Donor Lymphocyte Infusion in Treating Patients With Recurrent or Persistent Hematologic Cancer After Donor Stem Cell Transplant

Sponsor
Roswell Park Cancer Institute (Other)
Overall Status
Completed
CT.gov ID
NCT00534118
Collaborator
(none)
39
1
1
177.8
0.2

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
  • Biological: donor lymphocytes
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

Study Type:
Interventional
Actual Enrollment :
39 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Cellular Infusions in Patients With Recurrent or Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplant
Actual Study Start Date :
Oct 1, 2003
Actual Primary Completion Date :
Jul 26, 2018
Actual Study Completion Date :
Jul 26, 2018

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

  1. Complete Remission Rate [100 days post DLI]

    continued or induced complete remission after DLI

  2. 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

  1. 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

Ages Eligible for Study:
N/A to 76 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00534118
Other Study ID Numbers:
  • CDR0000564827
  • RPCI-I-00703
First Posted:
Sep 24, 2007
Last Update Posted:
Aug 26, 2020
Last Verified:
Aug 1, 2020
Keywords provided by Roswell Park Cancer Institute
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Primary Outcome
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
3. Secondary Outcome
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

[Not Specified]

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
Email theresa.hahn@roswellpark.org
Responsible Party:
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00534118
Other Study ID Numbers:
  • CDR0000564827
  • RPCI-I-00703
First Posted:
Sep 24, 2007
Last Update Posted:
Aug 26, 2020
Last Verified:
Aug 1, 2020