Trial Outcomes & Findings for Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation (NCT NCT02458235)

Last Updated: 2020-10-12

Results Overview

Relapse rate will be estimated using a percentage of participants who relapsed. It is assumed that the rate of relapse in pediatric acute leukemia post-transplant would be 40%, azacitidine +/- Donor Lymphocyte Infusion (DLI) would reduce the 2-year relapse rate by approximately 40% to a rate of 25%.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2020-10-12

Participant Flow

Participant milestones

Participant milestones
Measure	Azacitidine/Donor Lymphocyte Infusion Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Overall Study STARTED	17
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Donor Lymphocyte Infusion With Azacitidine to Prevent Hematologic Malignancy Relapse After Stem Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Age, Customized 0-9 years	7 Participants n=5 Participants
Age, Customized 10-19 years	9 Participants n=5 Participants
Age, Customized 20-29 years	1 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Relapse Rate	23.5 percentage of participants

PRIMARY outcome

Timeframe: Up to 2 years

Frequency of system specific adverse events of interest include renal, hepatic, cardiac, pulmonary, or neurologic toxicities. Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Frequency of System Specific Grade 3 or Higher Treatment-related Adverse Events	0 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Proportion of participants with Grade 3-4 acute GVHD and moderate to severe chronic GVHD will be reported.

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Proportion of Participants With Acute and Chronic Graft Versus Host Disease (GVHD) Acute GVHD	0.176 proportion of participants
Proportion of Participants With Acute and Chronic Graft Versus Host Disease (GVHD) Moderate to severe chronic GVHD	0.411 proportion of participants

PRIMARY outcome

Timeframe: Up to 2 years

The proportion of participants will be reported for Grade 3-4 invasive fungal infection or disease caused by viral infections

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Proportion of Participants With Serious Infection	0.41 proportion of participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: No participants experienced a severe hematologic toxicity including graft failure

The proportion of participants will be reported for Grade 4 severe hematologic toxicities including graft failure

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Proportion of Participants With Severe Hematologic Toxicity Including Graft Failure	0.00 proportion of participants

PRIMARY outcome

Timeframe: Up to 2 years

The number of participants whom had greater than 2 dose reductions for any reason.

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Number of Participants Whom Had >2 Dose Reductions for Any Reason	0 participants

SECONDARY outcome

Timeframe: Up to 2 years

Release-free survival rate is defined as the median length of time after beginning treatment that the participant survives without progression or relapse, reported in months

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Median Relapse-free Survival	22 months Interval 1.0 to 24.0

SECONDARY outcome

Timeframe: Up to 2 years

Time to relapse is defined as the length of time after beginning treatment until the participant has experienced a relapse in disease, measured in months.

Outcome measures

Outcome measures
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 Participants Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Median Time to Relapse	3 months Interval 1.0 to 17.0

Adverse Events

Azacitidine/Donor Lymphocyte Infusion

Serious events: 10 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 participants at risk Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.9% 1/17 • Number of events 1 • Up to 2 years
Immune system disorders Immune system disorders - Other	17.6% 3/17 • Number of events 3 • Up to 2 years
General disorders Fever	5.9% 1/17 • Number of events 1 • Up to 2 years
Infections and infestations Infections and infestations - Other	5.9% 1/17 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	5.9% 1/17 • Number of events 1 • Up to 2 years
General disorders Edema face	5.9% 1/17 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Diarrhea	5.9% 1/17 • Number of events 1 • Up to 2 years
Cardiac disorders Cardiac disorders - Other	5.9% 1/17 • Number of events 1 • Up to 2 years
Investigations Platelet count decreased	5.9% 1/17 • Number of events 1 • Up to 2 years
Hepatobiliary disorders Hepatobiliary disorders - Other	5.9% 1/17 • Number of events 1 • Up to 2 years
Investigations Elevated transaminases	5.9% 1/17 • Number of events 1 • Up to 2 years

Other adverse events

Other adverse events
Measure	Azacitidine/Donor Lymphocyte Infusion n=17 participants at risk Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle.
Investigations Acute GVHD	17.6% 3/17 • Number of events 3 • Up to 2 years
Endocrine disorders Adrenal insufficiency	17.6% 3/17 • Number of events 3 • Up to 2 years
Eye disorders Anisocoria	5.9% 1/17 • Number of events 1 • Up to 2 years
Psychiatric disorders Anxiety	5.9% 1/17 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders Avascular necrosis	5.9% 1/17 • Number of events 1 • Up to 2 years
Infections and infestations Bacteremia	5.9% 1/17 • Number of events 1 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.9% 1/17 • Number of events 1 • Up to 2 years
General disorders Chest pain	5.9% 1/17 • Number of events 1 • Up to 2 years
Hepatobiliary disorders Cholestatic liver disease	5.9% 1/17 • Number of events 1 • Up to 2 years
Investigations Chronic GVHD	41.2% 7/17 • Number of events 7 • Up to 2 years
General disorders Chronic Pain	17.6% 3/17 • Number of events 3 • Up to 2 years
Ear and labyrinth disorders Conductive Hearing Loss	5.9% 1/17 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Constipation	11.8% 2/17 • Number of events 2 • Up to 2 years
Infections and infestations Cytomegalovirus (CMV) viremia	11.8% 2/17 • Number of events 2 • Up to 2 years
Psychiatric disorders Depression	5.9% 1/17 • Number of events 1 • Up to 2 years
Investigations Electrolyte Abnormality	5.9% 1/17 • Number of events 1 • Up to 2 years
Psychiatric disorders Emotional disturbance	5.9% 1/17 • Number of events 1 • Up to 2 years
Nervous system disorders Epileptic seizures	5.9% 1/17 • Number of events 1 • Up to 2 years
General disorders Fever	23.5% 4/17 • Number of events 4 • Up to 2 years
Reproductive system and breast disorders Foreskin adhesions	5.9% 1/17 • Number of events 1 • Up to 2 years
Injury, poisoning and procedural complications Fracture	5.9% 1/17 • Number of events 1 • Up to 2 years
Hepatobiliary disorders Cholecystitis	5.9% 1/17 • Number of events 1 • Up to 2 years
Nervous system disorders Headaches	5.9% 1/17 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Hemorrhoids	5.9% 1/17 • Number of events 1 • Up to 2 years
Infections and infestations Human Herpesvirus 6 (HHV-6) viremia	5.9% 1/17 • Number of events 1 • Up to 2 years
Infections and infestations Human Metapneumovirus (hMPV)	5.9% 1/17 • Number of events 1 • Up to 2 years
Vascular disorders Hypertension	5.9% 1/17 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Hypomagnesemia	5.9% 1/17 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Iron overload	23.5% 4/17 • Number of events 4 • Up to 2 years
Metabolism and nutrition disorders Malnutrition	5.9% 1/17 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Nausea	17.6% 3/17 • Number of events 3 • Up to 2 years
Vascular disorders Neuropathy	5.9% 1/17 • Number of events 1 • Up to 2 years
Blood and lymphatic system disorders Neutropenia	5.9% 1/17 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders Osteopenia	5.9% 1/17 • Number of events 1 • Up to 2 years
Blood and lymphatic system disorders Pancytopenia	11.8% 2/17 • Number of events 2 • Up to 2 years
Investigations Post Transplant Immunodeficiency	100.0% 17/17 • Number of events 17 • Up to 2 years
Nervous system disorders Pseudoseizures	5.9% 1/17 • Number of events 1 • Up to 2 years
Infections and infestations Pulmonary aspergillosis	5.9% 1/17 • Number of events 1 • Up to 2 years
Skin and subcutaneous tissue disorders Rash	5.9% 1/17 • Number of events 1 • Up to 2 years
Blood and lymphatic system disorders Thrombocytopenia	5.9% 1/17 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Vomiting	17.6% 3/17 • Number of events 3 • Up to 2 years
Investigations Weight Loss	11.8% 2/17 • Number of events 2 • Up to 2 years
Investigations Abnormal alanine aminotransferase (ALT) and aspartate aminotransferase (AST)	5.9% 1/17 • Number of events 1 • Up to 2 years

Additional Information

Dr. Christopher Dvorak, MD

University of California, San Francisco

Phone: (415) 476-0554

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place