LeukemiaPhase 2NCT03342196
Thiotepa Plus Fludarabine+ Melphalan as the Preparative Regime for Alternative Donor Transplantation
A Phase 2 study testing Melphalan, Thiotepa and Fludarabine in people with Leukemia, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 65 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Melphalan, Thiotepa and Fludarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2018to 12 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
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- 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)
- Mixed Phenotypic Leukemia / Biphenotypic Leukemiain CR
- Chronic Myelogenous Leukemia (CML) in second chronic phase after accelerated or blast crisis.
- Myelofibrosis (MF):
- Intermediate-1, Intermediate-2 or high risk by Dynamic International Prognostic Scoring System (DIPSS-plus) or
- Monosomal karyotype or
- Presence of inv(3)/i(17q) abnormalities or
- Other unfavorable karyotype OR leukocytes ≥40 × 10(9) /L and
- Circulating blasts ≤ 9%
- Chronic Myelomonocytic Leukemia
- Relapsed or Refractory Lymphoid Malignancies (including non-Hodgkin Lymphoma, Hodgkin Lymphoma and Chronic Lymphocytic Leukemia) meeting the following criteria:
- Disease status: Stable Disease, Partial Remission or 2nd and 3rd Complete Remission. OR
- Have relapsed after autologous transplant or who have failed to collect for an autologous transplant.
- Age > 1 years, < 65yrs
- KPS Performance status ≥80
- Patients without a matched related or unrelated donor
- Patient with either one or both:
- Two 5/8 human leukocyte antigen (HLA) high resolution matched umbilical cord blood (UCB) grafts with a cell dose of 2.0x10^7 total number of nucleated cells per kilogram (TNC/kg) each, or
- A related haplo-identical donor
- Concurrent Therapy for Extramedullary Leukemia or central nervous system (CNS) Lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement. Maintenance therapy after transplant is allowed.
- Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
About this study
Official title: A Phase II Study of Thiotepa Added to Fludarabine and Melphalan as the Preparative Regime for Alternative Donor Transplantation
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.
Read the 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
- Being tested
- Melphalan, Thiotepa, Fludarabine
- Keywords
- Thiotepa, Fludarabine, Melphalan
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelphalanDrug
Also called Alkeran, Evomela
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.
ThiotepaDrug
Also called Tepadina
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.
FludarabineDrug
Also called Fludara
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Melphalan; Drug: Thiotepa; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 1 year after transplant
Percentage of Patients With Leukemia Free Survival
Measured: Up to 1 year after transplant
Secondary outcomes (7)
Average Overall Survival
Overall Survival (OS) at 1 year is the percentage of patients alive at 1 year after transplant.
Measured: Up to 1 year after transplant
Relapse Incidence
Relapse incidence at 1 year is the percentage of patients who experience relapse of their hematologic malignancy up to 1 year after transplant.
Measured: Up to 1 year after transplant
Treatment Related Mortality
Treatment Related Mortality (TRM) at 1 year is the percentage of patients who expire from treatment related toxicity attributed to transplant up to 1 year after transplant.
Measured: Up to 1 year after transplant
Incidence of Acute GVHD
Acute graft versus host disease (aGVHD) 1 year cumulative incidence is the percentage of patients who experience any aGVHD up to 1 year after transplant.
Measured: Up to 1 year after transplant
Incidence of Chronic GVHD
Chronic graft versus host disease (cGVHD) 1-year cumulative incidence is the percentage of patients who experience any cGVHD up to 1 year after transplant.
Measured: Up to 1 year after transplant
Rate of Neutrophil Engraftment
Neutrophil engraftment will be calculated as the days from transplant where the absolute neutrophil count (ANC) reaches >500cells/ul x 3 days.
Measured: Up to 1 year after transplant
Rate of Platelet Engraftment
Platelet engraftment will be calculated as the days from transplant where the platelet count reaches 20,000 platelets /ul without the need of transfusion of platelets for 7 days.
Measured: Up to 1 year after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2017
- Study start21 Mar 2018
- Primary completion12 Jun 2024
- Study completion12 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Leland Metheny, MD, Principal investigator, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03342196
- Sponsor's protocol ID
- CASE10Z17
- Status last verified
- Jun 2025
- First submitted
- 10 Nov 2017
- Last updated
- 3 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Thiotepa Added to Fludarabine and Melphalan as the Preparative Regime for Alternative Donor Transplantation
- ClinicalTrials.gov ID
- NCT03342196
- Acronym / sponsor ID
- CASE10Z17
- Conditions
- Leukemia
- Keywords
- Thiotepa, Fludarabine, Melphalan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 21 Mar 2018 (actual)
- Primary completion
- 12 Jun 2024 (actual)
- Study completion
- 12 Jun 2024 (actual)
- First posted
- 14 Nov 2017 (actual)
- Results
- Posted 3 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Thiotepa + Fludarabine + Melphalan | Experimental | Drug: Melphalan, Drug: Thiotepa, Drug: FludarabineMelphalan 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. |
Who may qualify
- Ages
- 1 year to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (35 listed)
- Patients with the following hematologic malignancies:
- Age > 1 years, < 65yrs
- KPS Performance status ≥80
- Patients without a matched related or unrelated donor
- Patient with either one or both:
Key exclusion criteria (13 listed)
- Patients with inadequate Organ Function as defined by:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelphalanAlso: Alkeran, EvomelaAlkylating 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 + Fludarabine + Melphalan |
| ThiotepaAlso: TepadinaThiotepa 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 | Thiotepa + Fludarabine + Melphalan |
| FludarabineAlso: FludaraFludarabine 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. | Drug | Thiotepa + Fludarabine + Melphalan |
Primary outcome
Percentage of Patients With Disease Free Survival
Time frame: Up to 1 year after transplant
Leukemia Free Survival (LFS) at 1 year is the percentage of patients alive and without evidence of hematologic malignancy at 1 year after transplant.
Percentage of Patients With Leukemia Free Survival
Time frame: Up to 1 year after transplant
7 secondary outcomes
Average Overall Survival
Time frame: Up to 1 year after transplant
Relapse Incidence
Time frame: Up to 1 year after transplant
Treatment Related Mortality
Time frame: Up to 1 year after transplant
Incidence of Acute GVHD
Time frame: Up to 1 year after transplant
Incidence of Chronic GVHD
Time frame: Up to 1 year after transplant
Rate of Neutrophil Engraftment
Time frame: Up to 1 year after transplant
Rate of Platelet Engraftment
Time frame: Up to 1 year after transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leland Metheny, MD principal investigator
Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melphalan, Thiotepa and Fludarabine in people with Leukemia, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Disease Free Survival (time frame: Up to 1 year after transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025.