, abnormal LFT's.
- Patients must have recovered from previous Grade III-IV toxicity due to prior anti-neoplastic therapy (except alopecia).
- Patients with the following disease categories will be eligible:
- Patients receiving prior BMT are eligible. If myeloablative chemoradiotherapy was used in the prior transplant patients must be >90 days from transplant. If non-myeloablative therapy was used patients must be >30 days post-transplant.
Key exclusion criteria (4 listed)
- uncontrolled active infection
- HIV disease
- pregnancy and nursing
- active, uncontrolled CNS leukemia
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 |
|---|---|---|
| MylotargAlso: Gemtuzumab, Gemtuzumab ozogamicinStarting dose 2 mg/m^2 over 2-hour intravenous infusion on day -12. | Drug | Chemotherapy + ATG + Stem Cell Infusion |
| FludarabineAlso: Fludara, Fludarabine Phosphate30 mg/m^2 will be given intravenously daily at the same time over 30 minutes on days -5, -4, -3, -2. | Drug | Chemotherapy + ATG + Stem Cell Infusion |
| MelphalanAlso: Alkeran140 mg/m^2 will be given intravenously over 20 minutes starting 2 hours after the beginning of the fludarabine infusion on day -2. | Drug | Chemotherapy + ATG + Stem Cell Infusion |
| Anti-thymocyte globulinAlso: Rabbit anti-thymocyte globulin, Anti-thymocyte globulin (ATG)Patients with an unrelated or mismatched related donor will receive 0.5 mg/kg on day -3 and 1.25 mg/Kg on days -2 and -1, following the chemotherapy. | Drug | Chemotherapy + ATG + Stem Cell Infusion |
| Stem cell transplantAlso: alloBMT, Allo PBSCTAllogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation: Infusion of blood stem cells or bone marrow cells on day 0. | Procedure or surgery | Chemotherapy + ATG + Stem Cell Infusion |
Primary outcome
Maximum Tolerated Dose (MTD) of Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
Time frame: Followed in outpatient clinic from day -12 (prior to transplant) thru day -6 with each dose level
1 secondary outcome
Patient Response
Time frame: Continously over first 30 days
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 1 Aug 2012.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
Related trials for Acute Myelogenous Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Marcos De Lima, MD principal investigator
M.D. Anderson 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 1/2 study testing Mylotarg, Fludarabine and Melphalan in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson 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 14 inclusion and 4 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 1 Aug 2012. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Maximum Tolerated Dose (MTD) of Mylotarg as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level (time frame: Followed in outpatient clinic from day -12 (prior to transplant) thru day -6 with each dose level). 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 1 Aug 2012.