Adult Acute Myeloid Leukemia in RemissionPhase 1NCT00093743
Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
A Phase 1 study testing fludarabine phosphate, cyclosporine and total-body irradiation in people with Adult Acute Myeloid Leukemia in Remission and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by Fred Hutchinson Cancer Center at 5 sites in United States.
Trial summary
Based on success in other diseases, the Fred Hutchinson Cancer Research Center (FHCRC) has developed a transplant procedure for Fanconi anemia (FA), which does not completely destroy the patient's remaining bone marrow. It should also be less harmful (toxic). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)
- What is being tested?
- fludarabine phosphate, cyclosporine and total-body irradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 5 sitesUnited States
- Study dates
- Jan 2000to Sep 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Any patient with marrow failure and increased chromosome fragility as determined in the diepoxybutane (DEB) or mitomycin C test
- Any patient with Fanconi anemia (FA) with marrow failure meeting the following criteria:
- Granulocyte count < 0.2 x 10^9/L
- Platelet count < 20 x 10^9/L
- Hemoglobin < 8 g/dl
- Corrected reticulocyte count <1%
Show all 10Show fewer
- Any patient with FA as determined by DEB fragility, who has life-threatening marrow failure involving a single hematopoietic lineage
- Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (myelodysplastic syndromes [MDS] or acute myeloid leukemia [AML]) in remission
- DONOR: Unrelated Donors who are prospectively: Matched for human lymphocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined by high resolution typing); only a single allele disparity will be allowed for HLA -A, B, or C as defined by high resolution typing
- DONOR: HLA typing will be performed at the highest level of resolution available at the time of transplant
Who cannot join
- Evidence for hematopoietic malignancy in relapse
- Heart or lung disease that would prevent compliance with conditioning and GvHD regimen or would severely limit the probability of survival
- Human immunodeficiency virus (HIV) seropositive patients
- Females who are pregnant or breastfeeding, or unwilling to use contraceptive techniques during and for the 12 months following treatment
- DONOR: Donors who by DEB testing are found to have FA
- DONOR: Donors who test positive in the lymphocytotoxic crossmatch assay
- DONOR: Donors who are HIV positive
- DONOR: Donors who for other medical or psychological reasons are not suitable as donors
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, 60611
Riley Hospital for Children
Indianapolis, Indiana, 46202
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Low-Dose Total Body Irradiation and Fludarabine Followed By Unrelated Donor Stem Cell Transplantation for Patients With Fanconi Anemia - A Multicenter Trial
Based on success in other diseases, the Fred Hutchinson Cancer Research Center (FHCRC) has developed a transplant procedure for Fanconi anemia (FA), which does not completely destroy the patient's remaining bone marrow. It should also be less harmful (toxic). Researchers wish to test whether this approach can overcome the graft failure often seen when bone marrow or peripheral blood stem cells from an unrelated donor are used. Researchers also will look at whether the procedure is less toxic than a conventional bone marrow transplant (BMT).
Read the detailed description
PRIMARY OBJECTIVES:
- To determine whether donor chimerism can be achieved in patients with Fanconi anemia receiving marrow or peripheral blood stem cell (PBSC) grafts from unrelated donors following low dose total body irradiation (TBI), fludarabine (fludarabine phosphate), mycophenolate mofetil, and cyclosporine.
II. To determine the lowest dose of TBI necessary to achieve donor chimerism in at least 80% of patients.
III. To determine the incidence of severe regimen-related toxicity.
SECONDARY OBJECTIVES:
- To determine the survival of Fanconi anemia patients transplanted with unrelated donor marrow or PBSC grafts after conditioning with a non-myeloablative regimen.
II. To determine the incidence and severity of graft-vs-host disease (GVHD) incurred with unrelated bone marrow or PBSC grafts transplant patients with Fanconi anemia.
III. To determine if mixed chimerism results in amelioration of symptoms associated with bone marrow failure in patients with Fanconi anemia.
OUTLINE:
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
After completion of study treatment, patients are followed up at 6 months and annually thereafter.
- Conditions
- Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
- Being tested
- fludarabine phosphate, cyclosporine, total-body irradiation, allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation
- Medical subject headings
- Congenital Abnormalities, Fanconi Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called 2-F-ara-AMP, Beneflur, Fludara
Given IV
cyclosporineDrug
Also called ciclosporin, cyclosporin, cyclosporin A, CYSP
Given IV or PO
total-body irradiationRadiation
Also called TBI
Undergo TBI
allogeneic bone marrow transplantationProcedure or surgery
Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Undergo allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Undergo allogeneic PBSC transplantation
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo allogeneic PBSC transplantation
Also called Cellcept, MMF
Given PO or IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (allogeneic bone marrow or PBSC transplantation) | Experimental | NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96. Receives: Drug: fludarabine phosphate; Drug: cyclosporine; Radiation: total-body irradiation; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Drug: mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment, defined as donor chimerism (mixed or complete)
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Measured: Day 28
Engraftment, defined as donor chimerism (mixed or complete)
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Measured: Day 56
Engraftment, defined as donor chimerism (mixed or complete)
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Measured: Day 84
Engraftment, defined as donor chimerism (mixed or complete)
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Measured: Day 180
Regimen toxicity assessed using the Bearman scale
Patient data will be summarized using standard statistical methods.
Measured: Up to day 100
Acute GvHD defined using the Seattle criteria
For the evaluation of GvHD, time of onset, severity, and treatment will be recorded. Patient data will be summarized using standard statistical methods.
Measured: Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2004 (estimated)
- Study startJan 2000
- Primary completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Acute Myeloid Leukemia in RemissionStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hans-Peter Kiem, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00093743
- Sponsor's protocol ID
- 1444.00
- Other IDs
- NCI-2012-00593, 1444.00, P30CA015704
- Status last verified
- Feb 2017
- First submitted
- 6 Oct 2004
- Last updated
- 20 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-Dose Total Body Irradiation and Fludarabine Followed By Unrelated Donor Stem Cell Transplantation for Patients With Fanconi Anemia - A Multicenter Trial
- ClinicalTrials.gov ID
- NCT00093743
- Acronym / sponsor ID
- 1444.00
- Conditions
- Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
- Study start
- Jan 2000
- Primary completion
- Sep 2007 (actual)
- First posted
- 8 Oct 2004 (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.
Based on success in other diseases, the Fred Hutchinson Cancer Research Center (FHCRC) has developed a transplant procedure for Fanconi anemia (FA), which does not completely destroy the patient's remaining bone marrow. It should also be less harmful (toxic). Researchers wish to test whether this approach can overcome the graft failure often seen when bone marrow or peripheral blood stem cells from an unrelated donor are used. Researchers also will look at whether the procedure is less toxic than a conventional bone marrow transplant (BMT).
Detailed description
PRIMARY OBJECTIVES:
- To determine whether donor chimerism can be achieved in patients with Fanconi anemia receiving marrow or peripheral blood stem cell (PBSC) grafts from unrelated donors following low dose total body irradiation (TBI), fludarabine (fludarabine phosphate), mycophenolate mofetil, and cyclosporine.
II. To determine the lowest dose of TBI necessary to achieve donor chimerism in at least 80% of patients.
III. To determine the incidence of severe regimen-related toxicity.
SECONDARY OBJECTIVES:
- To determine the survival of Fanconi anemia patients transplanted with unrelated donor marrow or PBSC grafts after conditioning with a non-myeloablative regimen.
II. To determine the incidence and severity of graft-vs-host disease (GVHD) incurred with unrelated bone marrow or PBSC grafts transplant patients with Fanconi anemia.
III. To determine if mixed chimerism results in amelioration of symptoms associated with bone marrow failure in patients with Fanconi anemia.
OUTLINE:
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.
After completion of study treatment, patients are followed up at 6 months and annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (allogeneic bone marrow or PBSC transplantation) | Experimental | Drug: fludarabine phosphate, Drug: cyclosporine, Radiation: total-body irradiation, Procedure: allogeneic bone marrow transplantation, Procedure: allogeneic hematopoietic stem cell transplantation, Procedure: peripheral blood stem cell transplantation, Drug: mycophenolate mofetilNON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Any patient with marrow failure and increased chromosome fragility as determined in the diepoxybutane (DEB) or mitomycin C test
- Any patient with Fanconi anemia (FA) with marrow failure meeting the following criteria:
- Granulocyte count < 0.2 x 10^9/L
- Platelet count < 20 x 10^9/L
- Hemoglobin < 8 g/dl
Key exclusion criteria (8 listed)
- Evidence for hematopoietic malignancy in relapse
- Heart or lung disease that would prevent compliance with conditioning and GvHD regimen or would severely limit the probability of survival
- Human immunodeficiency virus (HIV) seropositive patients
- Females who are pregnant or breastfeeding, or unwilling to use contraceptive techniques during and for the 12 months following treatment
- DONOR: Donors who by DEB testing are found to have FA
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 |
|---|---|---|
| fludarabine phosphateAlso: 2-F-ara-AMP, Beneflur, FludaraGiven IV | Drug | Treatment (allogeneic bone marrow or PBSC transplantation) |
| cyclosporineAlso: ciclosporin, cyclosporin, cyclosporin A, CYSPGiven IV or PO | Drug | Treatment (allogeneic bone marrow or PBSC transplantation) |
| total-body irradiationAlso: TBIUndergo TBI | Radiation | Treatment (allogeneic bone marrow or PBSC transplantation) |
| allogeneic bone marrow transplantationAlso: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrowUndergo allogeneic bone marrow transplantation | Procedure or surgery | Treatment (allogeneic bone marrow or PBSC transplantation) |
| allogeneic hematopoietic stem cell transplantationUndergo allogeneic PBSC transplantation | Procedure or surgery | Treatment (allogeneic bone marrow or PBSC transplantation) |
| peripheral blood stem cell transplantationAlso: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cellUndergo allogeneic PBSC transplantation | Procedure or surgery | Treatment (allogeneic bone marrow or PBSC transplantation) |
| mycophenolate mofetilAlso: Cellcept, MMFGiven PO or IV | Drug | Treatment (allogeneic bone marrow or PBSC transplantation) |
Primary outcome
Engraftment, defined as donor chimerism (mixed or complete)
Time frame: Day 28
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Engraftment, defined as donor chimerism (mixed or complete)
Time frame: Day 56
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Engraftment, defined as donor chimerism (mixed or complete)
Time frame: Day 84
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Engraftment, defined as donor chimerism (mixed or complete)
Time frame: Day 180
Mixed chimerism is defined as presence of 5-95%, complete chimerism as > 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.
Regimen toxicity assessed using the Bearman scale
Time frame: Up to day 100
Patient data will be summarized using standard statistical methods.
Acute GvHD defined using the Seattle criteria
Time frame: Day 84
For the evaluation of GvHD, time of onset, severity, and treatment will be recorded. Patient data will be summarized using standard statistical methods.
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 20 Feb 2017.
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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.
Hans-Peter Kiem principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing fludarabine phosphate, cyclosporine and total-body irradiation in people with Adult Acute Myeloid Leukemia in Remission and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by Fred Hutchinson Cancer Center 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 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Engraftment, defined as donor chimerism (mixed or complete) (time frame: Day 28). The study lists 6 primary outcomes in all. 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 20 Feb 2017.