Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT02579967
• Date of registration: 16/10/2015
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
• Scientific title: Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
• Date of first enrolment: November 19, 2015
• Target sample size: 254
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02579967
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Dimana Dimitrova, M.D.

• Name: Dimana Dimitrova, M.D.
• Affiliation: National Cancer Institute (NCI)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA - RECIPIENT:

- Patients age greater than or equal to 4 through 75 years

- PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two
criteria below:

1. PID as defined by identified genetic defect or, in the absence of a
PID-associated genetic mutation, patients with an immune defect potentially
amenable to allo BMT who meet the clinical history criteria below may be eligible
upon discussion with the PI

- Mutations should be confirmed in a CLIA-certified laboratory, if such
testing is available.

- Patients without a mutation must be deemed eligible and appropriate for allo
BMT by the PI. Some patients may meet the clinical history criteria listed
below, but will not be eligible if it is thought that their clinical history
is due to a condition apart from an immune defect. In addition, patients
with a PID of mild severity, such as those with selective IgA deficiency,
may meet at least two of the clinical history criteria, but may be deemed
inappropriate for allo BMT by the PI if it is felt that the risks of the
procedure outweigh the severity of the disease.

2. Clinical history of at least two of the following:

- Life-threatening, organ-threatening, or severely disfiguring infection

- Protracted or recurrent infections requiring unusually long or repeated
courses of antibiotics

- Infection with an opportunistic organism

- Chronic elevation in the blood (greater than or equal to 2 documented
elevations over a period of 6 months or longer) of a latent virus (EBV, CMV,
HHV6, HHV8, etc.)

- Evidence of immune dysregulation, as manifested by autoimmune disease,
atopy, hemophagocytic lymphohistiocytosis/macrophage activation syndrome,
granulomas, splenomegaly, or lymphadenopathy

- Patients with hemophagocytic lymphohistiocytosis or macrophage activation
syndrome related to an underlying lymphoma with no other clinical history
suggestive of a primary immunodeficiency will not be eligible

- Hypogammaglobulinemia, dysglobulinemia, or impaired response to vaccination

- Hematologic malignancy or lymphoproliferative disorder

- Tissue diagnosis should be confirmed by NCI Department of Pathology, if
prior biopsies are available

- Virus-associated solid tumor malignancy or pre-cancerous lesion

- Tissue diagnosis should be confirmed by NCI Department of Pathology, if
prior biopsies are available

- Availability of at least one 7-8/8 (9-10/10) HLA-matched related (excluding an
identical twin) or unrelated donor, or an HLA-haploidentical related donor

- Consensus among the PI, key AIs, and consultants (as necessary) that correction of the
patient s immune system through BMT has the potential to improve the patient s health,
quality of life, and/or life expectancy, after taking into consideration the patient s
existing non-hematopoietic, potentially irreversible organ dysfunction

- Adequate end-organ function, as measured by:

- Left ventricular ejection fraction (LVEF) greater than or equal to 40% by 2D
echocardiogram (ECHO) or MUGA, or left ventricular shortening fraction greater
than or equal to 20% by ECHO for patients receiving RIC or RIC-MMF, or RIC-SHORT,
or LVEF greater than or equal to 30% if the patient has radiologic evidence of
aortic, renal, or coronary artery vasculitis.

- Pulmonary function tests: DL(co) (corrected for hemoglobin) and FEV(1) greater
than or equal to 40% of predicted for the RIC, RIC-MMF, and RIC-SHORT arms; or in
pediatric patients, if unable to perform pulmonary function tests, there should
be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and
oxygen saturation >92% on room air. Calculations will be based on the values
reported in CRIS.

- Bilirubin <= 3.0 mg/dL (unless due to Gilbert s syndrome or hemolysis) for
patients receiving RIC, RIC-MMF, RIC-SHORT; ALT and AST 10 x ULN for patients
receiving RIC, RIC-MMF, RIC-SHORT. Patients who are above these bilirubin, ALT,
or AST thresholds may be eligible for the RIC, RIC-MMF, or RIC-SHORT arms if
evaluated by a hepatologist who deems the liver function test abnormalities to be
potentially reversible with bone marrow transplant.

- Estimated creatinine clearance of greater than or equal to 40 mL/min/1.73 m(2),
calculated using the Cockcroft-Gault equation for adults and Schwartz formula for
pediatric patients, for patients with creatinine levels above the institutional
upper limit of normal

- Karnofsky or Lansky performance status of greater than or equal to 60% or ECOG
performance status of 2 or less

- Ability of subject or Legally Authorized Representative (LAR) to understand and the
willingness to sign a written informed consent document

- Not pregnant or breastfeeding. As therapeutic agents used in this trial may be harmful
to a fetus, women of childbearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for at least one year post-allo BMT. Should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in the study, she
should inform her treating physician immediately.

- Disease status: Patients with malignancy are to be referred in remission for
evaluation, except in cases of virus-associated malignancy who may be referred at any
time. Should a patient have progressive disease or a donor becomes unavailable after
enrollment, the patient will be referred back to his/her primary
hematologist-oncologist for treatment. If this course of action is not in the best
interest of the patient according to the clinical judgment of the PI, then the patient
may receive standard treatment for the malignant disease under the current study,
although this should only occur as a bridge to transplant. If under either of these
settings, it becomes apparent that the patient will not be able to proceed to
transplant, then he/she must come off the study. Patients receiving standard therapy
will be told about the therapy, associated risks, potential


Age minimum: 4 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Common Variable Immunodeficiency

Immune System Diseases

Autoimmune Lymphoproliferative

Lymphoproliferative Disorders

Primary T-cell Immunodeficiency Disorders

Intervention(s)

Drug: Immunosuppression Only Conditioning -Closed with amendment L

Procedure: Allo BMT

Drug: Myeloablative Conditioning-Closed with amendment L

Drug: GVHD Prophylaxis

Drug: Reduced Intensity Conditioning

Primary Outcome(s)

For the RIC : To estimate the aGVHD-free, graft failure-free survival [Time Frame: +180 after allo BMT]

For the RIC-SHORT arm: To estimate the aGVHD-free, graft failure-free survival [Time Frame: +180 after allo BMT]

For the RIC-MMF arm: To determine the shortest duration of MMF that can be safely administered without excessive rates of graft failure or acute grade 3-4 GVHD [Time Frame: Duration de-escalation design]

Secondary Outcome(s)

Incidence of Chronic Graft-versus-host disease [Time Frame: 1 and 2 years post transplant]

Disease free survival [Time Frame: 1 year post-transplant]

Overall survival [Time Frame: 1 year post transplant]

Kinetics and durability of engraftment [Time Frame: days +28, +42, +60, +100, +180, and 1 year after allo BMT]

Transplant-related mortality [Time Frame: +180 and 1 year post transplant]

Kinetics and durability of lineage-specific donor chimerism [Time Frame: days +28 and +42]

Secondary graft failure [Time Frame: 1 year post transplant]

Event-free survival [Time Frame: 1 year post transplant]

Incidence of Acute Graft-versus-host disease [Time Frame: 1 year post transplant]

Secondary ID(s)

16-C-0003

160003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors