Trial Outcomes & Findings for Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation (NCT NCT00859586)

NCT ID: NCT00859586

Last Updated: 2020-10-27

Results Overview

This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

8 participants

Primary outcome timeframe

6 months post-relapse of disease

Results posted on

2020-10-27

Participant Flow

Participant milestones

Participant milestones
Measure
Miltenyi Magnetic Cell Sorter for CD3
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Overall Study
STARTED
8
Overall Study
COMPLETED
4
Overall Study
NOT COMPLETED
4

Reasons for withdrawal

Reasons for withdrawal
Measure
Miltenyi Magnetic Cell Sorter for CD3
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Overall Study
Donors
4

Baseline Characteristics

Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=8 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
8 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
4 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
4 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
8 participants
n=5 Participants

PRIMARY outcome

Timeframe: 6 months post-relapse of disease

This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Overall Recipient Survival at 6-month Post-relapse of Disease
Recipent Survival
0 participants
Overall Recipient Survival at 6-month Post-relapse of Disease
Recipient Mortality
4 participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Overall number incidences of participants who developed Acute Graft versus Host Disease (GVHD).

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants Who Developed of Acute GVHD
2 Participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Number of participants who developed Grade I, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Grade 1 is defined as: Skin = Maculopapular rash\< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants Who Developed Grade I, Acute GVHD
1 Participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Number of participants who developed Grade II, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Stage II Acute GVHD: Skin - rash on 25-50 percent body surface area; Liver - Total Bilirubin 3.1-6.0 mg/dL; Lower GI - Diarrhea 1001-1500 mL/day. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants Who Developed Grade II, Acute GVHD
0 Participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Number of participants who developed Grade III, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Stage III Acute GVHD: Skin - Rash on \>50% of body surface; Liver - Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI - Diarrhea \> 1500 mL/day Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants Who Developed Grade III, Acute GVHD
2 Participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Number of participants who developed Grade IV, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Grade IV, Acute GVHD is defined as: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin \>15 mg/dL; Lower GI = Severe abdominal pain with or without ileus. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants Who Developed of Grade IV, Acute GVHD
0 Participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Number of incidences of participants who developed Chronic Graft vs Host Disease (GVHD). Moderate GVHD is 3 or more organs with score 1, any organ with score 2, or lung with score 1, and usually requires systemic immune-suppressive treatment. Mild disease is associated with a good prognosis whereas severe disease is associated with higher treatment-related mortality and lower survival. Organs are scored on a 0 to 3 scale from no involvement/no symptoms to severe functional compromise.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants Who Developed Chronic GVHD
0 Participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Number of participants who developed Limited Chronic Graft vs Host Disease (GVHD). Limited chronic GVHD is defined as GVHD occurring after day 100 that involved localized skin and/or mouth and/or liver.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants Who Developed Limited Chronic GVHD
0 Participants

SECONDARY outcome

Timeframe: 6 months post disease relapse

Number of participants with extensive, Chronic Graft vs Host Disease (GVHD). Extensive chronic GVHD is defined as GVHD occurring after day 100 that did not meet the definition of limited chronic GVHD.

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants With Extensive, Chronic GVHD
0 Participants

SECONDARY outcome

Timeframe: 21 Days

Number of Participants with CD3+ Engraftment who Achieved Peak Chimerism post Donor Lymphocyte Infusion (DLI)

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Participants With CD3+ Engraftment Who Achieved Peak Chimerism Post DLI
3 Participants

SECONDARY outcome

Timeframe: 21 days

Subjects experience leukemia response after partially human leukocyte antigen (HLA) matched DLI according to International Working Group criteria

Outcome measures

Outcome measures
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 Participants
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Number of Subjects Leukemia Response After Donor Lymphocyte Infusion (DLI)
0 Participants

Adverse Events

Miltenyi Magnetic Cell Sorter for CD3

Serious events: 4 serious events
Other events: 0 other events
Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure
Miltenyi Magnetic Cell Sorter for CD3
n=4 participants at risk
Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Respiratory, thoracic and mediastinal disorders
Pulmonary Insufficiency
25.0%
1/4 • Number of events 1 • Follow up for adverse events can occur up to 6 months post disease relapse
Blood and lymphatic system disorders
Bone marrow hypocellular
50.0%
2/4 • Number of events 2 • Follow up for adverse events can occur up to 6 months post disease relapse
Cardiac disorders
Cardiac Arrythmia
25.0%
1/4 • Number of events 1 • Follow up for adverse events can occur up to 6 months post disease relapse
Blood and lymphatic system disorders
Disease relapse
50.0%
2/4 • Number of events 2 • Follow up for adverse events can occur up to 6 months post disease relapse
General disorders
Multi-organ failure
50.0%
2/4 • Number of events 2 • Follow up for adverse events can occur up to 6 months post disease relapse

Other adverse events

Adverse event data not reported

Additional Information

Dr. Minoo Battiwalla

NIH NHLBI

Phone: 301-827-0939

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place