Clinical trial NCT02210078: Donor Cytomegalovirus-Specific Cytotoxic T-Lymphocytes in Treating Patients With a Persistent Cytomegalovirus Infection
Official title: Most Closely HLA Matched Allogeneic CMV Specific Cytotoxic T-Lymphocytes (CTL) to Treat CMV Infection After Hemapoietic Stem Cell Transplantation (HSCT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cytomegaloviral Infection
Hematopoietic and Lymphoid Cell Neoplasm
Malignant Solid Neoplasm
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-08-06
Enrollment: 49
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well donor cytomegalovirus-specific cytotoxic T-lymphocytes work in treating patients with a cytomegalovirus infection that has come back or has not gotten better despite standard therapy. White blood cells from donors who have been exposed to cytomegalovirus may be effective in treating patients with a cytomegalovirus infection.

Detailed description: PRIMARY OBJECTIVE:

I. To assess the efficacy, feasibility and safety of administering most closely human leukocyte antigen (HLA)-matched cytomegalovirus (CMV) specific cytotoxic T-lymphocytes (HMC-CTLs) generated by "gamma-catch" to mediate antiviral activity in hematopoietic stem cell transplantation (HSCT) recipients with CMV infections.

SECONDARY OBJECTIVE:

I. To assess the persistency of the administered HMC-CTLs generated by "gamma-catch" and their contribution immune reconstitution.

OUTLINE:

Patients receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes intravenously (IV). Patients with partial response, stable disease, or progressive disease may receive an additional dose of allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes at a minimum of 2 weeks from the first infusion.

After completion of study treatment, patients are followed up periodically for 12 months.

Eligibility criteria: Inclusion criteria:

Patients with or without a malignancy; and/or any type of autologous or allogeneic HSCT; and/or patients who are immunocompromised with CMV infection will be included.

Persistent CMV infection despite optimum anti-viral therapy

1. Patients with CMV disease: defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates OR
2. Failure of antiviral therapy: defined as the continued presence of DNAemia (defined as \>/= 137 copies/ml by PCR) for at least 2 weeks of CMV antiviral therapy OR

   1. Optimum therapy is defined as at least 14 days of therapy with Ganciclovir, Foscarnet, Cidofovir, or Valganciclovir for patients with disease or CMV viremia.
   2. Relapse while on CMV antiviral therapy defined as recurrence of DNAemia while being on at least 2 weeks of antiviral therapy OR
3. Patients who cannot tolerate standard anti-viral therapy and cannot continue anti-viral treatment due to side effect profile will be eligible independent of anti-viral therapy duration.

Clinical status at enrollment to allow tapering of steroids equal to or less than 0.5 mg/kg/day of prednisone.

Patients with chronic GVHD if on prednisone equal to or less than 0.5 mg/kg and not receiving second-line GVHD treatments like Pentostatin, Infliximab, Etanercept, etc.

Written informed consent and/or signed assent line from patient, parent or guardian.

Written informed consent from patient or legally authorized representative (LAR). Patients with cognitive impairment are eligible.

* Negative pregnancy test in female patients of childbearing potential.
* Patients ≥ 2 years.
* English and non-English speaking patients are eligible.
* Patients enrolled on this study may be enrolled on other IND studies at the discretion of the PI.

Exclusion criteria:

* Patients receiving prednisone \>0.5 mg/kg/day at time of enrollment, or have received ATG, donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment.
* Patients with other uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. Patients with ongoing viral infections are excluded.
* Patients with active acute GVHD grades II-IV.

Primary outcomes:
measure: Success, defined as R1 and R2 without treatment failure
timeFrame: Up to 4 weeks after second CTL infusion
Secondary outcomes:
measure: Overall survival time
timeFrame: Up to 12 months
measure: Disease-free survival time
timeFrame: Up to 12 months
measure: Graft-versus-host disease
timeFrame: Up to 12 months
measure: Secondary graft failure
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Betul Oran
role: PRINCIPAL_INVESTIGATOR
References: