Long-Term Follow-up: Phase I/II Clinical Study to Evaluate the Safety and Efficacy of the Infusion of RP-L102

Condition(s) studied

Investigational drug(s) / intervention(s)

RP-L102: CD34+ enriched cells from subjects with Fanconi anemia subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the FANCA gene, PGK-FANCA-WPRE

Study summary

Long-Term Follow-up: Phase I/II clinical study to evaluate the safety and efficacy of the infusion of RP-L102

Eligibility

Primary outcome measure(s)

• Survival in patients treated in the RP-L102 parent studies (RP-L102-0418, RP-L102-0319, RP-L102-0118). — From infusion in parent study to 15-years post-infusion.
  Overall survival and allogeneic-HSCT-free survival will be summarized using Kaplan-Meier estimates. Events for allogeneic-HSCT-free survival are allogeneic-HSCT or death. In addition, event-free survival based on death and any of the following events will be summarized similarly: (1) BMF, (2) MDS/AML, and (3) BMF and MDS/AML.
• Long term safety — From infusion in parent study to 15-years post-infusion.
  To evaluate long-term safety following infusion of hematopoietic cells transduced with the therapeutic lentiviral vector (LV).
• Long-term persistence of the therapeutic LV (provirus) in hematopoietic cells in the bone marrow (BM) and blood. — From infusion in parent study to 15-years post-infusion.
  To determine long-term persistence of the therapeutic LV (provirus) in hematopoietic cells in the bone marrow (BM) and blood, and to evaluate potential correlations between provirus/transgene persistence and hematologic stability (absence of bone marrow failure \[BMF\] or hematologic malignancy).
• Long-term clonality patterns. — From infusion in parent study to 15-years post-infusion.
  To determine long-term clonality patterns beyond the 3-year follow-up stipulated in the RP-L102 parent studies (RP-L102-0418, RP-L102-0319, RP-L102-0118).
• Replication-competent lentivirus (RCL) in serum and peripheral blood cells. — From infusion in parent study to 15-years post-infusion.
  To evaluate, when relevant, replication-competent lentivirus (RCL) in serum and peripheral blood cells (this will not be considered relevant for subjects in whom no evidence of RCL was identified during the initial year following investigational autologous cell infusion).
• Long-term stability and normalization of blood counts. — From infusion in parent study to 15-years post-infusion.
  To determine the long-term stability and normalization of blood counts in patients after RP-L102 infusion on the parent studies.
• Phenotypic correction of BM and peripheral blood cells — From infusion in parent study to 15-years post-infusion.
  To determine the phenotypic correction of BM and peripheral blood (PB) cells (as evaluated by resistance to DNA-damaging agents) in long-term follow-up after gene therapy. BM CFU MMC resistance will be summarized by percentage of patients with expression of ≥20% from at each timepoint
• Incidence of hematologic malignancies and solid organ tumors. — From infusion in parent study to 15-years post-infusion.
  To enable preliminary assessment of the incidence of hematologic malignancies (including acute myeloid leukemia \[AML\]/myelodysplastic syndrome \[MDS\]) and solid organ tumors (including squamous cell carcinoma of the head and neck); occurrence of these events will be evaluated in the context of the underlying rates of these malignancies in Fanconi anemia (FA) patient populations (both those who have not undergone allogeneic stem cell transplant and FA patients post-hematopoietic stem cell transplantation \[HSCT\]).

Trial sites (3)

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