Breast CancerPhase 2NCT00074269
Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Breast Cancer
A Phase 2 study testing anti-thymocyte globulin, filgrastim and graft-versus-tumor induction therapy in people with Breast Cancer, run by University of California, San Diego at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of tumor 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 18 to 60 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- anti-thymocyte globulin, filgrastim and graft-versus-tumor induction therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2003to Mar 2008
- 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 18 to 60 years
- Women only
- No healthy volunteers
- Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the breast
- Metastatic disease
- Meets 1 of the following criteria:
- Chemotherapy-unresponsive disease defined as 1 of the following:
- Less than a partial response to 2 consecutive chemotherapy regimens that included an anthracycline and a taxane in combination or succession
- Progression of disease during or within 3 months of completion of a taxane, anthracycline, or platinol-based regimen
- Histologically confirmed tumor involvement on bone marrow biopsy
- Measurable or evaluable disease* defined as the following:
- Bidimensionally reproducible measurable mass by physical examination, ultrasonography, radiography, CT scan, or MRI
- Evaluable lesions apparent on clinical exam, x-ray, CT scan, or MRI which do not fit the criteria for measurability (e.g., ill-defined post-surgical masses or masses assessable in 1 dimension only)
- Elevation of biological markers (e.g., CA 27.29) is considered evaluable disease NOTE: *Bone lesions or pleural or peritoneal effusion alone are not considered measurable or evaluable disease
- Appropriate candidate for allogeneic stem cell transplantation
- No active CNS metastases
- Available HLA-identical sibling donor
- 6/6 antigen match
- Donor CD34 cells at least 2 times 10^6/kg recipient weight
- Hormone receptor status:
- Estrogen receptor negative or positive
- Estrogen receptor positive tumors must demonstrate progression on at least 1 hormonal manipulation
PATIENT CHARACTERISTICS:
Age
- 18 to 60
Sex
- Female
Menopausal status
- Not specified
Performance status
- Karnofsky 70-100% OR
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- WBC at least 1,500/mm^3
- Platelet count at least 30,000/mm^3
Hepatic
- Bilirubin less than 3 times normal*
- AST and ALT less than 3 times normal* NOTE: *Unless abnormality due to malignancy
Renal
- Creatinine no greater than 1.6 mg/dL
Cardiovascular
- LVEF greater than 40% by echocardiography or MUGA
- No myocardial infarction within the past 6 months
Pulmonary
- DLCO greater than 40% of predicted
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No serious localized or systemic infection
- No hypersensitivity to E. coli-derived products
- No history of non-breast malignant disease within the past 5 years except completely excised nonmelanoma skin cancer or carcinoma in situ of the cervix
- No chronic inflammatory disorder requiring concurrent glucocorticosteroids or other immunosuppressive medication
- No psychological condition or social situation that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- No concurrent glucocorticoids
Radiotherapy
- No prior radiotherapy to an indicator lesion unless the lesion shows evidence of progression after discontinuation of the therapy
Surgery
- Not specified
Other
- No concurrent immunosuppressive medication
Trial locations and contacts
1 site in 1 country.
United States1 site
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, 92093-0658
About this study
Official title: Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer
RATIONALE: Giving chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of tumor 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 tumor cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin, cyclosporine, and methotrexate before or after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well antithymocyte globulin, high-dose melphalan, fludarabine, and allogeneic peripheral stem cell transplant work in treating patients with metastatic adenocarcinoma of the breast.
Read the detailed description
OBJECTIVES:
Primary
- Determine the toxicity and tolerability of allogeneic peripheral blood stem cell transplantation after a nonmyeloablative preparative regimen comprising anti-thymocyte globulin, high-dose melphalan, and fludarabine in women with chemotherapy-refractory or poor-prognosis metastatic adenocarcinoma of the breast.
- Determine the ability of this preparative regimen to facilitate long-term engraftment of allogeneic stem cells and lymphocytes in these patients.
- Determine the response in measurable/evaluable disease and its temporal relationship to the preparative chemotherapy used and to the onset of clinical graft-versus-host disease (GVHD) in patients treated with this regimen.
Secondary
- Determine the progression-free and overall survival of patients treated with this regimen.
- Determine the tumor response and its temporal relationship to administration of high-dose chemotherapy and to the onset of GVHD in patients treated with this regimen.
- Determine the frequency and durability of the induction of full donor chimerism of lymphocytes in patients treated with this regimen.
OUTLINE: This is a nonrandomized, pilot study.
- Nonmyeloablative preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, anti-thymocyte globulin IV over 4 hours on days -7 to -4, and high-dose melphalan IV over 30 minutes on days -3 and -2.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (and then orally when tolerated) every 12 hours beginning on day -4 and tapered after day 42 (if no GVHD occurs) or after day 90 (if grade I acute GVHD occurs). Patients also receive methotrexate IV on days 1, 3, and 6.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0 and continuing until blood counts recover.
- Donor lymphocyte infusion (DLI): Patients who show disease progression or fail to achieve full donor type T-cell chimerism (at least 90% donor derived T-cells) by the 90-day assessment posttransplantation, and have no evidence of active GVHD may receive DLI. Patients who have unresponsive disease with no active GVHD receive subsequent DLIs every 6-8 weeks.
Patients are followed at 1, 3, 6, 12, 18, 24, 30, and 36 months.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
- Conditions
- Breast Cancer
- Being tested
- anti-thymocyte globulin, filgrastim, graft-versus-tumor induction therapy, therapeutic allogeneic lymphocytes, cyclosporine
- Keywords
- recurrent breast cancer, stage IV breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
filgrastimBiological
graft-versus-tumor induction therapyBiological
therapeutic allogeneic lymphocytesBiological
cyclosporineDrug
melphalanDrug
methotrexateDrug
peripheral blood stem cell transplantationProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | Not described Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Biological: graft-versus-tumor induction therapy; Biological: therapeutic allogeneic lymphocytes; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: melphalan; Drug: methotrexate; Procedure: peripheral blood stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Measured: 5 years post transplant
Number of Participants With Long-term Engraftment of Allogeneic Stem Cells and Lymphocytes
Long-term Engraftment of Allogeneic Stem Cells and Lymphocytes based on cell counts of ANC >1000 for 3 consecutive days and platelet count of >50,000
Measured: 30 days post transplant
Number of Participants With Acute and Chronic Graft-versus-host Disease (GVHD)
Measured: 100 days post transplant
Secondary outcomes (4)
Progression-free Survival
Progression assessed by CT scan
Measured: From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Overall Survival
Measured: 1 year from the time of transplant
Response as Measured at 12 Months Post Allografting
response (partial and complete) assessed by CT scan at 12 months post allografting
Measured: From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Frequency of the Induction of Full Donor Chimerism of Lymphocytes as Measured at 1 Month Post Allografting
Measured: 1 month post allografting
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2003 (estimated)
- Study startJul 2003
- Primary completionMar 2008
- Study completionMar 2008
Why it stopped: Terminated early due to poor enrollment
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 Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Edward Ball, University of California, San Diego
- Investigators
- Edward D. Ball, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00074269
- Sponsor's protocol ID
- 020815
- Other IDs
- CDR0000343758
- Status last verified
- May 2023
- First submitted
- 10 Dec 2003
- Last updated
- 5 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00074269
- Acronym / sponsor ID
- 020815
- Conditions
- Breast Cancer
- Keywords
- recurrent breast cancer, stage IV breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated early due to poor enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2003
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 11 Dec 2003 (estimated)
- Results
- Posted 24 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of tumor 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 tumor cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin, cyclosporine, and methotrexate before or after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well antithymocyte globulin, high-dose melphalan, fludarabine, and allogeneic peripheral stem cell transplant work in treating patients with metastatic adenocarcinoma of the breast.
Detailed description
OBJECTIVES:
Primary
- Determine the toxicity and tolerability of allogeneic peripheral blood stem cell transplantation after a nonmyeloablative preparative regimen comprising anti-thymocyte globulin, high-dose melphalan, and fludarabine in women with chemotherapy-refractory or poor-prognosis metastatic adenocarcinoma of the breast.
- Determine the ability of this preparative regimen to facilitate long-term engraftment of allogeneic stem cells and lymphocytes in these patients.
- Determine the response in measurable/evaluable disease and its temporal relationship to the preparative chemotherapy used and to the onset of clinical graft-versus-host disease (GVHD) in patients treated with this regimen.
Secondary
- Determine the progression-free and overall survival of patients treated with this regimen.
- Determine the tumor response and its temporal relationship to administration of high-dose chemotherapy and to the onset of GVHD in patients treated with this regimen.
- Determine the frequency and durability of the induction of full donor chimerism of lymphocytes in patients treated with this regimen.
OUTLINE: This is a nonrandomized, pilot study.
- Nonmyeloablative preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, anti-thymocyte globulin IV over 4 hours on days -7 to -4, and high-dose melphalan IV over 30 minutes on days -3 and -2.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (and then orally when tolerated) every 12 hours beginning on day -4 and tapered after day 42 (if no GVHD occurs) or after day 90 (if grade I acute GVHD occurs). Patients also receive methotrexate IV on days 1, 3, and 6.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0 and continuing until blood counts recover.
- Donor lymphocyte infusion (DLI): Patients who show disease progression or fail to achieve full donor type T-cell chimerism (at least 90% donor derived T-cells) by the 90-day assessment posttransplantation, and have no evidence of active GVHD may receive DLI. Patients who have unresponsive disease with no active GVHD receive subsequent DLIs every 6-8 weeks.
Patients are followed at 1, 3, 6, 12, 18, 24, 30, and 36 months.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Biological: graft-versus-tumor induction therapy, Biological: therapeutic allogeneic lymphocytes, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: melphalan, Drug: methotrexate, Procedure: peripheral blood stem cell transplantation |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- 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 | Biological | treatment |
| filgrastim | Biological | treatment |
| graft-versus-tumor induction therapy | Biological | treatment |
| therapeutic allogeneic lymphocytes | Biological | treatment |
| cyclosporine | Drug | treatment |
| fludarabine phosphate | Drug | treatment |
| melphalan | Drug | treatment |
| methotrexate | Drug | treatment |
| peripheral blood stem cell transplantation | Procedure or surgery | treatment |
Primary outcome
Number of Participants With Adverse Events
Time frame: 5 years post transplant
Number of Participants With Long-term Engraftment of Allogeneic Stem Cells and Lymphocytes
Time frame: 30 days post transplant
Long-term Engraftment of Allogeneic Stem Cells and Lymphocytes based on cell counts of ANC >1000 for 3 consecutive days and platelet count of >50,000
Number of Participants With Acute and Chronic Graft-versus-host Disease (GVHD)
Time frame: 100 days post transplant
4 secondary outcomes
Progression-free Survival
Time frame: From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Overall Survival
Time frame: 1 year from the time of transplant
Response as Measured at 12 Months Post Allografting
Time frame: From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Frequency of the Induction of Full Donor Chimerism of Lymphocytes as Measured at 1 Month Post Allografting
Time frame: 1 month post allografting
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Edward D. Ball, MD principal investigator
University of California, San Diego
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 anti-thymocyte globulin, filgrastim and graft-versus-tumor induction therapy in people with Breast Cancer, run by University of California, San Diego 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: stopped early, as of the sponsor's last update on 5 Jun 2023. 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 24 Nov 2014). 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 With Adverse Events (time frame: 5 years post transplant). The study lists 3 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 5 Jun 2023.