Acute Myelogenous LeukemiaPhase 1/2NCT00043810
Study of Gelonin Purging of Autologous Stem Cells for Transplantation
A Phase 1/2 study testing Gelonin, Busulfan and Fludarabine in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Patients with Acute Myelogenous Leukemia or Myelodysplastic are able to achieve a complete remission but fail to achieve a prolonged disease-free survival. High dose chemotherapy and autologous bone marrow transplantation has been shown to be effective in this group of patients but hematopoietic recovery is slow, and… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Myelogenous Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Gelonin, Busulfan and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2002to Mar 2005
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with AML, RAEB-t, RAEB, or CMML who are in first remission and have poor prognosis cytogenetic abnormalities (i.e: deletions of chromosome 5, 7, 20; trisomy 8, t9,22,11q23 abnormalities or complex karyotypes).*
- Patients with AML, RAEB-t, RAEB, or CMML who are in second or subsequent remission.
- Remission is defined as ANC>1.5 x 109/Lt; Platelet count >100 x 109/Lt, and red cell transfusion independence.
- Male or female who have provided written informed consent.
- Tumor cells must be > 80 % CD-33 positive by flow cytometry.
- For women of childbearing potential (i.e., exclude post-menopausal women, women who have been surgically sterilized), adequate birth control methods must be used. Acceptable birth control methods are limited to oral contraceptives, implants, diaphragm, IUD or spermicide used with a condom)
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- No chemotherapy for the two weeks prior to entering the study.
- No evidence of residual toxic effects from prior chemotherapy.
- Patients with proven bacterial infection are not eligible until resolution of the infection (patient afebrile, not on steroids). Patients with active fungal infections are eligible only if evidence of response to antifungal medications is documented and they do not have fever exceeding 38C.
- Must have at least 5 x 106 CD34+ peripheral blood stem cells collected.
- All patients who have had less than 7 x 106 CD34+ cells/kg collected, should have a bone marrow harvest to serve as back-up.
- A minimum of 1 x 106 CD34+ cells/kg of unpurged bone marrow or 2 x 106 CD34+ cells/kg of unpurged peripheral blood need to be stored as backup to be eligible for this protocol.
- Patients must have bilirubin less than 2.0, transaminases less than 4 x upper limit of normal.
- Pulmonary function tests >50% predicted for DLCO, FVC and FEV1
- No active uncontrolled infection
- No active CNS disease
- No uncontrolled arrythmias
- Zubrod Performance Status less than or equal to 2
Who cannot join
- Active CNS disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dose Finding Study of Gelonin Purging of Autologous Stem Cells for Transplantation of Patients With AML/MDS in First or Subsequent Remission
Patients with Acute Myelogenous Leukemia or Myelodysplastic are able to achieve a complete remission but fail to achieve a prolonged disease-free survival. High dose chemotherapy and autologous bone marrow transplantation has been shown to be effective in this group of patients but hematopoietic recovery is slow, and infectious or bleeding complications are common. The delay in hematopoietic recover is accentuated by the use of purging techniques. This is a novel purging approach for autologous stem cell transplantation in patients with Acute Myelogenous Leukemia or Myelodysplastic syndrome to allow for rapid engraftment with a lower relapse rate therefore improving the therapeutic outcomes
Read the detailed description
Treatment:
The HuM195-Gelonin conjugate has been designed to target leukemia cells and destroy them.
This treatment is divided into 3 parts.
Part I:
MOBILIZATION and STEM CELL COLLECTION:
This is the process that allows for collection of the autologous stem cells (the cells that will be used to do the transplant). All participants will receive the drug idarubicin by vein for 3 days together with cytarabine by vein for 3 days. This will be followed by injections of filgrastim (Neupogen) under the skin twice a day until the white count has recovered and the stem cells are collected. During the process, the number of stem cells in the blood will be measured. When the number of cells reach a certain level, participants will go through a collection procedure known as apheresis.
The apheresis procedure includes collecting blood through a large catheter placed under the collarbone or in the arm with the assistance of a device known as a cell separator. This device separates the stem cells from the rest of the blood and returns the rest of the blood to the participant. The procedure is usually done as an outpatient and takes between 4-5 hours to perform. Most patients collect enough cells for a transplant after 1 or 2 procedures. In this study, a maximum of 5 procedures are allowed.
Participants who are unable to have enough cells collected to take part in the study procedures, will be taken off study and offered alternative standard or investigational therapy. Participants will be able to leave the hospital with physician approval. They will then be monitored on a daily basis until the white blood cell count has recovered (usually 4-5 weeks). The stem cell collection can be done as either an inpatient or outpatient procedure depending on the participant's condition.
Part II:
PURGING PROCEDURE:
The stem cells that are collected through the apheresis procedure are treated in the laboratory with the Hum195/Gelonin conjugate. This procedure is known as purging and it is being studied to learn if the treatment of the stem cells with the HuM195/Gelonin conjugate can eliminate leukemia cells without damaging the normal stem cells. Since the best dose of HuM195/Gelonin conjugate for purging is not known, the cells of the participants in this study will receive 1 of 3 different doses of HuM195/Gelonin. The dose of HuM195/Gelonin that the cells will receive will be decided randomly according to the experience of the participants treated earlier in the study.
The first 3 participants in this study will receive cells that have not been treated with HuM195/Gelonin
After the cells have been treated, they are frozen for future use after the high dose busulfan treatment is given. As a safety measure, all participants will need to have a proportion of untreated stem cells as a back up. These can come from the original stem cell harvest or from a bone marrow harvest.
Part III:
HIGH DOSE FLUDARABINE/BUSULFAN WITH AUTOLOGOUS STEM CELL TRANSPLANT:
All participants who had enough cells treated with HuM195-Gelonin conjugate will then receive busulfan. Busulfan will be given by vein once a day for four days. It will be given together with fludarabine by vein once a day for 4 days. Three days after participants receive the last dose of busulfan, they will receive their previously stored stem cells through a blood transfusion. All participants will receive supportive care. This will include antibiotics, transfusions of blood products, extra nutrients, pain medication, and medications that will quicken the recovery of white blood cells. Participants will be on study for at least 12 months after the stem cell transplant coming for regular check ups.
All participants will have busulfan blood levels checked at specific times before, during and after busulfan infusion. On occasion more blood levels may be drawn. Levels are drawn through a small needle placed in the hands or arms of the patients and removed after the last busulfan blood draw. The busulfan dose administered MAY be modified according to the levels to prevent side effects. Two teaspoons of blood will be drawn for these measurements each time.
Participants will remain in the hospital for about 4-6 weeks and as an outpatient for 1 to 3 months. After participants leave the Medical Center Area, they will be seen in the transplant center every 3 to 6 months for 2 years.
This is an investigational study. The FDA has authorized the use of the HuM195-Gelonin conjugate in research only. Fludarabine has been previously approved for treatment of chronic lymphocytic leukemia by the FDA. The injectable solution of busulfan is a new preparation that has been approved by the FDA for allogeneic transplantation for chronic myelogenous leukemia (CML). The use of these drugs in this study is investigational. Up to 24 patients will be enrolled on this study. All will be enrolled at UTMDACC.
- Being tested
- Gelonin, Busulfan, Fludarabine
- Keywords
- AML, MDS, Gelonin, Purging, Transplant, Peripheral Stem Cell
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GeloninProcedure or surgery
Also called HuM195-Gelonin conjugate
Gelonin-AntiCD33 purging, 3 purging concentrations (fixed dose of 5 x 10^6 CD34+ cells/kg to be infused) with 3 dose levels of 1 nanomolar, 5.0 nanomolar and 10.0 nanomolar.
BusulfanDrug
Also called Busulfex, Myleran
130 mg/m2 in normal saline over three (3) hours IV every twenty-four (24) hours for four (4) consecutive days (days -6 to -3).
FludarabineDrug
Also called Fludara, Fludarabine Phosphate
40 mg/m2 in 100 ml of saline over one (1) hour on each of four (4) consecutive days (days - 6 to -3).
| Study group | Role | What they receive |
|---|---|---|
| Gelonin Purging of ASCT | Experimental | Gelonin Purging of Autologous Stem Cells for Transplantation (ASCT) + Fludara/Busulfan Receives: Procedure: Gelonin; Drug: Busulfan; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal Dose Gelonin
Dose-finding success, defined as patient alive and engrafted at day 28 post transplant, represented as number of patient successes with 3 differing doses (5, 10, or 15 nanomolar (nm) gelonin-antiCD33 purged autologous stem cells after a high dose fludarabine/busulfan conditioning regimen).
Measured: 28 days post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2002 (estimated)
- Study startJul 2002
- Primary completionMar 2005
- Study completionMar 2005
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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sergio A. Giralt, MD, Principal investigator, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00043810
- Sponsor's protocol ID
- ID02-060
- Status last verified
- Oct 2018
- First submitted
- 14 Aug 2002
- Last updated
- 31 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Finding Study of Gelonin Purging of Autologous Stem Cells for Transplantation of Patients With AML/MDS in First or Subsequent Remission
- ClinicalTrials.gov ID
- NCT00043810
- Acronym / sponsor ID
- ID02-060
- Keywords
- AML, MDS, Gelonin, Purging, Transplant, Peripheral Stem Cell
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Jul 2002
- Primary completion
- Mar 2005 (actual)
- Study completion
- Mar 2005 (actual)
- First posted
- 15 Aug 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.
Patients with Acute Myelogenous Leukemia or Myelodysplastic are able to achieve a complete remission but fail to achieve a prolonged disease-free survival. High dose chemotherapy and autologous bone marrow transplantation has been shown to be effective in this group of patients but hematopoietic recovery is slow, and infectious or bleeding complications are common. The delay in hematopoietic recover is accentuated by the use of purging techniques. This is a novel purging approach for autologous stem cell transplantation in patients with Acute Myelogenous Leukemia or Myelodysplastic syndrome to allow for rapid engraftment with a lower relapse rate therefore improving the therapeutic outcomes
Detailed description
Treatment:
The HuM195-Gelonin conjugate has been designed to target leukemia cells and destroy them.
This treatment is divided into 3 parts.
Part I:
MOBILIZATION and STEM CELL COLLECTION:
This is the process that allows for collection of the autologous stem cells (the cells that will be used to do the transplant). All participants will receive the drug idarubicin by vein for 3 days together with cytarabine by vein for 3 days. This will be followed by injections of filgrastim (Neupogen) under the skin twice a day until the white count has recovered and the stem cells are collected. During the process, the number of stem cells in the blood will be measured. When the number of cells reach a certain level, participants will go through a collection procedure known as apheresis.
The apheresis procedure includes collecting blood through a large catheter placed under the collarbone or in the arm with the assistance of a device known as a cell separator. This device separates the stem cells from the rest of the blood and returns the rest of the blood to the participant. The procedure is usually done as an outpatient and takes between 4-5 hours to perform. Most patients collect enough cells for a transplant after 1 or 2 procedures. In this study, a maximum of 5 procedures are allowed.
Participants who are unable to have enough cells collected to take part in the study procedures, will be taken off study and offered alternative standard or investigational therapy. Participants will be able to leave the hospital with physician approval. They will then be monitored on a daily basis until the white blood cell count has recovered (usually 4-5 weeks). The stem cell collection can be done as either an inpatient or outpatient procedure depending on the participant's condition.
Part II:
PURGING PROCEDURE:
The stem cells that are collected through the apheresis procedure are treated in the laboratory with the Hum195/Gelonin conjugate. This procedure is known as purging and it is being studied to learn if the treatment of the stem cells with the HuM195/Gelonin conjugate can eliminate leukemia cells without damaging the normal stem cells. Since the best dose of HuM195/Gelonin conjugate for purging is not known, the cells of the participants in this study will receive 1 of 3 different doses of HuM195/Gelonin. The dose of HuM195/Gelonin that the cells will receive will be decided randomly according to the experience of the participants treated earlier in the study.
The first 3 participants in this study will receive cells that have not been treated with HuM195/Gelonin
After the cells have been treated, they are frozen for future use after the high dose busulfan treatment is given. As a safety measure, all participants will need to have a proportion of untreated stem cells as a back up. These can come from the original stem cell harvest or from a bone marrow harvest.
Part III:
HIGH DOSE FLUDARABINE/BUSULFAN WITH AUTOLOGOUS STEM CELL TRANSPLANT:
All participants who had enough cells treated with HuM195-Gelonin conjugate will then receive busulfan. Busulfan will be given by vein once a day for four days. It will be given together with fludarabine by vein once a day for 4 days. Three days after participants receive the last dose of busulfan, they will receive their previously stored stem cells through a blood transfusion. All participants will receive supportive care. This will include antibiotics, transfusions of blood products, extra nutrients, pain medication, and medications that will quicken the recovery of white blood cells. Participants will be on study for at least 12 months after the stem cell transplant coming for regular check ups.
All participants will have busulfan blood levels checked at specific times before, during and after busulfan infusion. On occasion more blood levels may be drawn. Levels are drawn through a small needle placed in the hands or arms of the patients and removed after the last busulfan blood draw. The busulfan dose administered MAY be modified according to the levels to prevent side effects. Two teaspoons of blood will be drawn for these measurements each time.
Participants will remain in the hospital for about 4-6 weeks and as an outpatient for 1 to 3 months. After participants leave the Medical Center Area, they will be seen in the transplant center every 3 to 6 months for 2 years.
This is an investigational study. The FDA has authorized the use of the HuM195-Gelonin conjugate in research only. Fludarabine has been previously approved for treatment of chronic lymphocytic leukemia by the FDA. The injectable solution of busulfan is a new preparation that has been approved by the FDA for allogeneic transplantation for chronic myelogenous leukemia (CML). The use of these drugs in this study is investigational. Up to 24 patients will be enrolled on this study. All will be enrolled at UTMDACC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gelonin Purging of ASCT | Experimental | Procedure: Gelonin, Drug: Busulfan, Drug: FludarabineGelonin Purging of Autologous Stem Cells for Transplantation (ASCT) + Fludara/Busulfan |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Patients with AML, RAEB-t, RAEB, or CMML who are in first remission and have poor prognosis cytogenetic abnormalities (i.e: deletions of chromosome 5, 7, 20; trisomy 8, t9,22,11q23 abnormalities or complex karyotypes).*
- Patients with AML, RAEB-t, RAEB, or CMML who are in second or subsequent remission.
- Remission is defined as ANC>1.5 x 109/Lt; Platelet count >100 x 109/Lt, and red cell transfusion independence.
- Male or female who have provided written informed consent.
- Tumor cells must be > 80 % CD-33 positive by flow cytometry.
Key exclusion criteria (1 listed)
- Active CNS disease
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 |
|---|---|---|
| GeloninAlso: HuM195-Gelonin conjugateGelonin-AntiCD33 purging, 3 purging concentrations (fixed dose of 5 x 10^6 CD34+ cells/kg to be infused) with 3 dose levels of 1 nanomolar, 5.0 nanomolar and 10.0 nanomolar. | Procedure or surgery | Gelonin Purging of ASCT |
| BusulfanAlso: Busulfex, Myleran130 mg/m2 in normal saline over three (3) hours IV every twenty-four (24) hours for four (4) consecutive days (days -6 to -3). | Drug | Gelonin Purging of ASCT |
| FludarabineAlso: Fludara, Fludarabine Phosphate40 mg/m2 in 100 ml of saline over one (1) hour on each of four (4) consecutive days (days - 6 to -3). | Drug | Gelonin Purging of ASCT |
Primary outcome
Optimal Dose Gelonin
Time frame: 28 days post transplant
Dose-finding success, defined as patient alive and engrafted at day 28 post transplant, represented as number of patient successes with 3 differing doses (5, 10, or 15 nanomolar (nm) gelonin-antiCD33 purged autologous stem cells after a high dose fludarabine/busulfan conditioning regimen).
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2018.
- UT MD Anderson Cancer Center websiteLink 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.
Sergio A. Giralt, MD principal investigator
UT MD 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 Gelonin, Busulfan and Fludarabine 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 18 inclusion and 1 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 31 Oct 2018. 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 was stopped early. 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?
Optimal Dose Gelonin (time frame: 28 days post transplant). 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 31 Oct 2018.