Leukemia, Myeloid, ChronicPhase 2NCT00167180
Post Transplant Donor Lymphocyte Infusion
A Phase 2 study testing Donor Lymphocyte Infusion and Induction Chemotherapy in people with Leukemia, Myeloid, Chronic and Lymphomas, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
The purpose of this study is to test the hypothesis that a pre-infusion preparative regimen of cyclophosphamide and fludarabine will improve the effectiveness of DLI in patients with blood cancers. Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Leukemia, Myeloid, Chronic, Lymphomas, Multiple Myeloma
- What is being tested?
- Donor Lymphocyte Infusion and Induction Chemotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to 24 Dec 2018
- 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 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients (age > or = 1 years) with a diagnosis of relapse after related or unrelated allogeneic stem cell transplantation for a hematological malignancy.
- For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least two measurements over a 6 month interval. If cytogenetics are normal and there is PCR evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of a quantitative increase in CML measured either by quantitative PCR or by fluorescent in situ hybridization (FISH).
- For non-CML, relapse will be defined based on disease specific morphologic criteria from a bone marrow biopsy and aspirate or recurrence of disease specific cytogenetics. For disease specific definition of relapse, see appendix 3. Relapse can be determined morphologically with less than 5 percent blasts if definitive relapse can be determined. Equivocal results for relapse should result in a repeated test after an appropriate time interval (suggested 1 month) to determine eligibility.
- Post-transplant lymphoproliferative diseases (often referred to as EBV-associated lymphomas) are NOT eligible for this protocol.
- For Chronic Phase CML patients only
- - must have failed (no response in 3 months or incomplete response at 6 months) or refused treatment with Gleevec
Show all 20Show fewer
- - if no prior DLI, CML patients will first have DLI- if relapse occurs after DLI, DLI with chemotherapy per this protocol will be offered
- Patients must be within one year of identification of relapse or if beyond that time period, must have at least 10% donor DNA by RFLP or cytogenetics.
- Same allogeneic donor (sibling or URD) used for transplantation is available for lymphocyte donation.
- No severe organ damage (by laboratory or clinical assessment) as measured by:
- - blood creatinine ≤ 2.0 mg/dL
- - liver function tests < 5 x normal
- - left ventricular ejection fraction > 40% (testing required only if symptomatic or prior known impairment).
- - pulmonary functions > 50% (testing required only if symptomatic or prior known impairment). Oxygen saturation (>92%) can be used in child where PFT's cannot be obtained.
- - chest x-ray without evidence of active infection
- Off prednisone and other immunosuppressive agents (given for any reason) for at least 3 days prior to DLI infusions.
- Performance status ≥ 60%
- Women must not be pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
- Patient must given written informed consent indicating understanding of the nature of the treatment and its potential risks
Who cannot join
- Concurrent signs of acute or chronic graft-versus-host disease requiring ongoing treatment at the time of relapse will be ineligible.
- Patients being treated for GVHD with prednisone, cyclosporine, Imuran or other immunosuppressive medications are not eligible until these medications are discontinued for at least 2 weeks without a flare of GVHD.
- Active CNS leukemia
- Active fungal infection or pulmonary infiltrates (stable prior treated disease is allowable)
- HIV positive
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant
The purpose of this study is to test the hypothesis that a pre-infusion preparative regimen of cyclophosphamide and fludarabine will improve the effectiveness of DLI in patients with blood cancers.
Read the detailed description
When cancer relapses after donor bone marrow transplantation, regular dose chemotherapy offers little hope of prolonged survival. However, there is evidence that lymphocytes can attack cancer cells. There is considerable evidence that this immune attack on cancer cells is associated with graft-versus-host disease. Although graft-versus-host disease can cause problems, this immune reaction may, in part, be the way that bone marrow transplantation cures cancer. In this study we hope that infusion of immune cells from the subject's bone marrow donor plus a chemotherapy regimen of cyclophosphamide and fludarabine will activate the subject's immune system to attack their cancer.
- Conditions
- Leukemia, Myeloid, Chronic, Lymphomas, Multiple Myeloma, Myelodysplastic Syndrome, Leukemia, Lymphocytic, Acute, Leukemia, Lymphocytic, Chronic
- Being tested
- Donor Lymphocyte Infusion, Induction Chemotherapy
- Keywords
- donor lymphocyte infusions, BMT, bone marrow transplant
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor Lymphocyte InfusionProcedure or surgery
Also called DLI
donor cells infused over 2 hrs at cell dose of 0.5 dx 10^8 CD3+T-cells/kg
Induction ChemotherapyDrug
Also called Fludara, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane
Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV
| Study group | Role | What they receive |
|---|---|---|
| CML | Active comparator | Patients with Chronic Myelogenous Leukemia (CML) who have failed or refused Gleevec(TM) therapy and will receive Donor Lymphocyte Infusion. Receives: Procedure: Donor Lymphocyte Infusion |
| Non-CML or CML that Relapsed after Donor Lymphocyte Infusion | Active comparator | Patients with non-CML or CML who have failed Donor Lymphocyte Infusion (DLI) and will receive induction chemotherapy plus DLI. Receives: Procedure: Donor Lymphocyte Infusion; Drug: Induction Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Alive
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.
Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
Measured: 1 Year
Secondary outcomes (4)
Number of Patients Alive Without Disease
The number of patients alive one year after treatment without any signs or symptoms of the cancer being treated or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
Measured: 1 Year
Number of Participants With Complete Remission
In complete remission, all signs and symptoms of cancer that can be detected with modern technology have disappeared, although cancer still may be in the body.
Measured: one year
Number of Patients With Acute Graft-Versus-Host Disease
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Measured: Day 100
Number of Patients With Bone Marrow Aplasia
Aplastic anemia is a disorder in which the bone marrow greatly decreases or stops production of blood cells.
In aplastic anemia, the basic structure of the marrow becomes abnormal, and those cells responsible for generating blood cells (hematopoietic cells) are greatly decreased in number or absent. These hematopoietic cells are replaced by large quantities of fat.
Measured: Day 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startJan 2004
- Primary completion21 Nov 2017
- Study completion24 Dec 2018
Why it stopped: Accrual Goal Met
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, ChronicStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Miller, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167180
- Sponsor's protocol ID
- 2004LS006
- Other IDs
- MT2003-15, 0401M55207
- Status last verified
- Jul 2019
- First submitted
- 9 Sep 2005
- Last updated
- 30 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Miller JS, Weisdorf DJ, Burns LJ, Slungaard A, Wagner JE, Verneris MR, Cooley S, Wangen R, Fautsch SK, Nicklow R, Defor T, Blazar BR. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone. Blood. 2007 Oct 1;110(7):2761-3. doi: 10.1182/blood-2007-05-090340. Epub 2007 Jun 19.
PubMed 17579184
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant
- ClinicalTrials.gov ID
- NCT00167180
- Acronym / sponsor ID
- 2004LS006
- Conditions
- Leukemia, Myeloid, Chronic, Lymphomas, Multiple Myeloma, Myelodysplastic Syndrome, Leukemia, Lymphocytic, Acute, Leukemia, Lymphocytic, Chronic
- Keywords
- donor lymphocyte infusions, BMT, bone marrow transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Accrual Goal Met
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jan 2004
- Primary completion
- 21 Nov 2017 (actual)
- Study completion
- 24 Dec 2018 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Posted 11 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the hypothesis that a pre-infusion preparative regimen of cyclophosphamide and fludarabine will improve the effectiveness of DLI in patients with blood cancers.
Detailed description
When cancer relapses after donor bone marrow transplantation, regular dose chemotherapy offers little hope of prolonged survival. However, there is evidence that lymphocytes can attack cancer cells. There is considerable evidence that this immune attack on cancer cells is associated with graft-versus-host disease. Although graft-versus-host disease can cause problems, this immune reaction may, in part, be the way that bone marrow transplantation cures cancer. In this study we hope that infusion of immune cells from the subject's bone marrow donor plus a chemotherapy regimen of cyclophosphamide and fludarabine will activate the subject's immune system to attack their cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CML | Active comparator | Procedure: Donor Lymphocyte InfusionPatients with Chronic Myelogenous Leukemia (CML) who have failed or refused Gleevec(TM) therapy and will receive Donor Lymphocyte Infusion. |
| Non-CML or CML that Relapsed after Donor Lymphocyte Infusion | Active comparator | Procedure: Donor Lymphocyte Infusion, Drug: Induction ChemotherapyPatients with non-CML or CML who have failed Donor Lymphocyte Infusion (DLI) and will receive induction chemotherapy plus DLI. |
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- Patients (age > or = 1 years) with a diagnosis of relapse after related or unrelated allogeneic stem cell transplantation for a hematological malignancy.
- For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least two measurements over a 6 month interval. If cytogenetics are normal and there is PCR evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of a quantitative increase in CML measured either by quantitative PCR or by fluorescent in situ hybridization (FISH).
- For non-CML, relapse will be defined based on disease specific morphologic criteria from a bone marrow biopsy and aspirate or recurrence of disease specific cytogenetics. For disease specific definition of relapse, see appendix 3. Relapse can be determined morphologically with less than 5 percent blasts if definitive relapse can be determined. Equivocal results for relapse should result in a repeated test after an appropriate time interval (suggested 1 month) to determine eligibility.
- Post-transplant lymphoproliferative diseases (often referred to as EBV-associated lymphomas) are NOT eligible for this protocol.
- For Chronic Phase CML patients only
Key exclusion criteria (5 listed)
- Concurrent signs of acute or chronic graft-versus-host disease requiring ongoing treatment at the time of relapse will be ineligible.
- Patients being treated for GVHD with prednisone, cyclosporine, Imuran or other immunosuppressive medications are not eligible until these medications are discontinued for at least 2 weeks without a flare of GVHD.
- Active CNS leukemia
- Active fungal infection or pulmonary infiltrates (stable prior treated disease is allowable)
- 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 |
|---|---|---|
| Donor Lymphocyte InfusionAlso: DLIdonor cells infused over 2 hrs at cell dose of 0.5 dx 10^8 CD3+T-cells/kg | Procedure or surgery | CML, Non-CML or CML that Relapsed after Donor Lymphocyte Infusion |
| Induction ChemotherapyAlso: Fludara, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphaneFludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV | Drug | Non-CML or CML that Relapsed after Donor Lymphocyte Infusion |
Primary outcome
Number of Patients Alive
Time frame: 1 Year
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
4 secondary outcomes
Number of Patients Alive Without Disease
Time frame: 1 Year
Number of Participants With Complete Remission
Time frame: one year
Number of Patients With Acute Graft-Versus-Host Disease
Time frame: Day 100
Number of Patients With Bone Marrow Aplasia
Time frame: Day 100
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 17579184Miller JS, Weisdorf DJ, Burns LJ, Slungaard A, Wagner JE, Verneris MR, Cooley S, Wangen R, Fautsch SK, Nicklow R, Defor T, Blazar BR. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone. Blood. 2007 Oct 1;110(7):2761-3. doi: 10.1182/blood-2007-05-090340. Epub 2007 Jun 19.
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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.
Jeffrey Miller, MD 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 Phase 2 study testing Donor Lymphocyte Infusion and Induction Chemotherapy in people with Leukemia, Myeloid, Chronic and Lymphomas, 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?
The sponsor lists 20 inclusion and 5 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: stopped early, as of the sponsor's last update on 30 Jul 2019. 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 11 Jul 2017). 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 Patients Alive (time frame: 1 Year). 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 NCT00167180, 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 30 Jul 2019.