NCT03342196

Thiotepa Plus Fludarabine+ Melphalan as the Preparative Regime for Alternative Donor Transplantation

A Phase II Study of Thiotepa Added to Fludarabine and Melphalan as the Preparative Regime for Alternative Donor Transplantation

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 1 Year – 65 Years
• Healthy volunteers: Not accepted

Summary

In the United States, thiotepa has been utilized in reduced intensity conditioning regimens for alternative donor courses (double umbilical cord blood transplant (dUCBT) and haplo-identical transplants). The hypothesis is that thiotepa at a dose of 10mg/kg, in combination with melphalan (100mg/m2) and fludarabine (160mg/m2) as a reduced intensity conditioning regimen for alternative donor transplant is safe and effective in patients with hematologic malignancies. Given that this regimen has been investigated extensively, and the current study proposes to confirm those previous observations with a small modification (melphalan dose reduction due to previous mucositis rates with higher doses), this will be a phase II study designed to measure disease-free-survival.

Detailed description

Primary Objective: To assess the effectiveness of Thiotepa, Fludarabine, and Melphalan in alternative donor transplants as measured by leukemia free survival. Secondary Objective: To assess the 1- year OS, Relapse, TRM, aGVHD and cGVHD rates and the rates of neutrophil and platelet engraftment. Study Design This is a Phase II study of Thiotepa, Fludarabine, and Melphalan in alternative donor transplants. Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. Subjects will be followed for up to 1 year or until progression of disease, relapse, or death.

Conditions

• Leukemia

Interventions

Type	Name	Description
DRUG	Melphalan	Alkylating agent which is a derivative of mechlorethamine that inhibits DNA and RNA synthesis via formation of carbonium ions; cross-links strands of DNA; acts on both resting and rapidly dividing tumor cells. Melphalan may cause a lowering of the white blood cell or platelet counts, leading to an increased risk of infection and frequent bruising or bleeding. It may cause damage to the GI tract causing mouth sores, nausea, vomiting, and diarrhea. Other side effects may include loss of appetite, liver abnormalities, hair loss, swelling, fatigue, sleepiness, skin rash.
DRUG	Thiotepa	Thiotepa is an alkylating agent which produces cross-linking of DNA strands leading to inhibition of DNA, RNA, and protein synthesis; thiotepa is cell-cycle independent. Thiotepa may cause a lowering of the white blood cell or platelet counts, leading to an increased risk of infection and frequent bruising or bleeding. It may cause damage to the GI tract causing mouth sores, nausea, vomiting, and diarrhea. Other side effects may include loss of appetite, liver abnormalities, hair loss, swelling, fatigue, sleepiness, skin rash.
DRUG	Fludarabine	Fludarabine is an antineoplastic fluorinated nucleoside analog and inhibits DNA synthesis through inhibition of polymoerase alpha after incorporation into DNA. Fludarabine may cause a lowering of the white blood cell or platelet counts, leading to an increased risk of infection and frequent bruising or bleeding. Other side effects may include loss of appetite, liver abnormalities, hair loss, swelling, fatigue, sleepiness, skin rash, and lower limb weakness.

Timeline

• Start date: 2018-03-21
• Primary completion: 2024-06-12
• Completion: 2024-06-12
• First posted: 2017-11-14
• Last updated: 2025-12-03
• Results posted: 2025-12-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study