LeukemiaPhase 2NCT00499889
Imatinib Mesylate, Busulfan, Fludarabine, and Antithymocyte Globulin for CML Patients
A Phase 2 study testing Imatinib Mesylate, Fludarabine (Fludara) and Busulfan in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary Objective: To estimate the probability of molecular complete remission at one year for the described sequential treatment approach, with nonablative hematopoietic transplantation, post transplant imatinib mesylate and donor lymphocyte infusion, in patients with Ph-positive Chronic Myelogenous Leukemia (CML)… Read more about this study
- Who is it for?
- Ages Up to 70 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Imatinib Mesylate, Fludarabine (Fludara) and Busulfan
- 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
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2003to Nov 2009
- Phase
- Phase 2
- 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 Up to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of Ph+ chronic myelogenous leukemia (CML) in first chronic phase without a complete hematologic response after 3 months of Imatinib mesylate therapy, or >=35% Ph+ cells despite > 6 months of Imatinib mesylate treatment, or after disease progression from a complete or partial response. Any patient with accelerated phase or blast crisis who achieves a subsequent chronic phase is eligible. Patients must have an HLA matched related or unrelated donor or one antigen mismatched related donor.
- Patients should be less than 70 years of age. Patients less than 30 years of age who achieve a hematologic remission with imatinib therapy are eligible regardless of cytogenetic response.
- Patients are stratified as Group 1: First chronic phase, Group 2 Accelerated phase or blast crisis that achieved a hematologic remission with imatinib mesylate-based treatment.
Who cannot join
- Zubrod Performance Scale (PS) >=2, uncontrolled infection, Creatinine > 2.0 mg/dl; Ejection fraction < 40%; Carbon Monoxide Diffusing Capacity (DLCO) < 45% of predicted; Serum bilirubin > 2 gm/dl; GPT (Glutamic-pyruvic transaminase) or GOT (glutamic-oxaloacetic transaminase)> 3 times normal values. Patients should not be human immunodeficiency virus (HIV) seropositive or pregnant.
- Patients should not have progressed to accelerated phase or blast crisis while receiving imatinib mesylate containing therapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Imatinib Mesylate, Busulfan, Fludarabine, Antithymocyte Globulin and Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia
Primary Objective:
To estimate the probability of molecular complete remission at one year for the described sequential treatment approach, with nonablative hematopoietic transplantation, post transplant imatinib mesylate and donor lymphocyte infusion, in patients with Ph-positive Chronic Myelogenous Leukemia (CML) not in blastic transformation.
Secondary Objective:
Response to post transplant Imatinib mesylate therapy for 12 weeks as treatment of residual disease, response to donor lymphocyte infusion (DLI) for residual disease following imatinib mesylate therapy, as well as engraftment, toxicity, disease free survival and survival, effect of busulfan pharmacokinetics on study outcome.
Read the detailed description
Patients will have blood and bone marrow tests performed as well as chest and sinus X-rays and tests of their heart and lung function. Approximately 5 tablespoons of blood will be drawn.
All patients in this study will receive imatinib mesylate by mouth for 9 days, unless the patient is known to be allergic or have symptomatic intolerance to the drug, or if the leukemia has failed to respond to imatinib. Fludarabine 40 mg/m2 by vein for 4 days (days -5 to -2), busulfan 130 mg/m2 by vein for 2 days (days -3 and -2), and ATG (Antithymocyte Globulin) 2.5 mg/kg by vein for 3 days (-3,-2 and -1).
Patients will then receive the donor bone marrow or blood stem cells by vein over approximately one hour on day 0.
After the infusion of the donor cells, you will receive immunosuppressive therapy with tacrolimus and methotrexate to decrease the risk of developing graft-vs-host disease (GvHD).
Patients will need frequent blood tests to monitor their counts and blood chemistries. This is generally done daily while in hospital and at least twice per week for the first 100 days post transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to evaluate response to treatment; Blood and bone marrow exams are to be performed at one, two three, six, 12 and 18 months post transplant and yearly thereafter for 5 years. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.
Patients in whom treatment produces a remission, in which no sign of the leukemia can be detected, will receive no further therapy unless the leukemia recurs. Patients with evidence of leukemia after 3 months from the transplant will receive additional treatment with imatinib mesylate; those with detectable leukemia after an additional 3 months may receive an infusion of immune cells from the transplant donor.
If there is evidence of leukemia after the transplant, you will receive additional treatment with imatinib mesylate. If leukemia cells can still be detected, additional donor immune cells will be given to you by vein.
Patients are considered on the study for 5 years after the transplant.
A total of 90 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Leukemia
- Being tested
- Imatinib Mesylate, Fludarabine (Fludara), Busulfan, Antithymocyte Globulin (ATG), Tacrolimus
- Keywords
- Chronic Myelogenous Leukemia, Allogeneic Stem Cell Transplantation, Leukemia, Imatinib Mesylate, Gleevec, Busulfan, Busulfex, Myleran, Fludarabine, ATG, STI571, Antithymocyte Globulin, Thymoglobulin
- Medical subject headings
- Leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib MesylateDrug
Also called Gleevec, STI571
400 mg by mouth twice daily for 9 Days
Fludarabine (Fludara)Drug
Also called Fludarabine Phosphate, Fludara, Fludarabine
40 mg/m^2 by vein daily for 4 Days
BusulfanDrug
Also called Busulfex, Myleran
130 mg/m^2 by vein daily for 2 Days
Antithymocyte Globulin (ATG)Drug
Also called ATG, Thymoglobulin
2.5 mg/kg by vein daily for 3 Days
TacrolimusDrug
Also called Prograf
Tacrolimus levels maintained between 5-15 ng/dl, first as continuous IV infusion, and converted to oral every 12 hour dosing as tolerated. Starting day -2 until day 180.
MethotrexateDrug
5 mg/m2 on days 1, 3, 6 and 11.
Donor lymphocyte infusion (DLI)Procedure or surgery
Also called buffy coat fusion, donor leukocyte infusion, apheresis, donor immune cell infusion
Infusion of lymphocytes from the original bone marrow donor by vein if relapse after >4 weeks of imatinib.
Stem Cell TransplantProcedure or surgery
Also called stem cell infusion, stem cell transplantation, ALLOGENEIC STEM CELL TRANSPLANTATION, HSCT
Infusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0.
| Study group | Role | What they receive |
|---|---|---|
| Imatinib, Busulfan, Fludara + Antithymocyte Globulin | Experimental | Oral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease. Receives: Drug: Imatinib Mesylate; Drug: Fludarabine (Fludara); Drug: Busulfan; Drug: Antithymocyte Globulin (ATG); Drug: Tacrolimus; Drug: Methotrexate; Procedure: Donor lymphocyte infusion (DLI); Procedure: Stem Cell Transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants in Complete Molecular Remission at 1 Year
Participants at 1 year in molecular remission, post transplant, post imatinib mesylate and donor lymphocyte infusion (DLI). Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests (this test is most commonly used in clinical trials).
Measured: Baseline to 1 year
Secondary outcomes (2)
Participants' With mCR Response to Post Transplant Imatinib Mesylate Therapy
Number of participants with response of molecular complete remission (mCR) to Imatinib Mesylate therapy as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.
Measured: 1 Year
Participants' With mCR Response to Post Transplant DLI
Number of participants with response of molecular complete remission (mCR) to DLI as treatment for residual disease after transplant. Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests.
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 posted12 Jul 2007 (estimated)
- Study startFeb 2003
- Primary completionNov 2009
- Study completionNov 2009
Why it stopped: Support issue.
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 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Richard E. Champlin, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499889
- Sponsor's protocol ID
- ID02-901
- Status last verified
- Apr 2012
- First submitted
- 10 Jul 2007
- Last updated
- 23 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imatinib Mesylate, Busulfan, Fludarabine, Antithymocyte Globulin and Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT00499889
- Acronym / sponsor ID
- ID02-901
- Conditions
- Leukemia
- Keywords
- Chronic Myelogenous Leukemia, Allogeneic Stem Cell Transplantation, Leukemia, Imatinib Mesylate, Gleevec, Busulfan, Busulfex, Myleran
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Support issue.
- Enrolment
- 42 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2003
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 12 Jul 2007 (estimated)
- Results
- Posted 7 Nov 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To estimate the probability of molecular complete remission at one year for the described sequential treatment approach, with nonablative hematopoietic transplantation, post transplant imatinib mesylate and donor lymphocyte infusion, in patients with Ph-positive Chronic Myelogenous Leukemia (CML) not in blastic transformation.
Secondary Objective:
Response to post transplant Imatinib mesylate therapy for 12 weeks as treatment of residual disease, response to donor lymphocyte infusion (DLI) for residual disease following imatinib mesylate therapy, as well as engraftment, toxicity, disease free survival and survival, effect of busulfan pharmacokinetics on study outcome.
Detailed description
Patients will have blood and bone marrow tests performed as well as chest and sinus X-rays and tests of their heart and lung function. Approximately 5 tablespoons of blood will be drawn.
All patients in this study will receive imatinib mesylate by mouth for 9 days, unless the patient is known to be allergic or have symptomatic intolerance to the drug, or if the leukemia has failed to respond to imatinib. Fludarabine 40 mg/m2 by vein for 4 days (days -5 to -2), busulfan 130 mg/m2 by vein for 2 days (days -3 and -2), and ATG (Antithymocyte Globulin) 2.5 mg/kg by vein for 3 days (-3,-2 and -1).
Patients will then receive the donor bone marrow or blood stem cells by vein over approximately one hour on day 0.
After the infusion of the donor cells, you will receive immunosuppressive therapy with tacrolimus and methotrexate to decrease the risk of developing graft-vs-host disease (GvHD).
Patients will need frequent blood tests to monitor their counts and blood chemistries. This is generally done daily while in hospital and at least twice per week for the first 100 days post transplant. You may need frequent blood transfusions and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to evaluate response to treatment; Blood and bone marrow exams are to be performed at one, two three, six, 12 and 18 months post transplant and yearly thereafter for 5 years. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.
Patients in whom treatment produces a remission, in which no sign of the leukemia can be detected, will receive no further therapy unless the leukemia recurs. Patients with evidence of leukemia after 3 months from the transplant will receive additional treatment with imatinib mesylate; those with detectable leukemia after an additional 3 months may receive an infusion of immune cells from the transplant donor.
If there is evidence of leukemia after the transplant, you will receive additional treatment with imatinib mesylate. If leukemia cells can still be detected, additional donor immune cells will be given to you by vein.
Patients are considered on the study for 5 years after the transplant.
A total of 90 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib, Busulfan, Fludara + Antithymocyte Globulin | Experimental | Drug: Imatinib Mesylate, Drug: Fludarabine (Fludara), Drug: Busulfan, Drug: Antithymocyte Globulin (ATG), Drug: Tacrolimus, Drug: Methotrexate, Procedure: Donor lymphocyte infusion (DLI), Procedure: Stem Cell TransplantOral Imatinib Mesylate 400 mg twice a day for 9 Days; Busulfan 130 mg/m^2 by vein (IV) daily for 2 Days; Fludara 40 mg/m^2 IV daily for 4 Days; Antithymocyte Globulin (ATG) 2.5 mg/kg IV daily for 3 Days; Tacrolimus levels maintained between 5-15 ng/dl, Day -2 to Day 180; Methotrexate 5 mg/m2 on days 1, 3, 6 and 11; and Donor bone marrow or blood stem cells infused on day 0 with possible donor lymphocyte infusion (DLI) for progressive disease. |
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of Ph+ chronic myelogenous leukemia (CML) in first chronic phase without a complete hematologic response after 3 months of Imatinib mesylate therapy, or >=35% Ph+ cells despite > 6 months of Imatinib mesylate treatment, or after disease progression from a complete or partial response. Any patient with accelerated phase or blast crisis who achieves a subsequent chronic phase is eligible. Patients must have an HLA matched related or unrelated donor or one antigen mismatched related donor.
- Patients should be less than 70 years of age. Patients less than 30 years of age who achieve a hematologic remission with imatinib therapy are eligible regardless of cytogenetic response.
- Patients are stratified as Group 1: First chronic phase, Group 2 Accelerated phase or blast crisis that achieved a hematologic remission with imatinib mesylate-based treatment.
Key exclusion criteria (2 listed)
- Zubrod Performance Scale (PS) >=2, uncontrolled infection, Creatinine > 2.0 mg/dl; Ejection fraction < 40%; Carbon Monoxide Diffusing Capacity (DLCO) < 45% of predicted; Serum bilirubin > 2 gm/dl; GPT (Glutamic-pyruvic transaminase) or GOT (glutamic-oxaloacetic transaminase)> 3 times normal values. Patients should not be human immunodeficiency virus (HIV) seropositive or pregnant.
- Patients should not have progressed to accelerated phase or blast crisis while receiving imatinib mesylate containing 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 |
|---|---|---|
| Imatinib MesylateAlso: Gleevec, STI571400 mg by mouth twice daily for 9 Days | Drug | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
| Fludarabine (Fludara)Also: Fludarabine Phosphate, Fludara, Fludarabine40 mg/m^2 by vein daily for 4 Days | Drug | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
| BusulfanAlso: Busulfex, Myleran130 mg/m^2 by vein daily for 2 Days | Drug | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
| Antithymocyte Globulin (ATG)Also: ATG, Thymoglobulin2.5 mg/kg by vein daily for 3 Days | Drug | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
| TacrolimusAlso: PrografTacrolimus levels maintained between 5-15 ng/dl, first as continuous IV infusion, and converted to oral every 12 hour dosing as tolerated. Starting day -2 until day 180. | Drug | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
| Methotrexate5 mg/m2 on days 1, 3, 6 and 11. | Drug | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
| Donor lymphocyte infusion (DLI)Also: buffy coat fusion, donor leukocyte infusion, apheresis, donor immune cell infusionInfusion of lymphocytes from the original bone marrow donor by vein if relapse after >4 weeks of imatinib. | Procedure or surgery | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
| Stem Cell TransplantAlso: stem cell infusion, stem cell transplantation, ALLOGENEIC STEM CELL TRANSPLANTATION, HSCTInfusion of donor bone marrow or blood stem cells by vein over approximately one hour on day 0. | Procedure or surgery | Imatinib, Busulfan, Fludara + Antithymocyte Globulin |
Primary outcome
Number of Participants in Complete Molecular Remission at 1 Year
Time frame: Baseline to 1 year
Participants at 1 year in molecular remission, post transplant, post imatinib mesylate and donor lymphocyte infusion (DLI). Molecular remission is a complete remission with no evidence of disease in the blood cells and/or bone marrow using sensitive polymerase chain reaction (PCR) tests (this test is most commonly used in clinical trials).
2 secondary outcomes
Participants' With mCR Response to Post Transplant Imatinib Mesylate Therapy
Time frame: 1 Year
Participants' With mCR Response to Post Transplant DLI
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The University of Texas M.D.Anderson Cancer CenterLink provided by the sponsor.
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous 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
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.
Richard E. Champlin, 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 2 study testing Imatinib Mesylate, Fludarabine (Fludara) and Busulfan in people with Leukemia, 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 3 inclusion and 2 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 23 Apr 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 7 Nov 2011). 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?
Number of Participants in Complete Molecular Remission at 1 Year (time frame: Baseline to 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 23 Apr 2012.