Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 1/2NCT00068718
Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant
A Phase 1/2 study testing Therapeutic Allogeneic Lymphocytes in people with Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Recurrent Adult Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 4 sites in 3 countries.
Trial summary
This phase I/II trial studies the side effects of donor lymphocyte infusion and to see how well it works in treating patients with persistent, relapsed (disease that has returned), or progressing cancer after donor hematopoietic cell transplantation. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia
- What is being tested?
- Therapeutic Allogeneic Lymphocytes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 4 sitesin 3 countries
- Study dates
- May 2003to Apr 2013
- Phase
- Phase 1/2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Only patients having received a preceding nonmyeloablative allogeneic transplantation with fludarabine/2 Gy total-body irradiation (TBI) - 4 Gy TBI or 2 Gy TBI - 4 Gy TBI conditioning from either a related or unrelated donor are eligible for this protocol
- Patients with persistent, relapsed or progressing malignancy after nonmyeloablative allogeneic transplantation; persistent disease will be defined as a failure to achieve a response as compared to baseline
- Patients with rapidly progressing malignancies (acute myeloid leukemia [AML], acute lymphocytic leukemia [ALL], blastic phase chronic myelogenous leukemia [CML-BC] intermediate-high-grade non-Hodgkin lymphoma [NHL], Hodgkin's lymphoma or aggressive multiple myeloma [MM]) should receive salvage chemotherapy or radiation before DLI according to the recommendation made in this protocol; any form of salvage chemotherapy should be discontinued no less than 3 weeks before DLI; therapy with Gleevec or interferon (IFN)-alpha should be discontinued prior to DLI; after salvage chemotherapy restaging is performed, patients with progressive disease and patients not meeting the inclusion criteria of the study after chemotherapy will be excluded from the study; patients are allowed to receive further doses of chemotherapy after DLI administration if they are scheduled for further DLI; after additional therapy the patients must be restaged and must again meet inclusion criteria to receive further DLI
- Patients must be able to tolerate a taper of systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day; all other immunosuppressive therapy must have been discontinued for at least two weeks without significant flares in GVHD (i.e., increase of acute GVHD by one or more grades)
- Patients must have persistent donor cluster of differentiation (CD)3 cells (> 5% donor CD3 cells by a deoxyribonucleic acid [DNA]-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP] [or fluorescent in situ hybridization (FISH) studies or variable number tandem repeat (VNTR)])
- DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected cryopreserved peripheral blood stem cells (PBSC) after mobilization with granulocyte colony-stimulating factor (G-CSF) or cryopreserved unmodified leukapheresis product from the original donor can be used; if cryopreserved product is not available, the DLI product must be from the original donor of hematopoietic cell transplantation
Show all 10Show fewer
- DONOR: Original donor of hematopoietic cell transplantation
- DONOR: Donor must give consent to leukapheresis
- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian)
- DONOR: Donor must be medically fit to undergo the apheresis procedure (institutional guidelines for apheresis)
Who cannot join
- Current grade II to IV acute GVHD or extensive chronic GVHD
- Karnofsky score < 50%
- Lansky Play-Performance Score < 40 for pediatric patients
- DONOR: Donors who are not suitable for medical reasons to donate peripheral blood mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the American Association of Blood Banks (AABB)
- DONOR: Pregnancy
- DONOR: Human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection
- DONOR: Recent immunization may require a delay
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
United States2 sites
VA Puget Sound Health Care System
Seattle, Washington, 98101
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Donor Lymphocyte Infusion for the Treatment of Malignancy After Hematopoietic Cell Transplantation Using Nonmyeloablative Conditioning - A Multi-center Trial
This phase I/II trial studies the side effects of donor lymphocyte infusion and to see how well it works in treating patients with persistent, relapsed (disease that has returned), or progressing cancer after donor hematopoietic cell transplantation. White blood cells from donors may be able to kill cancer cells in patients with cancer that has come back (recurrent) after a donor hematopoietic cell transplant.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety of donor lymphocyte infusion (DLI) as adoptive immunotherapy for persistent or relapsed malignant diseases in patients after related or unrelated nonmyeloablative transplantation.
SECONDARY OBJECTIVES:
- To determine disease response, progression free and overall survival, chimerism, grade of graft-versus-host disease (GVHD), and infections.
OUTLINE:
Patients undergo unirradiated DLI over 15-30 minutes on day 0. Patients then undergo restaging on day 28 and may undergo a second DLI after at least 4 weeks if no significant GVHD develops and disease status worsens or after at least 8 weeks if disease status is unchanged and persistent donor T-cells are documented.
After completion of study treatment, patients are followed up periodically.
- Conditions
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Plasma Cell Myeloma
- Being tested
- Therapeutic Allogeneic Lymphocytes
- Medical subject headings
- Blast Crisis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Hodgkin Disease, Lymphoma, Non-Hodgkin, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Therapeutic Allogeneic LymphocytesBiological
Also called Allogeneic Lymphocytes
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (DLI) | Experimental | Patients undergo unirradiated DLI over 15-30 minutes on day 0. Patients then undergo restaging on day 28 and may undergo a second DLI after at least 4 weeks if no significant GVHD develops and disease status worsens or after at least 8 weeks if disease status is unchanged and persistent donor T-cells are documented. Receives: Biological: Therapeutic Allogeneic Lymphocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD
Percentage of Participants with Grade IV Acute GVHD
Measured: 100 days after DLI
Secondary outcomes (6)
Incidence of Graft Rejection
Percentage patients with graft rejection.
Measured: 100 days after DLI
Incidence of Relapse/Progression
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever >38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%.
CMML, AML, ALL >30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia.
CLL ≥1 of: Physical exam/imaging studies ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation.
NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions.
MM
≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
Measured: 1 year after DLI
Incidence of Grade II-IV GVHD in Patients Undergoing DLI Following a Non-myeloablative Transplant
Percentage of Participants with II-IV Acute GVHD
Measured: 100 days after DLI
Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant
Percentage of Participants with infections.
Measured: 100 days after DLI
Overall Survival
Percentage patients surviving 1 year post-transplant.
Measured: 1 year after DLI
Progression-free Survival
Percentage of patients with progression-free survival
Measured: 1 year after DLI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2003 (estimated)
- Study startMay 2003
- Primary completionApr 2013
- Study completionApr 2013
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 Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Brenda Sandmaier, Fred Hutchinson Cancer Center
- Investigators
- Brenda Sandmaier, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00068718
- Sponsor's protocol ID
- 1803.00
- Other IDs
- NCI-2010-00163, 1803.00, P01CA078902, P30CA015704
- Status last verified
- Jan 2020
- First submitted
- 10 Sep 2003
- Last updated
- 31 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donor Lymphocyte Infusion for the Treatment of Malignancy After Hematopoietic Cell Transplantation Using Nonmyeloablative Conditioning - A Multi-center Trial
- ClinicalTrials.gov ID
- NCT00068718
- Acronym / sponsor ID
- 1803.00
- Conditions
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Plasma Cell Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2003 (actual)
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 11 Sep 2003 (estimated)
- Results
- Posted 10 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial studies the side effects of donor lymphocyte infusion and to see how well it works in treating patients with persistent, relapsed (disease that has returned), or progressing cancer after donor hematopoietic cell transplantation. White blood cells from donors may be able to kill cancer cells in patients with cancer that has come back (recurrent) after a donor hematopoietic cell transplant.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety of donor lymphocyte infusion (DLI) as adoptive immunotherapy for persistent or relapsed malignant diseases in patients after related or unrelated nonmyeloablative transplantation.
SECONDARY OBJECTIVES:
- To determine disease response, progression free and overall survival, chimerism, grade of graft-versus-host disease (GVHD), and infections.
OUTLINE:
Patients undergo unirradiated DLI over 15-30 minutes on day 0. Patients then undergo restaging on day 28 and may undergo a second DLI after at least 4 weeks if no significant GVHD develops and disease status worsens or after at least 8 weeks if disease status is unchanged and persistent donor T-cells are documented.
After completion of study treatment, patients are followed up periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (DLI) | Experimental | Biological: Therapeutic Allogeneic LymphocytesPatients undergo unirradiated DLI over 15-30 minutes on day 0. Patients then undergo restaging on day 28 and may undergo a second DLI after at least 4 weeks if no significant GVHD develops and disease status worsens or after at least 8 weeks if disease status is unchanged and persistent donor T-cells are documented. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Only patients having received a preceding nonmyeloablative allogeneic transplantation with fludarabine/2 Gy total-body irradiation (TBI) - 4 Gy TBI or 2 Gy TBI - 4 Gy TBI conditioning from either a related or unrelated donor are eligible for this protocol
- Patients with persistent, relapsed or progressing malignancy after nonmyeloablative allogeneic transplantation; persistent disease will be defined as a failure to achieve a response as compared to baseline
- Patients with rapidly progressing malignancies (acute myeloid leukemia [AML], acute lymphocytic leukemia [ALL], blastic phase chronic myelogenous leukemia [CML-BC] intermediate-high-grade non-Hodgkin lymphoma [NHL], Hodgkin's lymphoma or aggressive multiple myeloma [MM]) should receive salvage chemotherapy or radiation before DLI according to the recommendation made in this protocol; any form of salvage chemotherapy should be discontinued no less than 3 weeks before DLI; therapy with Gleevec or interferon (IFN)-alpha should be discontinued prior to DLI; after salvage chemotherapy restaging is performed, patients with progressive disease and patients not meeting the inclusion criteria of the study after chemotherapy will be excluded from the study; patients are allowed to receive further doses of chemotherapy after DLI administration if they are scheduled for further DLI; after additional therapy the patients must be restaged and must again meet inclusion criteria to receive further DLI
- Patients must be able to tolerate a taper of systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day; all other immunosuppressive therapy must have been discontinued for at least two weeks without significant flares in GVHD (i.e., increase of acute GVHD by one or more grades)
- Patients must have persistent donor cluster of differentiation (CD)3 cells (> 5% donor CD3 cells by a deoxyribonucleic acid [DNA]-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP] [or fluorescent in situ hybridization (FISH) studies or variable number tandem repeat (VNTR)])
Key exclusion criteria (7 listed)
- Current grade II to IV acute GVHD or extensive chronic GVHD
- Karnofsky score < 50%
- Lansky Play-Performance Score < 40 for pediatric patients
- DONOR: Donors who are not suitable for medical reasons to donate peripheral blood mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the American Association of Blood Banks (AABB)
- DONOR: Pregnancy
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 |
|---|---|---|
| Therapeutic Allogeneic LymphocytesAlso: Allogeneic LymphocytesGiven IV | Biological | Treatment (DLI) |
Primary outcome
Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD
Time frame: 100 days after DLI
Percentage of Participants with Grade IV Acute GVHD
6 secondary outcomes
Incidence of Graft Rejection
Time frame: 100 days after DLI
Incidence of Relapse/Progression
Time frame: 1 year after DLI
Incidence of Grade II-IV GVHD in Patients Undergoing DLI Following a Non-myeloablative Transplant
Time frame: 100 days after DLI
Incidence of Infections in Patients Undergoing DLI Following a Non-myeloablative Transplant
Time frame: 100 days after DLI
Overall Survival
Time frame: 1 year after DLI
Progression-free Survival
Time frame: 1 year after DLI
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
Active, not recruitingPhase 2
Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia
Active, not recruitingPhase 1/2
Bosutinib in Pediatric Patients With Newly Diagnosed Chronic Phase or Resistant/Intolerant Ph + Chronic Myeloid Leukemia
Philadelphia Chromosome Positive CML, Accelerated Phase Chronic Myelogenous Leukemia
RecruitingPhase 1
Edetate Calcium Disodium or Succimer in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Chemotherapy
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Active, not recruitingPhase 1
Hu8F4 in Treating Patients With Advanced Hematologic Malignancies
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
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.
Brenda Sandmaier principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Therapeutic Allogeneic Lymphocytes in people with Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Recurrent Adult Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 4 sites in 3 countries.
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 10 inclusion and 7 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: finished, as of the sponsor's last update on 31 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Germany, Italy. 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 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?
Yes. Results are posted in the registry (first posted 10 Mar 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?
Safety of DLI Following a Non-myeloablative Transplant, Defined as Incidence of Grade IV Acute GVHD (time frame: 100 days after DLI). 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 31 Jan 2020.