histiocytosis (HLH) with refractory, recurrent orprogressive disease or intolerance with conventional HLH therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
The recommended starting dose of GAMIFANT is 1 mg/kg given as an intravenous infusionover 1 hour twice per week (every three to four days). Doses subsequent to the initial dose maybe increased based on clinical and laboratory criteria [see Dosage and Administration (2.4)].
Administer GAMIFANT until hematopoietic stem cell transplantation (HSCT) is performed orunacceptable toxicity. Discontinue GAMIFANT when a patient no longer requires therapy forthe treatment of HLH.
2.2 Monitoring to Assess Safety
Before Initiating GAMIFANT Treatment
Conduct testing for latent tuberculosis infections using the purified protein derivative (PPD) orIFNγ release assay and eva luate patients for tuberculosis risk factors prior to initiatingGAMIFANT. Administer tuberculosis prophylaxis to patients at risk for tuberculosis, or knownto have a positive PPD test result, or positive IFNγ release assay.
During GAMIFANT Treatment
Monitor for tuberculosis, adenovirus, EBV and CMV every 2 weeks and as clinically indicated.
2.3 Pre-Medications and Concomitant Medication Information
Pre-Medications
Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and for fungal infections priorto GAMIFANT administration.
Concomitant Medications
For patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at adaily dose of at least 5 to 10 mg/m2the day before GAMIFANT treatment begins. For patientswho were receiving baseline dexamethasone, they may continue their regular dose provided thedose is at least 5 mg/m2
. Dexamethasone can be tapered according to the judgment of the treatingphysician [see Clinical Studies (14)].
2.4 Dose Modification Based on Response
The GAMIFANT dose may be titrated up if disease response is unsatisfactory (see Table 1) [seeClinical Pharmacology (12.3)]. After the patient’s clinical condition is stabilized, decrease thedose to the previous level to maintain clinical response.
Table 1: Dose Titration Criteria
Treatment
Day
GAMIFANT Dose Criteria for Dose IncreaseDay 1 Starting Dose of 1
mg/kg
N/A
On Day 3 Increase to 3 mg/kg Unsatisfactory improvement in clinical condition, as
assessed by a healthcare provider AND at least one
of the following:
Fever – persistence or recurrence
Platelet count
If baseline < 50,000/mm3
and no
improvement to >50,000/mm3
If baseline > 50,000/mm3
and less than 30%
improvement
If baseline > 100,000/mm3 any decrease to <
100,000/mm3
Neutrophil count
If baseline < 500/mm3
and no improvement to
> 500/mm3
If baseline > 500 -1000/mm3
and decrease to
< 500/mm3
If baseline 1000-1500/mm3
and decrease to <
1000/ mm3
Ferritin (ng/mL)
If baseline ≥ 3000 ng/mL and < 20% decrease
If baseline < 3000 ng/mL and any increase to >
3000 ng/mL
Splenomegaly – any worsening
Coagulopathy (both D-Dimer and Fibrinogen
must apply)
D-Dimer
Treatment
Day
GAMIFANT Dose Criteria for Dose Increase
If abnormal at baseline and no
improvement
Fibrinogen (mg/dL)
If baseline levels ≤ 100 mg/dL and no
improvement
If baseline levels > 100 mg/dL) and any
decrease to |
