Breast CancerPhase 1/2NCT00365287
Combination Chemotherapy and Total-Body Irradiation Before Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer, Metastatic Breast Cancer, or Kidney Cancer
A Phase 1/2 study testing anti-thymocyte globulin, cyclophosphamide and cyclosporine in people with Breast Cancer and Kidney Cancer, run by Masonic Cancer Center, University of Minnesota.
Trial summary
RATIONALE: Giving low doses of chemotherapy 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 when they do not exactly match the patient's blood. Read more about this study
- Who is it for?
- Ages Up to 69 years
- Conditions the study is for
- Breast Cancer, Kidney Cancer, Leukemia
- What is being tested?
- anti-thymocyte globulin, cyclophosphamide and cyclosporine
- Type of treatment
- Surgery or procedure
- How many people
- 148 participants
- Where
- No sites listed yet
- Study dates
- Jun 2000to Dec 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 Up to 69 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following:
- Acute myeloid leukemia (AML), meeting 1 of the following criteria:
- In first complete remission (CR1) by morphology AND at high risk, as evidenced by 1 of the following:
- AML secondary to myelodysplastic syndromes (MDS)
- High-risk cytogenetics, such as those associated with MDS or complex karyotype
- More than 2 courses of therap were required to obtain a CR
- In second or greater CR by morphology
- In morphologic relapse or persistent disease, defined as > 5% blasts in normocellular bone marrow OR any percentage of blasts if blasts have unique morphologic markers (e.g., auer rods)
- In cytogenetic relapse (without morphologic relapse)
- Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:
- In CR1 by morphology AND at high risk, as evidenced by 1 of the following:
- High-risk cytogenetics, such as t(9;22), t(1;19), t(4;11), or other MLL rearrangements
- More than 1 course of therapy was required to obtain a CR
- In second or greater CR by morphology
- In morphologic relapse or persistent disease as defined for AML
- In cytogenetic relapse (without morphologic relapse)
- Chronic myelogenous leukemia
- All types allowed except refractory blast crisis
- Non-Hodgkin's lymphoma (NHL)
- No intermediate- or high-grade NHL or mantle cell NHL that is progressive on salvage therapy
- Stable disease allowed provided it is non-bulky
- Hodgkin's lymphoma
- No progressive disease on salvage therapy
- Stable disease allowed provided it is non-bulky
- Chronic lymphocytic leukemia
- Multiple myeloma
- MDS
- Any subtype allowed, including refractory anemia if there is severe pancytopenia or complex cytogenetics
- Less than 5% blasts
- If patient has blasts ≥ 5% then they must undergo induction therapy before transplantation
- Metastatic breast cancer
- Disease must have responded to recent chemotherapy OR in plateau after response to chemotherapy
- Renal cell cancer
- Acquired bone marrow failure syndromes
- Small percentage of blasts that is equivocal between marrow regeneration vs early relapse allowed provided there are no associated cytogenetic markers consistent with relapse (for patients with AML or ALL)
- Must have a 4/6 HLA-A, -B, and -DRB1 matched unrelated umbilical cord blood donor available
- No 5/6 or 6/6 HLA-A , -B, and -DRB1 matched sibling donor available
- No more than 2 antigen mismatches at the HLA-A, -B, or -DRB1 loci 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 performance status 60-100% OR Lansky performance status 50-100% (pediatric patients)
- Albumin > 2.5 g/dL
- Creatinine ≤ 2.0 mg/dL (adults) OR creatinine clearance > 40 mL/min (pediatric patients)
- Adults with creatinine > 1.2 mg/dL or a history of renal dysfunction must have a creatinine clearance > 40 mL/min
- Transaminases < 5 times upper limit of normal (ULN)
- Bilirubin < 3 times ULN
- LVEF ≥ 35%
- DLCO > 30% of predicted
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of HIV infection or known HIV-positivity
- No decompensated congestive heart failure
- No uncontrolled cardiac arrhythmia
- No requirement for supplemental oxygen
- No active, serious infection
- Recent mold infection (e.g., Aspergillus) allowed provided patient has received ≥ 30 days of appropriate treatment AND infection is controlled and cleared by an infectious disease specialist
PRIOR CONCURRENT THERAPY:
- No prior irradiation that precludes the safe administration of 1 additional dose of 200 cGy of total-body irradiation
- At least 3 months since prior myeloablative bone marrow transplantation
About this study
Official title: Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen
RATIONALE: Giving low doses of chemotherapy 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 when they do not exactly match the patient's blood. 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 antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving combination chemotherapy together with total-body irradiation before donor umbilical cord blood transplant and to see how well they work in treating patients with advanced hematologic cancer, metastatic breast cancer, or kidney cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the safety of nonmyeloablative preparative regimen comprising cyclophosphamide, fludarabine, and total-body irradiation with or without anti-thymocyte globulin, in terms of non-relapse mortality at day 100 post-transplantation, in patients with advanced hematologic malignancies, metastatic breast cancer, or renal cell cancer who are undergoing umbilical cord blood transplantation from an unrelated donor.
Secondary
- Determine the hematopoietic recovery and degree of chimerism on days 21, 60, 100, 180, and 360 post-transplantation.
- Determine the incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) by day 100 post-transplantation and chronic GVHD at 1 year post-transplantation.
- Evaluate the risk of relapse at 1 year post-transplantation.
- Determine overall survival at 1 year post-transplantation.
OUTLINE:
- Nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients also undergo total-body irradiation on day -1. Some patients* may also receive anti-thymocyte globulin (ATG) IV twice daily on days -6 to -4.
NOTE: *Patients who have not had prior combination chemotherapy within the past 3 months OR who only received 1 prior induction course for the treatment of acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndromes, or chronic myelogenous leukemia in blast crisis receive ATG during the preparative regimen.
- Umbilical cord blood transplantation (UCBT): Patients undergo UCBT from an unrelated donor on day 0.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day -3 and continuing until day 30 or until 7 days after engraftment.
After transplantation, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
- Conditions
- Breast Cancer, Kidney Cancer, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Being tested
- anti-thymocyte globulin, cyclophosphamide, cyclosporine, fludarabine phosphate, mycophenolate mofetil
- Keywords
- stage IV breast cancer, recurrent renal cell cancer, stage III renal cell cancer, stage IV renal cell cancer, 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), recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, stage III chronic lymphocytic leukemia
- Medical subject headings
- Breast Neoplasms, Kidney Neoplasms, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinDrug
cyclophosphamideDrug
cyclosporineDrug
radiation therapyProcedure or surgery
umbilical cord blood transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as assessed by a non-relapse mortality < 30% within day 100
Secondary outcomes (1)
Hematopoietic recovery and the degree of chimerism at days 21, 60, 100, 180, and 360 after study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2006 (estimated)
- Study startJun 2000
- Primary completionDec 2005
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies 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 1/2
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 148 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, Study chair, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00365287
- Sponsor's protocol ID
- 2000LS039
- Other IDs
- MT2000-15
- Status last verified
- Nov 2017
- First submitted
- 16 Aug 2006
- Last updated
- 29 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bachanova V, Burke MJ, Yohe S, Cao Q, Sandhu K, Singleton TP, Brunstein CG, Wagner JE, Verneris MR, Weisdorf DJ. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012 Jun;18(6):963-8. doi: 10.1016/j.bbmt.2012.02.012. Epub 2012 Mar 16.
PubMed 22430088Bachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.
PubMed 21403127Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.
PubMed 19179301
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
- Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen
- ClinicalTrials.gov ID
- NCT00365287
- Acronym / sponsor ID
- 2000LS039
- Conditions
- Breast Cancer, Kidney Cancer, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Keywords
- stage IV breast cancer, recurrent renal cell cancer, stage III renal cell cancer, stage IV renal cell cancer, 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)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2000
- Primary completion
- Dec 2005 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 17 Aug 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 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 when they do not exactly match the patient's blood. 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 antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving combination chemotherapy together with total-body irradiation before donor umbilical cord blood transplant and to see how well they work in treating patients with advanced hematologic cancer, metastatic breast cancer, or kidney cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the safety of nonmyeloablative preparative regimen comprising cyclophosphamide, fludarabine, and total-body irradiation with or without anti-thymocyte globulin, in terms of non-relapse mortality at day 100 post-transplantation, in patients with advanced hematologic malignancies, metastatic breast cancer, or renal cell cancer who are undergoing umbilical cord blood transplantation from an unrelated donor.
Secondary
- Determine the hematopoietic recovery and degree of chimerism on days 21, 60, 100, 180, and 360 post-transplantation.
- Determine the incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) by day 100 post-transplantation and chronic GVHD at 1 year post-transplantation.
- Evaluate the risk of relapse at 1 year post-transplantation.
- Determine overall survival at 1 year post-transplantation.
OUTLINE:
- Nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients also undergo total-body irradiation on day -1. Some patients* may also receive anti-thymocyte globulin (ATG) IV twice daily on days -6 to -4.
NOTE: *Patients who have not had prior combination chemotherapy within the past 3 months OR who only received 1 prior induction course for the treatment of acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndromes, or chronic myelogenous leukemia in blast crisis receive ATG during the preparative regimen.
- Umbilical cord blood transplantation (UCBT): Patients undergo UCBT from an unrelated donor on day 0.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day -3 and continuing until day 30 or until 7 days after engraftment.
After transplantation, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older 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 |
|---|---|---|
| anti-thymocyte globulin | Drug | – |
| cyclophosphamide | Drug | – |
| cyclosporine | Drug | – |
| fludarabine phosphate | Drug | – |
| mycophenolate mofetil | Drug | – |
| radiation therapy | Procedure or surgery | – |
| umbilical cord blood transplantation | Procedure or surgery | – |
Primary outcome
Safety as assessed by a non-relapse mortality < 30% within day 100
1 secondary outcome
Hematopoietic recovery and the degree of chimerism at days 21, 60, 100, 180, and 360 after study completion
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.
- Derived from this study: PubMed 22430088Bachanova V, Burke MJ, Yohe S, Cao Q, Sandhu K, Singleton TP, Brunstein CG, Wagner JE, Verneris MR, Weisdorf DJ. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012 Jun;18(6):963-8. doi: 10.1016/j.bbmt.2012.02.012. Epub 2012 Mar 16.
- Derived from this study: PubMed 21403127Bachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.
- Derived from this study: PubMed 19179301Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.
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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 study chair
Masonic Cancer Center, University of Minnesota
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing anti-thymocyte globulin, cyclophosphamide and cyclosporine in people with Breast Cancer and Kidney Cancer, run by Masonic Cancer Center, University of Minnesota.
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.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as assessed by a non-relapse mortality < 30% within day 100. 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 NCT00365287, which also lists 3 linked publications.
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.