Trial Outcomes & Findings for Donor Lymphocyte Infusion (DLI) of T-cells Genetically Modified With iCasp9 Suicide Gene (NCT NCT01875237)

Last Updated: 2019-07-16

Results Overview

To evaluate the safety of the infusion of inducible caspase 9 (BPZ-1001) modified T-cells followed by dimerizer drug, AP1903. Safety evaluated by number of participants with Adverse events.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

3 participants

Primary outcome timeframe

up to 3.5 years

Results posted on

2019-07-16

Participant Flow

patient with hematologic malignancies receiving allogeneic hematopoietic transplants.

patients who do not have GVHD on day 42 receive genetically modified donor lymphocytes with suicide gene to be activated by drug AP1903 if GVHD occurs.

Participant milestones

Participant milestones
Measure	Transplant Only Patients who did not move forward to DLI	Transplat Plus DLI Proceeded to DLI per protocol
Overall Study STARTED	2	1
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Transplant Only Patients who did not move forward to DLI	Transplat Plus DLI Proceeded to DLI per protocol
Overall Study GVDH before DLI	1	0
Overall Study DLI cells could not be produced	1	0

Baseline Characteristics

Donor Lymphocyte Infusion (DLI) of T-cells Genetically Modified With iCasp9 Suicide Gene

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Transplant Only n=2 Participants Patients who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol	Total n=3 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants

PRIMARY outcome

Timeframe: up to 3.5 years

Population: Participant who received Donor Lymphocyte infusion and AP 1903

To evaluate the safety of the infusion of inducible caspase 9 (BPZ-1001) modified T-cells followed by dimerizer drug, AP1903. Safety evaluated by number of participants with Adverse events.

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
To Evaluate the Safety of Donor Lymphocyte Infusion Followed by Dimerizer Drug, AP1903 by Number of Participants With Adverse Events.	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Transplant only participants did not receive DLI.

Participants to assess at 6 months post donor lymphocyte infusion (DLI): disease-free survival \& non-relapse mortality, chimerism and GVHD

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
Number of Participants Assessed Post Donor Lymphocyte Infusion (DLI): Disease-free Survival & Non-relapse Mortality, Chimerism and GVHD. disease-free survivaI	0 Participants	1 Participants
Number of Participants Assessed Post Donor Lymphocyte Infusion (DLI): Disease-free Survival & Non-relapse Mortality, Chimerism and GVHD. chimerism post DLI	0 Participants	1 Participants
Number of Participants Assessed Post Donor Lymphocyte Infusion (DLI): Disease-free Survival & Non-relapse Mortality, Chimerism and GVHD. GVHD post DLI	0 Participants	1 Participants
Number of Participants Assessed Post Donor Lymphocyte Infusion (DLI): Disease-free Survival & Non-relapse Mortality, Chimerism and GVHD. non-relapse mortality	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 year

Population: all patients who received DLI

To assess the incidence of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder or EBV reactivation requiring therapy post DLI.

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
To Assess the Incidence of Epstein-Barr Virus -PTLD or EBV Reactivation Requiring Therapy Post DLI.	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 28, 56, and 180 post DLI.

Population: all patients who received DLI

To assess the proportion of patients developing grade I-IV acute GvHD by Day 28, 56, and 180 post DLI.

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
To Assess the Proportion of Patients Developing Grade I-IV Acute GvHD Day 28	0 Participants	1 Participants
To Assess the Proportion of Patients Developing Grade I-IV Acute GvHD Day 56	0 Participants	1 Participants
To Assess the Proportion of Patients Developing Grade I-IV Acute GvHD Day 180	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 3, 7, 14, 28, and 56 post-administration of AP1903

Population: Patient who received DLI

To assess the proportions of GvHD complete response (CR), partial response (PR), mixed response, no response, and progression among surviving patients at Day 3, 7, 14, 28, and 56 post-administration of AP1903.

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 3 post-administration of AP1903 · complete response	0 Participants	1 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 3 post-administration of AP1903 · partial response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 3 post-administration of AP1903 · no response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 3 post-administration of AP1903 · progression	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 7 post-administration of AP1903 · complete response	0 Participants	1 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 7 post-administration of AP1903 · partial response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 7 post-administration of AP1903 · no response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 7 post-administration of AP1903 · progression	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 14 post-administration of AP1903 · complete response	0 Participants	1 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 14 post-administration of AP1903 · partial response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 14 post-administration of AP1903 · no response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 14 post-administration of AP1903 · progression	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 28 post-administration of AP1903 · complete response	0 Participants	1 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 28 post-administration of AP1903 · partial response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 28 post-administration of AP1903 · no response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 28 post-administration of AP1903 · progression	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 56 post-administration of AP1903 · complete response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 56 post-administration of AP1903 · partial response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 56 post-administration of AP1903 · no response	0 Participants	0 Participants
To Assess the Proportions of GvHD Response Post-administration of AP1903. Day 56 post-administration of AP1903 · progression	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 3, 7, 14, 28, and 56 post-administration of AP1903.

Population: Patient who received AP1903

To assess the incidence of GvHD treatment failure, defined as no response, progression, administration of additional therapy for GvHD, or mortality post-administration of AP1903.

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
To Assess the Incidence of GvHD Treatment Failure Post-administration of AP1903. Day 3 post-administration of AP1903.	0 Participants	1 Participants
To Assess the Incidence of GvHD Treatment Failure Post-administration of AP1903. Day 7 post-administration of AP1903.	0 Participants	1 Participants
To Assess the Incidence of GvHD Treatment Failure Post-administration of AP1903. Day 14 post-administration of AP1903.	0 Participants	1 Participants
To Assess the Incidence of GvHD Treatment Failure Post-administration of AP1903. Day 28 post-administration of AP1903.	0 Participants	1 Participants
To Assess the Incidence of GvHD Treatment Failure Post-administration of AP1903. Day 56 post-administration of AP1903.	0 Participants	1 Participants

SECONDARY outcome

Timeframe: before Day 56 post AP1903

Population: Patients who received AP1903

To assess participants with incidence of acute GvHD flare after CR/PR requiring additional agent (including 2.5 mg/kg/day of prednisone \[or methylprednisolone equivalent of 2 mg/kg/day\]) for systemic therapy before Day 56 post-administration of AP1903."

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
To Assess the Incidence of Acute GvHD Flare After CR/PR Requiring Additional Agent for Systemic Therapy Before Day 56 Post-administration of AP1903.	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 6 months

Population: patients who received DLI

To assess the number of Participants with 100% donor chimerism at 6 months post donor lymphocyte infusion (DLI)

Outcome measures

Outcome measures
Measure	Transplant Only Participants who did not move forward to DLI	Transplat Plus DLI n=1 Participants Proceeded to DLI per protocol
To Assess Post Donor Lymphocyte Infusion (DLI) Chimerism	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Population: Patient who received DLI was removed from study prior to 6 month time frame. No outcome measure was provided.

To assess at 6 months post donor lymphocyte infusion (DLI): GVHD grade \& time to resolution

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 56 post administration of AP1903

Population: Participant completed quality of life surveys but data was not analyzed to provide outcome measure.

To determine the change in patient-reported outcomes from enrollment to day 56 post administration of AP1903, through the patient quality of life survey.

Outcome measures

Outcome data not reported

Adverse Events

Transplant Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Transplat Plus DLI

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Transplant Only Patients who did not move forward to DLI	Transplat Plus DLI n=1 participants at risk Proceeded to DLI per protocol
Infections and infestations Infection	— 0/0 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.	100.0% 1/1 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.

Other adverse events

Other adverse events
Measure	Transplant Only Patients who did not move forward to DLI	Transplat Plus DLI n=1 participants at risk Proceeded to DLI per protocol
Renal and urinary disorders Elevated creatinine	— 0/0 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.	100.0% 1/1 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.
Infections and infestations Infection (CMV)	— 0/0 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.	100.0% 1/1 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.
Infections and infestations Infection (adenovirus)	— 0/0 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.	100.0% 1/1 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.
Infections and infestations Infection (E.Coli)	— 0/0 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.	100.0% 1/1 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.
Gastrointestinal disorders Nausea	— 0/0 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.	100.0% 1/1 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.
Skin and subcutaneous tissue disorders Skin Rash	— 0/0 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.	100.0% 1/1 • up to 30 days after DLI or after AP1903 infusion, whichever is later Adverse events were captured for patients who received DLI and AP1903.

Additional Information

Champlin,Richard,M.D. / Stem Cell Transplantation

UT MD Anderson Cancer Center

Phone: 713-792-8750

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place