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

NCT03342196 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE10Z17
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia

Keywords

Thiotepa; Fludarabine; Melphalan

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients With Disease Free Survival

  Leukemia Free Survival (LFS) at 1 year is the percentage of patients alive and without evidence of hematologic malignancy at 1 year after transplant.

  Up to 1 year after transplant

• Percentage of Patients With Leukemia Free Survival

  Up to 1 year after transplant

Secondary Outcomes (7)

• Average Overall Survival

  Up to 1 year after transplant

• Relapse Incidence

  Up to 1 year after transplant

• Treatment Related Mortality

  Up to 1 year after transplant

• Incidence of Acute GVHD

  Up to 1 year after transplant

• Incidence of Chronic GVHD

  Up to 1 year after transplant

Study Arms (1)

Thiotepa + Fludarabine + Melphalan

EXPERIMENTAL

Melphalan 100 mg/m2 on day -8 Thiotepa 10 mg/kg on day -7 Fludarabine 160 mg/m2 in divided doses given on days -6, -5, -4 and -3.

Drug: Melphalan; Drug: Thiotepa; Drug: Fludarabine

Interventions

Melphalan DRUG

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.

Also known as: Alkeran, Evomela

Thiotepa + Fludarabine + Melphalan

Thiotepa DRUG

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.

Also known as: Tepadina

Thiotepa + Fludarabine + Melphalan

Fludarabine DRUG

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.

Also known as: Fludara

Thiotepa + Fludarabine + Melphalan

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with the following hematologic malignancies:
• Acute myelogenous leukemia (AML): High-risk AML including:
• Antecedent hematological disease (e.g., myelodysplasia (MDS))
• Treatment-related leukemia
• Complete Remission (CR1) with poor-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, complex cytogenetics)
• Second complete remission (CR2) or third complete remission (CR3)
• Induction failure or 1st relapse with ≤ 10% blasts in the marrow
• Acute lymphoblastic leukemia (ALL)
• High-risk CR1 including:
• Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23 rearrangements)
• Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy
• No CR within 4 weeks of initial treatment
• Induction failure with ≤ 10% blasts in the marrow
• CR2 or CR3
• Myelodysplastic syndromes (MDS), Intermediate, High or Very High Risk by the revised international prognostic scoring system (IPSS-R)

You may not qualify if:

• Patients with inadequate Organ Function as defined by:
• Creatinine clearance \<50ml/min
• Bilirubin \> twice institutional upper limit of normal
• aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) ≥ three times institutional upper limit of normal
• Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≥ three times institutional upper limit of normal
• Pulmonary function: diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DLCOc) \< 60% normal
• Cardiac: left ventricular ejection fraction \< 50%
• Karnofsky Performance Statue (KPS) \< 80
• Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with Reduced Intensity Conditioning (RIC) have the significant potential for teratogenic or abortifacient effects.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
• Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds
• Presence of donor-specific antibodies against chosen graft source.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Leukemia

Interventions

Melphalan; Thiotepa; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Principle Investigator
• Organization: University Hospitals, Case Comprehensive Cancer Center

Leland.Metheny@uhhospitals.org

216-844-0139

Study Officials

• Leland Metheny, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2017
• First Posted: November 14, 2017
• Study Start: March 21, 2018
• Primary Completion: June 12, 2024
• Study Completion: June 12, 2024
• Last Updated: December 3, 2025
• Results First Posted: December 3, 2025

Record last verified: 2025-06

Locations

US (1)