Donor Lymphocyte Infusion in Treating Patients With Recurrent or Persistent Hematologic Cancer After Donor Stem Cell Transplant
Study Details
Study Description
Brief Summary
RATIONALE: Giving an infusion of donor lymphocytes may be able to kill cancer cells in patients with hematologic cancer that has come back after a donor stem cell transplant.
PURPOSE: This clinical trial is studying how well donor lymphocyte infusion works in treating patients with recurrent or persistent hematologic cancer after donor stem cell transplant.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
N/A |
Detailed Description
OBJECTIVES:
Primary
- Determine if the complete response rate exceeds 10% in patients with recurrent or persistent hematologic malignancies treated with donor lymphocyte infusion.
Secondary
-
Estimate the complete response rate in these patients.
-
Assess the toxicity of donor lymphocyte infusion in these patients.
OUTLINE: Patients receive up to four donor lymphocyte infusions at least 1 month apart in the absence of disease progression, unacceptable toxicity, or uncontrolled graft-versus-host disease.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Infusion Patients receive up to four donor lymphocyte infusions at least 1 month apart in the absence of disease progression, unacceptable toxicity, or uncontrolled graft-versus-host disease |
Biological: donor lymphocytes
Given IV
|
Outcome Measures
Primary Outcome Measures
- Complete Remission Rate [100 days post DLI]
continued or induced complete remission after DLI
- Duration of Complete Response in Months (Maximum 12) [1 year post DLI]
For participants who achieve a complete remission after DLI, the duration of time until 1) relapse or 2) death in remission or 3) subsequent DLI or 4) last followup (at 1 year after DLI)
Secondary Outcome Measures
- Acute Graft-versus-host Disease [100 days post DLI]
development of grade III-IV acute graft-versus-host disease (GVHD) per Glucksberg criteria
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Has undergone allogeneic stem cell transplantation (ASCT) for hematologic malignancy at least 30 days ago
-
No failure to engraft following transplant
-
No active acute or chronic graft-versus-host disease (GVHD)
-
Minimal GVHD allowed
-
Persistent or relapsed disease after ASCT, including 1 of the following:
-
Chronic myelogenous leukemia (CML), meeting any of the following criteria:
-
Molecular relapse (may be treated with imatinib mesylate after transplant), as defined by any of the following:
-
ASCT was non-T-cell depleted, a negative bcr/abl was documented by PCR post-transplant, and bcr/abl is now detectable by 2 consecutive PCR determinations > 30 days apart
-
ASCT was non-T-cell depleted and bcr/abl is detectable by PCR at any time after day 180 post-transplant
-
Cytogenetic relapse after 3-6 months of imatinib mesylate
-
Relapsed chronic phase, accelerated phase, or blastic phase CML after 3-6 months of imatinib mesylate
-
Must currently be in chronic phase or accelerated phase CML only
-
Patients with blastic phase CML must attain a second chronic phase
-
Acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes, meeting any of the following criteria:
-
Molecular relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific molecular abnormality detectable by PCR
-
Cytogenetic relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific chromosome abnormality detectable by standard cytogenetics at any time after day 60 post-transplant
-
Hematologic relapse, as evidenced by > 20% blasts in bone marrow or soft tissue recurrence
-
Must be treated with chemotherapy after transplant, but before study donor lymphocyte infusion (DLI)
-
Multiple myeloma
-
Relapsed disease or recurrence of M-protein after thalidomide or other salvage treatment
-
Prior post-transplant documentation of disappearance of M-protein by immunofixation
-
Residual or progressive disease
-
Rising M-protein level at any time post-transplant (measured at 3-month intervals)
-
Original M-protein detectable at 6 months post-transplant
-
Immune protein electrophoresis (IPEP) is required to show that M-component is the same on day 60 post-transplant as pre-transplant
-
Residual (> 5%) plasma cells in bone marrow
-
Relapsed non-Hodgkin lymphoma or Hodgkin lymphoma
-
Relapse or progression of disease must be evidenced within 3 months prior to donor lymphocyte infusion by physical exam, radiographic studies, or molecular studies
-
Tumor should be re-biopsied to determine histology
-
If Epstein-Barr virus (EBV) lymphoma is suspected, peripheral blood must be assayed for EBV genome (i.e., EBV DNA testing by PCR) within the past 30 days
-
EBV infection with associated pancytopenia
-
Persistent or refractory pancytopenia with EBV genome detected by PCR in the peripheral blood
-
Refractory pancytopenia is defined as pancytopenia that is poorly responsive to growth factors and/or transfusions
-
EBV lymphoproliferative disorder
-
Clonal lymphadenopathy that is refractory to standard therapy with acyclovir and immunoglobulin (DLI may be given with rituximab)
-
Not a candidate for repeat ASCT
-
Chimerism status is not required for determining eligibility for DLI
-
Patients eligible for allogeneic ASCT, but for whom DLI is offered as the first option, should have full donor chimerism at relapse or after therapy for relapsed disease
-
Patients with relapsed underlying disease after transplant who achieved remission after chemotherapy are allowed
-
No CNS recurrence that is not cleared by standard chemotherapy
-
CNS remission status must be maintained for 2 weeks
-
Original hematopoietic progenitor stem cell donor must be available for cell donation
-
No syngeneic donors
PATIENT CHARACTERISTICS:
-
Karnofsky performance status 60-100%
-
Life expectancy ≥ 8 weeks
-
Creatinine < 3 mg/dL
-
ABO/Rh and CMV IgG/IgM status known
-
No HIV1 and HIV2 antibody
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception during and for 3 months (males) or 6 months (females) after completion of study treatment
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263-0001 |
Sponsors and Collaborators
- Roswell Park Cancer Institute
Investigators
- Principal Investigator: Philip L. McCarthy, MD, Roswell Park Cancer Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- CDR0000564827
- RPCI-I-00703
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Multiple DLI | Single DLI |
---|---|---|
Arm/Group Description | Accruals where the patient received 2-4 donor lymphocyte infusions Arm includes total number of infusions | accruals where the patient received only one donor lymphocyte infusion |
Period Title: Overall Study | ||
STARTED | 17 | 22 |
COMPLETED | 17 | 22 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Multiple DLI | Single DLI | Total |
---|---|---|---|
Arm/Group Description | Accruals where the patient received 2-4 donor lymphocyte infusions Arm includes total number of infusions | Accruals where the patient received only one donor lymphocyte infusion | Total of all reporting groups |
Overall Participants | 15 | 12 | 27 |
Age (Count of Participants) | |||
<=18 years |
1
6.7%
|
1
8.3%
|
2
7.4%
|
Between 18 and 65 years |
12
80%
|
9
75%
|
21
77.8%
|
>=65 years |
2
13.3%
|
2
16.7%
|
4
14.8%
|
Age (years) [Median (Full Range) ] | |||
Median (Full Range) [years] |
45
|
53.5
|
51
|
Sex: Female, Male (Count of Participants) | |||
Female |
5
33.3%
|
2
16.7%
|
7
25.9%
|
Male |
10
66.7%
|
10
83.3%
|
20
74.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
Not Hispanic or Latino |
15
100%
|
12
100%
|
27
100%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
1
6.7%
|
0
0%
|
1
3.7%
|
Asian |
1
6.7%
|
0
0%
|
1
3.7%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
0%
|
0
0%
|
White |
13
86.7%
|
12
100%
|
25
92.6%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||
United States |
15
100%
|
12
100%
|
27
100%
|
Disease (Count of Participants) | |||
Acute Myeloid Leukemia |
8
53.3%
|
9
75%
|
17
63%
|
Myelodysplastic Syndrome |
2
13.3%
|
0
0%
|
2
7.4%
|
Non Hodgkin Leukemia |
2
13.3%
|
1
8.3%
|
3
11.1%
|
Acute Lymphoblastic Leukemia |
1
6.7%
|
0
0%
|
1
3.7%
|
Chronic Myeloid Leukemia |
1
6.7%
|
1
8.3%
|
2
7.4%
|
Hodgkin Lymphoma |
1
6.7%
|
0
0%
|
1
3.7%
|
Prolymphocytic Leukemia |
0
0%
|
1
8.3%
|
1
3.7%
|
Outcome Measures
Title | Complete Remission Rate |
---|---|
Description | continued or induced complete remission after DLI |
Time Frame | 100 days post DLI |
Outcome Measure Data
Analysis Population Description |
---|
Each accrual is evaluable independently, some patients in both the Multiple and Single DLI are accrued more than once; total unique patients in multiple DLI is 15 and in single DLI is 12 |
Arm/Group Title | Multiple DLI | Single DLI |
---|---|---|
Arm/Group Description | Accruals where the patient received 2-4 donor lymphocyte infusions Arm includes total number of infusions | accruals where the patient received only one donor lymphocyte infusion |
Measure Participants | 17 | 22 |
Count of Participants [Participants] |
8
53.3%
|
6
50%
|
Title | Duration of Complete Response in Months (Maximum 12) |
---|---|
Description | For participants who achieve a complete remission after DLI, the duration of time until 1) relapse or 2) death in remission or 3) subsequent DLI or 4) last followup (at 1 year after DLI) |
Time Frame | 1 year post DLI |
Outcome Measure Data
Analysis Population Description |
---|
Accruals which achieved a continued or induced complete remission at Day +100 after DLI, patients are censored at death in remission or at time of subsequent DLI |
Arm/Group Title | Multiple DLI - Complete Responders | Single DLI - Complete Responders |
---|---|---|
Arm/Group Description | Duration of time patients who achieved a complete remission by day +100 after DLI maintained that remission | Duration of time patients who achieved a complete remission by day +100 after DLI maintained that remission |
Measure Participants | 8 | 6 |
Median (Full Range) [months] |
10.1
|
9
|
Title | Acute Graft-versus-host Disease |
---|---|
Description | development of grade III-IV acute graft-versus-host disease (GVHD) per Glucksberg criteria |
Time Frame | 100 days post DLI |
Outcome Measure Data
Analysis Population Description |
---|
Each accrual is evaluable for acute GVHD grade III-IV |
Arm/Group Title | Multiple DLI | Single DLI |
---|---|---|
Arm/Group Description | Accruals where the patient received 2-4 donor lymphocyte infusions Arm includes total number of infusions | accruals where the patient received only one donor lymphocyte infusion |
Measure Participants | 17 | 22 |
Count of Participants [Participants] |
0
0%
|
4
33.3%
|
Adverse Events
Time Frame | All cause mortality includes individual participants who experienced death due to any cause before 3 years after first DLI and is the only SAE/AE captured per protocol | |||
---|---|---|---|---|
Adverse Event Reporting Description | All cause mortality includes individual participants who experienced death due to any cause before 3 years after first DLI | |||
Arm/Group Title | Multiple DLI | Single DLI | ||
Arm/Group Description | Accruals where the patient received 2-4 donor lymphocyte infusions Arm includes total number of infusions | accruals where the patient received only one donor lymphocyte infusion | ||
All Cause Mortality |
||||
Multiple DLI | Single DLI | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/15 (66.7%) | 7/12 (58.3%) | ||
Serious Adverse Events |
||||
Multiple DLI | Single DLI | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/15 (66.7%) | 7/12 (58.3%) | ||
General disorders | ||||
All cause mortality by 3 years after first DLI | 10/15 (66.7%) | 10 | 7/12 (58.3%) | 7 |
Other (Not Including Serious) Adverse Events |
||||
Multiple DLI | Single DLI | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/15 (0%) | 0/12 (0%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Theresa Hahn |
---|---|
Organization | Roswell Park Cancer Institute |
Phone | 716-845-2300 |
theresa.hahn@roswellpark.org |
- CDR0000564827
- RPCI-I-00703