Chronic Myeloproliferative DisordersNCT00290641
Chemotherapy and Total-Body Irradiation Followed by Donor Umbilical Cord Blood Transplant, Cyclosporine, and Mycophenolate Mofetil in Treating Patients With Hematologic Cancer
A study testing filgrastim, graft-versus-tumor induction therapy and cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages Up to 45 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- filgrastim, graft-versus-tumor induction therapy and cyclophosphamide
- Type of treatment
- Surgery or procedure
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2001to Jan 2006
- Phase
- Interventional
- 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 Up to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Diagnosis of a hematologic malignancy of 1 of the following types:
- Acute myeloid leukemia (AML), meeting the following criteria:
- In complete remission (CR) by morphology (< 5% blasts in the bone marrow), as defined by 1 of the following:
- In first CR (CR1) and meets ≥ 1 of the following high-risk criteria:
- High-risk cytogenetics (e.g., those associated with myelodysplastic syndromes [MDS] or complex karotype)
- Preceding MDS
- More than 2 courses of therapy was required to obtain CR
- In second or greater CR
- No morphologic relapse
- Cytogenetic relapse or persistent disease allowed
- Acute lymphocytic leukemia (ALL), meeting the following criteria:
- In CR, as defined by 1 of the following:
- In CR1 and meets ≥ 1 of the following high-risk criteria:
- Unfavorable high-risk cytogenetics [t(9;22), t(1;19), t(4;11) or other MLL rearrangements]
- More than 1 course of therapy was required to obtain CR
- In second or greater CR
- No morphologic relapse or persistent disease
- Chronic myelogenous leukemia (CML), excluding refractory blast crisis
- Advanced myelofibrosis
- Advanced myelodysplasia (blasts < 10% [otherwise need AML induction pre-transplant]), meeting ≥ 1 of the following criteria:
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Refractory anemia with severe pancytopenia
- High-risk cytogenetics
- Non-Hodgkin's lymphoma (NHL), meeting the following criteria:
- One of the following histologic subtypes:
- Mantle cell NHL
- Disease progression after initial therapy (e.g., CHOP)
- Beyond CR1 or beyond first partial remission (PR)
- Intermediate-grade NHL in second or greater CR or PR
- High-grade NHL
- Stage III or IV disease AND received initial therapy
- Stage I or II disease at diagnosis that subsequently progressed after a prior response duration of < 1 year
- No chemotherapy-refractory NHL (i.e., < progressive disease after > 2 salvage regimens)
- Donor available, meeting the following criteria:
- No other existing HLA-identical related donor available
- 4-6/6 HLA-A, -B, and -DRB1, matched unrelated donor by molecular techniques
- A and B to antigen level resolution
- DR to allele resolution
- Umbilical cord blood (UCB) graft may consist of one or two UCB units NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
- Karnofsky score 80-100% (for adults) OR
- Lansky score 50-100% (for children)
- Creatinine ≤ 2.0 mg/dL (for adults) OR creatinine clearance > 40 mL/min (for children)
- Adults with a creatinine > 1.2 mg/dL or a history of renal dysfunction must have a creatinine clearance > 40 mL/min
- Bilirubin ≤ 2 times normal
- AST and ALT ≤ 2 times normal
- Alkaline phosphatase ≤ 2 times normal
- Pulmonary function > 50 % of normal
- LVEF ≥ 45%
- No active infection, including Aspergillus or other mold, within the past 30 days
- No history of HIV infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior myeloablative transplant within the past 6 months if ≤ 18 years old
- No prior myeloablative allotransplant or autologous transplant if > 18 years old
- No prior extensive therapy (e.g., > 12 months of alkylating therapy or > 6 months of alkylating therapy with extensive radiation)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota Cancer Center
Minneapolis, Minnesota, 55455
About this study
Official title: A Cyclophosphamide/Fludarabine/Total Body Irradiation Preparative Regimen for Patients With Hematological Malignancy Receiving Unrelated Donor Umbilical Cord Blood Transplantation
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving chemotherapy together with total-body irradiation followed by donor umbilical cord blood transplant, cyclosporine, and mycophenolate mofetil works in treating patients with hematologic cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the engraftment potential of unrelated allogeneic umbilical cord blood (UCB) using nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with hematologic malignancies.
Secondary
- Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment in patients treated with this regimen.
- Determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients treated with this regimen.
- Determine the incidence of malignant relapse in patients treated with this regimen.
- Determine the 1- and 2-year survival and event-free survival of patients treated with this regimen.
- Determine the phenotype and function of immune cells recovering after UCB transplantation in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: Patients are stratified according to HLA disparity (0-1 vs 2) and number of graft units (1 vs 2).
- Nonmyeloablative conditioning: Patients receive nonmyeloablative conditioning comprising fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation twice daily on days -4 to -1.
- Unrelated allogeneic umbilical cord blood transplantation (UCBT): Patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
- Immunosuppression: Patients receive cyclosporine orally or IV over 2 hours 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper in the absence of graft-vs-host disease (GVHD). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 30, continuing beyond day 30 if no donor engraftment. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
- Being tested
- filgrastim, graft-versus-tumor induction therapy, cyclophosphamide, cyclosporine, fludarabine phosphate
- Keywords
- adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), adult acute myeloid leukemia with t(8;21)(q22;q22), childhood acute myeloid leukemia in remission, secondary acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, refractory anemia with excess blasts, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, noncontiguous stage II adult Burkitt lymphoma, recurrent adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Accelerated Phase, Leukemia, Myeloid, Chronic-Phase, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
graft-versus-tumor induction therapyBiological
cyclophosphamideDrug
cyclosporineDrug
umbilical cord blood transplantationProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment as measured by an absolute neutrophil count of donor origin > 0.5 x 109 /L for 3 days by day 42
Secondary outcomes (2)
Incidence and severity of acute or chronic graft-versus-host-disease, relapse, or mortality at day 100
Survival and event-free survival by Kaplan-Meier estimation at 1 and 2 years after umbilical cord blood (UCB) transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2006 (estimated)
- Study startApr 2001
- Primary completionJan 2006
- Study completionJan 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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 N/A
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Claudio G. Brunstein, MD, PhD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00290641
- Sponsor's protocol ID
- 2000LS068
- Other IDs
- MT2000-25
- Status last verified
- Nov 2017
- First submitted
- 9 Feb 2006
- Last updated
- 29 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS, Verfaillie CM, Wagner JE. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005 Feb 1;105(3):1343-7. doi: 10.1182/blood-2004-07-2717. Epub 2004 Oct 5.
PubMed 15466923
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cyclophosphamide/Fludarabine/Total Body Irradiation Preparative Regimen for Patients With Hematological Malignancy Receiving Unrelated Donor Umbilical Cord Blood Transplantation
- ClinicalTrials.gov ID
- NCT00290641
- Acronym / sponsor ID
- 2000LS068
- Keywords
- adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), adult acute myeloid leukemia with t(8;21)(q22;q22), childhood acute myeloid leukemia in remission, secondary acute myeloid leukemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2001
- Primary completion
- Jan 2006 (actual)
- Study completion
- Jan 2006 (actual)
- First posted
- 13 Feb 2006 (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.
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving chemotherapy together with total-body irradiation followed by donor umbilical cord blood transplant, cyclosporine, and mycophenolate mofetil works in treating patients with hematologic cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the engraftment potential of unrelated allogeneic umbilical cord blood (UCB) using nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with hematologic malignancies.
Secondary
- Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment in patients treated with this regimen.
- Determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients treated with this regimen.
- Determine the incidence of malignant relapse in patients treated with this regimen.
- Determine the 1- and 2-year survival and event-free survival of patients treated with this regimen.
- Determine the phenotype and function of immune cells recovering after UCB transplantation in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: Patients are stratified according to HLA disparity (0-1 vs 2) and number of graft units (1 vs 2).
- Nonmyeloablative conditioning: Patients receive nonmyeloablative conditioning comprising fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation twice daily on days -4 to -1.
- Unrelated allogeneic umbilical cord blood transplantation (UCBT): Patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
- Immunosuppression: Patients receive cyclosporine orally or IV over 2 hours 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper in the absence of graft-vs-host disease (GVHD). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 30, continuing beyond day 30 if no donor engraftment. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| filgrastim | Biological | – |
| graft-versus-tumor induction therapy | Biological | – |
| cyclophosphamide | Drug | – |
| cyclosporine | Drug | – |
| fludarabine phosphate | Drug | – |
| mycophenolate mofetil | Drug | – |
| umbilical cord blood transplantation | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Engraftment as measured by an absolute neutrophil count of donor origin > 0.5 x 109 /L for 3 days by day 42
2 secondary outcomes
Incidence and severity of acute or chronic graft-versus-host-disease, relapse, or mortality at day 100
Survival and event-free survival by Kaplan-Meier estimation at 1 and 2 years after umbilical cord blood (UCB) transplant
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 29 Nov 2017.
- Results publication: PubMed 15466923Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS, Verfaillie CM, Wagner JE. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005 Feb 1;105(3):1343-7. doi: 10.1182/blood-2004-07-2717. Epub 2004 Oct 5.
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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.
Claudio G. Brunstein, MD, PhD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing filgrastim, graft-versus-tumor induction therapy and cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Masonic Cancer Center, University of Minnesota 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?
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 29 Nov 2017. 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.
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 as measured by an absolute neutrophil count of donor origin > 0.5 x 109 /L for 3 days by day 42. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00290641, which also lists 1 linked publication.
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 29 Nov 2017.