IRB Study Number 20-932
Status Recruiting
Institutes Taussig Cancer Institute, Pediatric Institute
Description
Primary Objective
To compare the time to resolution of macroscopic hematuria in recipients of Viralym-M (also known as ALVR-105) to that in patients receiving placebo.
Secondary Objectives
To compare the time to resolution of bladder pain as measured by Clinical Outcome Assessments (coas) in recipients of Viralym-M to that in patients receiving placebo.
To assess number of days in the hospital (for any reason including, but not limited to, hemorrhagic cystitis [HC]) over the 24-week study period
To assess the incidence and severity of acute graft versus host disease (GVHD) and cytokine release syndrome (CRS) over the 24-week study period
To assess time to resolution of viremia for all target viruses over the 24-week study period (only for patients with detectable viremia at baseline)
To assess average daily bladder pain (11-point numeric rating scale [NRS]) over the 6-week period from randomization
Inclusion Criteria
Over 1 year of age at the time of informed consent/assent.
Had an allogeneic HCT performed at least 21 days and not more than 1 year prior to randomization.
Myeloid engraftment confirmed, defined as an absolute neutrophil count 500/mm3 for 3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm3 at the time of randomization.
Diagnosed with HC based on the following criteria (all 3 criteria must be met):
a. Clinical signs and symptoms of cystitis, including dysuria, lower abdominal pain, and/or other bladder-associated pain or spasms.
b. Grade 3 hematuria (per Bedi scale43 [see Section 6.1]).
c. Viruria of >5 log10 copies/mL of at least 1 target virus (ie, BKV, JCV, AdV, CMV, EBV, and/or HHV-6).
i. Randomization of patient may be based on viruria data obtained from either the local or central laboratory. Note: If the results from the local laboratory are used for determination of eligibility/inclusion, an additional pre-randomization sample for viruria testing must be collected for assay at the central laboratory. These results do not have to be available at the time of randomization or study treatment infusion.
ii. At baseline, all patients will have quantitative viruria performed by the central laboratory. Central laboratory results will be used for comparative purposes (change in viruria over time) as well as for inclusion in the modified Intent-to-Treat (mITT) Population (see Section 8.1.3).
At least 1 identified, suitably matched Viralym-M cell line for infusion is available. (If a Viralym-M line is not available, the following patient data will be collected: demographic data and HLA type).
Willing and able to provide written informed consent to participate in the study, or a parent or legal guardian is willing and able to provide written informed consent and the potential pediatric patient is able to provide assent in a manner approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and local regulations.
Agree to use an effective contraceptive method during the study and for a minimum of 90 days after study treatment for all patients of childbearing potential. Effective methods of contraception for use in this study are:
o Intrauterine device.
o Stable dose of hormonal birth control, such as those listed below, for at least 3 months prior to enrollment
Hormonal contraceptive tablets.
Injectable hormonal contraceptives.
Implanted hormonal contraceptives.
Cutaneous contraceptive patches.
Intravaginal hormonal contraceptive rings.
o At least 1 barrier method. Effective barrier methods for use in this study are:
Male or female condom.
Diaphragm.
Note: A female is considered to be of “childbearing potential” if she has experienced menarche and is not permanently sterile or postmenopausal (postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause and with a serum follicle-stimulating hormone test result in the postmenopausal range). Surgically sterile females (eg, status post-hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) may enter the study with historical documentation of the surgical procedure and a negative pregnancy test at study entry. If a female patient has a male partner who has had surgery to prevent pregnancy (vasectomy), that will be considered evidence of effective contraception for the purpose of this study, provided: a) that the male partner is the sole sexual partner of the patient, and b) historical documentation of the procedure is provided. Note: In addition to routine contraceptive methods, “effective contraception” also includes heterosexual celibacy for the entire duration of the study and for 90 days after the last dose of study treatment. If at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures specified above, he/she is responsible for initiating effective contraceptive measures as defined above.
- A negative serum pregnancy test for female patients of childbearing potential.
Exclusion Criteria
Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
Prior therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies within 28 days of randomization.
Evidence of active Grade >2 acute GVHD (for additional information on acute GVHD grading and severity, see Appendix E).
Presence of uncontrolled or progressive bacterial or fungal infections (ie, evidence of bacteremia, fungemia, dissemination, and/or organ-specific infection not well controlled by present therapies).
Presence of progressive, uncontrolled viral infections (ie, evidence of viremia, dissemination, and/or organ-specific infection not well controlled by present therapies) not targeted by Viralym-M.
Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
Known or presumed pneumonia secondary to any organism.
Donor lymphocyte infusion performed within 21 days prior to randomization.
Hemodynamic or respiratory instability defined as either of the following:
o Requirement for continuous infusions of inotropes or vasopressors for blood pressure support.
o Requirement for endotracheal intubation or mechanical ventilation.
Hemoglobin <7 g/dL despite RBC transfusions.
Evidence of active hepatic sinusoidal obstruction syndrome.
Liver dysfunction, defined as liver transaminases (ie, aspartate aminotransferase or alanine aminotransferase) >5 times the upper limit of normal (ULN) or direct bilirubin >2 times the ULN reference.
Renal dysfunction, defined as eGFR <30 mL/min/1.73 m2 (using creatinine clearance as calculated with the Cockcroft-Gault equation for adults and the Schwartz equation for pediatric patients).
Evidence of encephalopathy.
Relapse of primary malignancy.
Receipt of other investigational antiviral treatments (eg, brincidofovir) within 28 days prior to randomization and throughout the duration of the study.
Pregnant or lactating or planning to become pregnant.
