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

  • End date
    Jan 1, 2022
  • participants needed
  • sponsor
    Case Comprehensive Cancer Center
Updated on 1 July 2021
chronic myeloid leukemia
myeloid leukemia
lymphoid leukemia
hematologic malignancy
blast crisis
chronic lymphocytic leukemia
myelodysplastic syndromes
hodgkin's disease
flow cytometry
intrathecal chemotherapy
blast cells


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.

Condition leukemia, Leukemia (Pediatric), leukemias
Treatment melphalan, Fludarabine, thiotepa, Keratinocyte Growth Factor (KGF)
Clinical Study IdentifierNCT03342196
SponsorCase Comprehensive Cancer Center
Last Modified on1 July 2021


Yes No Not Sure

Inclusion Criteria

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)
Chronic Myelogenous Leukemia (CML) in second chronic phase after accelerated or blast crisis
Myelofibrosis (MF)
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%
Relapsed or Refractory Lymphoid Malignancies (including non-Hodgkin Lymphoma, Hodgkin Lymphoma and Chronic Lymphocytic Leukemia) meeting the following
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
Eastern Cooperative Oncology Group (ECOG) Performance status 2
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

Exclusion Criteria

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%
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
Karnofsky Performance Statue (KPS) < 80
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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note