A Phase 2 interventional study of Melphalan and Thiotepa in Leukemia, sponsored by Case Comprehensive Cancer Center. Completed at 1 site in United States. Open to participants aged 1 Year to 65 Years. Per ClinicalTrials.gov, last updated 2025-12-03.
Sponsored by Case Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
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.
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.
2,381 studies on the registry are indexed under Leukemia; 253 are open to participants now.
This study's enrollment of 40 is close to the median of 40 across 1,769 interventional studies indexed under Leukemia.
Browse Leukemia studies →Case Comprehensive Cancer Center is the lead sponsor of 494 studies on the registry; 61 are open to participants now.
Of its 75 completed or terminated interventional studies of FDA-regulated products, 46 (61%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients with the following hematologic :
Acute myelogenous leukemia (AML): High-risk AML including:
Acute lymphoblastic leukemia (ALL)
High-risk CR1 including:
Myelofibrosis (MF):
Lymphoid Malignancies (including non-Hodgkin Lymphoma, Hodgkin Lymphoma and Chronic Lymphocytic Leukemia) meeting the following criteria:
Patient with either one or both:
Exclusion Criteria:
Patients with inadequate Organ Function as defined by:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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 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
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
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.
Time frame: Up to 1 year after transplant
Percentage of Patients With Leukemia Free Survival
Time frame: Up to 1 year after transplant
Average Overall Survival
Overall Survival (OS) at 1 year is the percentage of patients alive at 1 year after transplant.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 1 year after transplant
| Milestone | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Started | 40 |
| Completed | 39 |
| Not completed | 1 |
| Withdrew: Physician decision | 1 |
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 paticipants | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Percentage of Patients With Disease Free Survival | 65.8 |
| percentage of paticipants | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Percentage of Patients With Leukemia Free Survival | 65.5 |
Overall Survival (OS) at 1 year is the percentage of patients alive at 1 year after transplant.
| percentage of participants | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Average Overall Survival | 73.7 |
Relapse incidence at 1 year is the percentage of patients who experience relapse of their hematologic malignancy up to 1 year after transplant.
| percentage of participants | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Relapse Incidence | 13.16 |
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.
| percentage of paticipants | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Treatment Related Mortality | 21.05 |
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.
| percentage of participants | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Incidence of Acute GVHD | 76.31 |
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.
| percentage of participants | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Incidence of Chronic GVHD | 21.05 |
Neutrophil engraftment will be calculated as the days from transplant where the absolute neutrophil count (ANC) reaches \>500cells/ul x 3 days.
| Days | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Rate of Neutrophil Engraftment | 20.6 ± 5.69 |
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.
| Days | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Rate of Platelet Engraftment | 42.32 ± 31.4 |
Collected over Participants were followed for this study for 1 year following the allogeneic transplant, relapse, or death, whichever occured first.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Thiotepa + Fludarabine + Melphalan | 14/40 (35%) | 18/40 (45%) | 35/40 (87.5%) |
| Event | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Mucositis oralGastrointestinal disorders | 4/40 |
| NauseaGastrointestinal disorders | 3/40 |
| AnorexiaMetabolism and nutrition disorders | 2/40 |
| Febrile neutropeniaBlood and lymphatic system disorders | 2/40 |
| SyncopeNervous system disorders | 2/40 |
| Acute kidney injuryRenal and urinary disorders | 1/40 |
| Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders | 1/40 |
| Blood bilirubin increasedInvestigations | 1/40 |
| ConfusionPsychiatric disorders | 1/40 |
| DiarrheaGastrointestinal disorders | 1/40 |
| Event | Thiotepa + Fludarabine + Melphalan |
|---|---|
| NauseaGastrointestinal disorders | 11/40 |
| DiarrheaGastrointestinal disorders | 10/40 |
| FeverGeneral disorders | 10/40 |
| HypertensionVascular disorders | 10/40 |
| AnorexiaMetabolism and nutrition disorders | 8/40 |
| Abdominal painGastrointestinal disorders | 6/40 |
| Acute kidney injuryRenal and urinary disorders | 6/40 |
| FatigueGeneral disorders | 6/40 |
| VomitingGastrointestinal disorders | 6/40 |
| Mucositis oralGastrointestinal disorders | 5/40 |
| Age, Customized(Participants) | Thiotepa + Fludarabine + Melphalan |
|---|---|
| 10-19 | 1 |
| 20-29 | 4 |
| 30-39 | 7 |
| 40-49 | 3 |
| 50-59 | 12 |
| 60-69 | 12 |
| 70-79 | 1 |
| Sex: Female, Male(Participants) | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Female | 11 |
| Male | 29 |
| Ethnicity (NIH/OMB)(Participants) | Thiotepa + Fludarabine + Melphalan |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 40 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Thiotepa + Fludarabine + Melphalan |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 8 |
| White | 32 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Mar 2018 to primary completion in Jun 2024, 74 months.
Results were first posted in Dec 2025, 1 year 5 months after primary completion.
Of 144 non-industry phase 2 interventional studies under Leukemia, half reached primary completion within 92 months of starting (the median), counting those still running; a quarter within 60 and three quarters within 129. This study's 74 months is below that.
Counting every sponsor, half of 176 studies reached it within 76 months; a quarter within 44 and three quarters within 123.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Melphalan · Thiotepa · Fludarabine
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