Graft FailurePhase 2NCT00472329
Fludarabine and 400 CGY Total Body Irradiation for Recipients of HLA-Matched or Mis-Matched Family or Unrelated Donor Hematopoietic Stem Cell Transplants Who Have Rejected Their First Allogeneic Stem Cell Transplant
A Phase 2 study testing Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors, fludarabine and TBI in people with Graft Failure, run by Colorado Blood Cancer Institute at 1 site in United States.
Trial summary
Major Objectives A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients who have rejected (<5% T Cell Chimerism) a previous allogeneic hematopoietic stem cell graft by using an allogeneic SCT from an HLA-Identical or non-identical family donor or unrelated donors… Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Graft Failure
- What is being tested?
- Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors, fludarabine and TBI
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Dec 2020
- Phase
- Phase 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 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any patient who has rejected a previous allogeneic transplant (related or unrelated) rejection based on chimerism data from peripheral blood specimens showing loss of donor T Cells.
- Available HLA-identical, a one-antigen mis-matched sibling donor, a phenotypically HLA-matched family member, a phenotypically matched unrelated donor, or a 9/10 matched unrelated donor with a negative cross-match.
- Age ≤ 75 years.
- Patients who fail to engraft or have signs of early relapse after an autologous transplant may be considered for this protocol as salvage treatment if they are presented to the RMBMTP Clinical Care meeting and the majority of the group agrees that this a reasonable treatment option.
Who cannot join
- Patients whose low donor chimerism is felt to be due to rapidly progressive hematological malignancies, unless they can be treated into a minimal disease state with additional treatment.
- Patients with active uncontrolled CNS involvement with malignancy.
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
- Females who are pregnant.
- Patients who are HIV positive
- Organ dysfunction felt to be due to the conditioning for the first transplant including the following:
Show all 12Show fewer
- Left ventricle ejection fraction < 35%.
- DLCO <35% of predicted, or receiving continuous supplementary oxygen.
- Karnofsky score <50 for patients < 60 years, or <70 for patients aged 60 - 69 years (see appendix B).
- Creatinine clearance < 40 ml/min.
- Patients with these end-organ toxicities may be presented to the RMBMTP Patient Care Conference. If the majority opinion is that this treatment is the safest option for a patient who has rejected their first transplant, they will be allowed to undergo the treatment, after informed consent has been signed.
- Patients with a positive PRA or anti-donor T or B cell (+) will be considered for this treatment protocol only if no other option is available. They should not be eligible for another research study. The transplantation group must have a majority opinion that this is the best available option for the patient in question. In patients with either condition, the only acceptable stem cell source will be peripheral blood.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Rocky Mountain Blood and Marrow Transplant Program
Denver, Colorado, 80218
Juli Murphy, 303-285-5087, Juli.Murphy@usoncology.com
Nicole Stephens, 303-336-2183, Nicole.Stephens@usoncology.com
About this study
Major Objectives A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients who have rejected (<5% T Cell Chimerism) a previous allogeneic hematopoietic stem cell graft by using an allogeneic SCT from an HLA-Identical or non-identical family donor or unrelated donors, with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF.
- To evaluate the incidence of transplant related mortality.
Read more
Minor Objectives A. To evaluate the incidence of acute and chronic GVHD after second allogeneic HCT utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors.
- To evaluate disease responses and survival after second allogeneic SCT. C. To evaluate the need for DLI after second transplant for either disease control or persistent mixed chimerism.
Read the detailed description
This protocol will evaluate the use of Fludarabine (150mg/m2) with TBI (400cGy) as pre-transplant conditioning for a second allogeneic stem cell transplant after initial graft rejection. Preliminary data suggest that the combination of Flu/TBI at the proposed doses is safer and more effective than prior second transplantation regimens published to date. As we perform more non-myeloablative transplantations we expect that this issue to arise more frequently. The preliminary data available indicate that the proposed regimen is the safest and most effective to instill donor hematopoiesis after the initial graft has been rejected.
We also wish to evaluate the safety and effectiveness of Tacrolimus and MMF as GVHD prophylaxis in patients receiving a second transplant. Tac/MMF is our current GVHD prophylaxis regimen. It has proven to be well tolerated and provide good protection against GVHD, even in heavily pretreated patients. We propose to use this standard first transplant GVHD prophylaxis to prevent GVHD after second transplantation. DLI may be given in the presence of disease progression or for mixed chimerism as clinically indicated.
- Conditions
- Graft Failure
- Being tested
- Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors, fludarabine, TBI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donorsProcedure or surgery
fludarabineDrug
TBIProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine and 400cGY TBI | No intervention | Not described Receives: Procedure: Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors; Drug: fludarabine; Procedure: TBI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stable allogeneic hematopoietic engraftment with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF.
Measured: Overall disease free survival
Secondary outcomes (1)
Incidence of acute and chronic GVHD after second allogeneic HCT utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors, disease responses and survival after second allogeneic SCT.
Measured: Overall management of acute and chronic GVHD
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2007 (estimated)
- Study startMar 2007
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft FailureStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Colorado Blood Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter McSweeney, M.D., Colorado Blood Cancer Institute
- Investigators
- Mark W Brunvand, MD, Principal investigator, Colorado Blood Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00472329
- Sponsor's protocol ID
- RMBMT-166-A
- Other IDs
- CBCI-166
- Status last verified
- Jun 2014
- First submitted
- 10 May 2007
- Last updated
- 30 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fludarabine and 400 CGY Total Body Irradiation for Recipients of HLA-Matched or Mis-Matched Family or Unrelated Donor Hematopoietic Stem Cell Transplants Who Have Rejected Their First Allogeneic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT00472329
- Acronym / sponsor ID
- RMBMT-166-A
- Conditions
- Graft Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Colorado Blood Cancer InstituteUniversity, hospital or other
- Study start
- Mar 2007
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 11 May 2007 (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.
Major Objectives A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients who have rejected (<5% T Cell Chimerism) a previous allogeneic hematopoietic stem cell graft by using an allogeneic SCT from an HLA-Identical or non-identical family donor or unrelated donors, with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF.
- To evaluate the incidence of transplant related mortality.
Minor Objectives A. To evaluate the incidence of acute and chronic GVHD after second allogeneic HCT utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors.
- To evaluate disease responses and survival after second allogeneic SCT. C. To evaluate the need for DLI after second transplant for either disease control or persistent mixed chimerism.
Detailed description
This protocol will evaluate the use of Fludarabine (150mg/m2) with TBI (400cGy) as pre-transplant conditioning for a second allogeneic stem cell transplant after initial graft rejection. Preliminary data suggest that the combination of Flu/TBI at the proposed doses is safer and more effective than prior second transplantation regimens published to date. As we perform more non-myeloablative transplantations we expect that this issue to arise more frequently. The preliminary data available indicate that the proposed regimen is the safest and most effective to instill donor hematopoiesis after the initial graft has been rejected.
We also wish to evaluate the safety and effectiveness of Tacrolimus and MMF as GVHD prophylaxis in patients receiving a second transplant. Tac/MMF is our current GVHD prophylaxis regimen. It has proven to be well tolerated and provide good protection against GVHD, even in heavily pretreated patients. We propose to use this standard first transplant GVHD prophylaxis to prevent GVHD after second transplantation. DLI may be given in the presence of disease progression or for mixed chimerism as clinically indicated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine and 400cGY TBI | No intervention | Procedure: Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors, Drug: fludarabine, Procedure: TBI |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Any patient who has rejected a previous allogeneic transplant (related or unrelated) rejection based on chimerism data from peripheral blood specimens showing loss of donor T Cells.
- Available HLA-identical, a one-antigen mis-matched sibling donor, a phenotypically HLA-matched family member, a phenotypically matched unrelated donor, or a 9/10 matched unrelated donor with a negative cross-match.
- Age ≤ 75 years.
- Patients who fail to engraft or have signs of early relapse after an autologous transplant may be considered for this protocol as salvage treatment if they are presented to the RMBMTP Clinical Care meeting and the majority of the group agrees that this a reasonable treatment option.
Key exclusion criteria (12 listed)
- Patients whose low donor chimerism is felt to be due to rapidly progressive hematological malignancies, unless they can be treated into a minimal disease state with additional treatment.
- Patients with active uncontrolled CNS involvement with malignancy.
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
- Females who are pregnant.
- Patients who are HIV positive
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 |
|---|---|---|
| Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors | Procedure or surgery | Fludarabine and 400cGY TBI |
| fludarabine | Drug | Fludarabine and 400cGY TBI |
| TBI | Procedure or surgery | Fludarabine and 400cGY TBI |
Primary outcome
Stable allogeneic hematopoietic engraftment with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF.
Time frame: Overall disease free survival
1 secondary outcome
Incidence of acute and chronic GVHD after second allogeneic HCT utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors, disease responses and survival after second allogeneic SCT.
Time frame: Overall management of acute and chronic GVHD
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2014.
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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.
Mark W Brunvand, MD principal investigator
Colorado Blood Cancer Institute
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 Allogeneic hematopoietic stem cell graft using an allogeneic SCT HLA-Identical or non-identical family donor or unrelated donors, fludarabine and TBI in people with Graft Failure, run by Colorado Blood Cancer Institute 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 4 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 30 Jun 2014. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juli Murphy (303-285-5087, Juli.Murphy@usoncology.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stable allogeneic hematopoietic engraftment with fludarabine (150mg/m2) and TBI (400cGy), with post-transplantation immunosuppression utilizing tacrolimus and MMF. (time frame: Overall disease free survival). 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 30 Jun 2014.