ImmunodeficiencyPhase 1/2NCT01027702

Donor Lymphocyte Infusion After Alternative Donor Transplantation

A Phase 1/2 study testing Infusion of donor lymphocytes in people with Immunodeficiency, run by Wake Forest University Health Sciences at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to determine the ability of a donor lymphocyte infusion (DLI) given with methotrexate to hasten immune recovery without causing severe graft-versus-host disease (GVHD) in recipients who have had a T-cell depleted transplant. Read more about this study

Who is it for?: Ages Up to 30 years
Conditions the study is for: Immunodeficiency
What is being tested?: Infusion of donor lymphocytes
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 38 participants
Where: 1 siteUnited States
Study dates: Aug 2009to Nov 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 30 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Patients must have been treated on the LCH BMT 09-01 protocol
Signed informed consent by patient or legal guardian

Who cannot join

Active GVHD at the time when DLI are due
History of acute GVHD > grade I prior to DLI
Disease due to viral infection (eg. CMV) when DLI are due (asymptomatic viral replication or viral shedding is not a contraindication)
Uncontrolled bacterial or fungal infection
O2 saturation by pulse oximetry < 95%
Bilirubin > 3mg/dL or ALT > 5 x upper limit of normal

Show all 11Show fewer

Creatinine > 3x baseline (at transplant)
ANC (WBC x % neutrophils + bands) < 500/ul
Significant effusions (eg. pleural or pericardial) or ascites
EBV-related PTLD
Persistent or increasing mixed chimerism requiring therapeutic DLI as defined on the LCH BMT 09-01 protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

Levine Children's Hospital, Carolinas Medical Center
Charlotte, North Carolina, 28203

Other trials in United States

About this study

Official title: Phase I/II Study of Donor Lymphocyte Infusion With Methotrexate GVHD Prophylaxis to Hasten Immune Reconstitution After CD34+ Cell-Selected Transplant

Read the detailed description

Studies have shown that giving donor T cells after a mismatched T cell-depleted stem cell transplant can speed up recovery of T cells in the patient. This approach can cause severe graft versus host disease (GVHD). The purpose of this study is to determine whether giving a donor lymphocyte infusion (DLI) with methotrexate can accelerate immune recovery in recipients of T cell-depleted stem cell transplants. Thirty days after a T-cell depleted transplant, patients will be given a DLI. They will be monitored for immune recovery as measured by CD4 count and for GVHD toxicity.

Patients will be separated into six cohorts based on dose of DLI received: 3 x 10^4, 4 x 10^4, 5 x 10^4, 6 X 10^4, 8 x 10^4, and 10 X10^4 cells/ kg of body weight. A minimum of 3 patients will be tested at each dose starting with the lowest dose. Dose escalation will continue until the dose associated with CD4 count >100 at Day +120 after transplant without significant GVHD is determined. All patients will receive thirteen doses of methotrexate after the DLI to prevent GVHD. Patients will be followed for 2 years for outcomes.

Conditions: Immunodeficiency
Being tested: Infusion of donor lymphocytes
Keywords: Donor Lymphocyte Infusion, Immune Recovery, T cell depleted transplant, Mismatched related donor transplants, Unrelated donor transplants
Medical subject headings: Immunologic Deficiency Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Infusion of donor lymphocytesBiological
A donor lymphocyte infusion will be given to provide T cells. There will be a dose escalation: 3 x 10^4, 4 x 10^4, 5 x 10^4, 6 X 10^4, 8 x 10^4, and 10 X10^4 cells/kg body weight. At least three patients will be assessed at each dose to determine safety before dose is increased.

Study groups in NCT01027702
Study group	Role	What they receive
Infusion of donor lymphocytes	Experimental	Patients will receive an infusion of donor lymphocyte after T-cell depleted transplant. Receives: Biological: Infusion of donor lymphocytes

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Immune Recovery Following Transplantation
Immune recovery was measured by CD4+ cells > 100/μL by Day 120 following transplantation
Measured: 120 days after transplant
Incidence and Severity of GVHD
Patients were evaluated for acute GVHD due to prophylactic DLI between the day of prophylactic DLI infusion and Day +180 after transplant. GVHD was graded using standard criteria.
Measured: 180 days after transplant

Secondary outcomes (1)

Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD)
Subjects were actively monitored for adenovirus, cytomegalovirus (CMV), human herpes virus 6 (HHV6), and Epstein-Barr virus (EBV) as part of standard post-transplant care. All infections were collected from date of DLI until 1 year after transplant.
Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2009Nov 2016

First posted9 Dec 2009 (estimated)
Study startAug 2009
Primary completionNov 2016
Study completionNov 2016

Why it stopped: Sponsor/ PI leaving institution, no plans to continue this research at this time

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for ImmunodeficiencyStudies of the same condition, open and under way.
More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01027702
Sponsor's protocol ID: LCH BMT 09-02
Status last verified: Oct 2017
First submitted: 7 Dec 2009
Last updated: 22 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Gilman AL, Leung W, Cowan MJ, Cannon M, Epstein S, Barnhart C, Shah K, Hyland M, Fukes T, Ivanova A. Donor lymphocyte infusion and methotrexate for immune recovery after T-cell depleted haploidentical transplantation. Am J Hematol. 2018 Feb;93(2):169-178. doi: 10.1002/ajh.24949. Epub 2017 Nov 17.
PubMed 29047161

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 22 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Study of Donor Lymphocyte Infusion With Methotrexate GVHD Prophylaxis to Hasten Immune Reconstitution After CD34+ Cell-Selected Transplant
ClinicalTrials.gov ID: NCT01027702
Acronym / sponsor ID: LCH BMT 09-02
Conditions: Immunodeficiency
Keywords: Donor Lymphocyte Infusion, Immune Recovery, T cell depleted transplant, Mismatched related donor transplants, Unrelated donor transplants
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sponsor/ PI leaving institution, no plans to continue this research at this time
Enrolment: 38 participants (actual)
Lead sponsor: Wake Forest University Health SciencesUniversity, hospital or other
Study start: Aug 2009
Primary completion: Nov 2016 (actual)
Study completion: Nov 2016 (actual)
First posted: 9 Dec 2009 (estimated)
Results: Posted 8 Nov 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Infusion of donor lymphocytes	Experimental	Biological: Infusion of donor lymphocytesPatients will receive an infusion of donor lymphocyte after T-cell depleted transplant.

Who may qualify

Ages: Up to 30 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (2 listed)

Patients must have been treated on the LCH BMT 09-01 protocol
Signed informed consent by patient or legal guardian

Key exclusion criteria (11 listed)

Active GVHD at the time when DLI are due
History of acute GVHD > grade I prior to DLI
Disease due to viral infection (eg. CMV) when DLI are due (asymptomatic viral replication or viral shedding is not a contraindication)
Uncontrolled bacterial or fungal infection
O2 saturation by pulse oximetry < 95%

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Infusion of donor lymphocytesA donor lymphocyte infusion will be given to provide T cells. There will be a dose escalation: 3 x 10^4, 4 x 10^4, 5 x 10^4, 6 X 10^4, 8 x 10^4, and 10 X10^4 cells/kg body weight. At least three patients will be assessed at each dose to determine safety before dose is increased.	Biological	Infusion of donor lymphocytes

Primary outcome

Number of Participants With Immune Recovery Following Transplantation
Time frame: 120 days after transplant
Immune recovery was measured by CD4+ cells > 100/μL by Day 120 following transplantation
Incidence and Severity of GVHD
Time frame: 180 days after transplant
Patients were evaluated for acute GVHD due to prophylactic DLI between the day of prophylactic DLI infusion and Day +180 after transplant. GVHD was graded using standard criteria.

1 secondary outcome

Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD)
Time frame: 1 year

Results and safety

Results posted to the registry on 8 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MMRD: 3 x 10^4/kg DLI + MTX to Day +24	4	3
MMRD: 3 x 10^4/kg DLI + MTX to Day +52	4	2
MMRD: 4 x 10^4/kg DLI + MTX to Day +52	3	2
MMRD: 4 x 10^4/kg DLI + MTX to Day +80	14	10
MMRD: 5 x 10^4/kg DLI + MTX to Day +80	10	9
MUD: 3 x 10^4/kg DLI + MTX to Day +24	1	1
MUD: 3 x 10^4/kg DLI + MTX to Day +52	2	1

Primary outcome: Number of Participants With Immune Recovery Following Transplantation

Time frame: 120 days after transplant. Count of participants. Unit: Participants

Measure	MMRD: 3 x 10^4/kg DLI + MTX to Day +24 n = 3	MMRD: 3 x 10^4/kg DLI + MTX to Day +52 n = 2	MMRD: 4 x 10^4/kg DLI + MTX to Day +52 n = 2	MMRD: 4 x 10^4/kg DLI + MTX to Day +80 n = 10	MMRD: 5 x 10^4/kg DLI + MTX to Day +80 n = 9	MUD: 3 x 10^4/kg DLI + MTX to Day +24 n = 1	MUD: 3 x 10^4/kg DLI + MTX to Day +52 n = 1
Value	1	1	1	4	6	1	1

Population analysed: Patients who received subsequent therapy, such as therapeutic DLI (eg. for treatment of viral infection or relapse), chemotherapy, or a PBSC infusion were considered not evaluable as this could interfere with response assessments.

Primary outcome: Incidence and Severity of GVHD

Time frame: 180 days after transplant. Count of participants. Unit: Participants

Measure	MMRD: 3 x 10^4/kg DLI + MTX to Day +24 n = 3	MMRD: 3 x 10^4/kg DLI + MTX to Day +52 n = 2	MMRD: 4 x 10^4/kg DLI + MTX to Day +52 n = 2	MMRD: 4 x 10^4/kg DLI + MTX to Day +80 n = 10	MMRD: 5 x 10^4/kg DLI + MTX to Day +80 n = 9	MUD: 3 x 10^4/kg DLI + MTX to Day +24 n = 1	MUD: 3 x 10^4/kg DLI + MTX to Day +52 n = 1
No GVHD/ Grade I GVHD	2	1	1	9	8	1	1
Grade II GVHD	0	1	1	1	1	0	0
Grade III/IV GVHD	1	0	0	0	0	0	0

Population analysed: Patients that had not had grade II-IV acute GVHD following prophylactic DLI but received therapeutic DLI (eg. for treatment of viral infection or relapse), chemotherapy, or a PBSC infusion prior to Day +180 were considered not evaluable because these therapies may cause or prevent GVHD and affect the determination of this endpoint.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From the time of donor lymphocyte infusion (DLI) up to one year after transplant.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Infusion of Donor Lymphocytes	32 of 38 (84.2%)	27 of 38 (71.1%)	12 of 38

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29047161Gilman AL, Leung W, Cowan MJ, Cannon M, Epstein S, Barnhart C, Shah K, Hyland M, Fukes T, Ivanova A. Donor lymphocyte infusion and methotrexate for immune recovery after T-cell depleted haploidentical transplantation. Am J Hematol. 2018 Feb;93(2):169-178. doi: 10.1002/ajh.24949. Epub 2017 Nov 17.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Andrew Gilman, MD principal investigator

Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Infusion of donor lymphocytes in people with Immunodeficiency, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Immune Recovery Following Transplantation (time frame: 120 days after transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01027702, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.