Thiotepa, Fludarabine Phosphate, and Melphalan Hydrochloride in Treating Patients with Blood Cancer Undergoing Donor Stem Cell Transplant

Status: Active


This phase II trial studies how well thiotepa, fludarabine phosphate, and melphalan hydrochloride work in treating patients with blood cancer who are undergoing a donor stem cell transplant. Drugs used in chemotherapy, such as thiotepa, fludarabine phosphate, and melphalan hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Eligibility Criteria

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) ** CR2 or 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 x 10(9)/L AND ** Circulating blasts =< 9% * Relapsed or refractory lymphoid malignancies (including non-Hodgkin lymphoma, Hodgkin lymphoma) meeting the following criteria: ** Disease status: Stable disease, partial remission or 2nd and 3rd complete remission ** 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 HLA or better high resolution matched umbilical cord blood (UCB) grafts with a cell dose of 2.0 x 10^7 total nucleated cell (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

  • Creatinine clearance < 30 ml/min
  • Bilirubin >= 2 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) >= 2 X institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 2 X institutional upper limit of normal
  • Pulmonary function: Carbon monoxide diffusing capability (DLCOc) < 40% normal
  • Cardiac: left ventricular ejection fraction < 35%
  • 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

Locations & Contacts


Case Comprehensive Cancer Center
Status: Active
Contact: Leland L. Metheny
Phone: 216-844-0139

Trial Objectives and Outline


I. To assess the effectiveness of thiotepa, fludarabine phosphate (fludarabine), and melphalan hydrochloride (melphalan) in alternative donor transplants as measured by leukemia free survival.


I. To assess the 1-year overall survival (OS), relapse, transplant mortality rate (TRM), acute graft versus host disease (aGVHD) and chronic graft versus host disease (cGVHD) rates and the rates of neutrophil and platelet engraftment.


Patients receive keratinocyte growth factor intravenously (IV) on days -11 to -9, melphalan hydrochloride IV over 30-60 minutes on day -8, thiotepa IV over 30-60 minutes on day -7, and fludarabine phosphate IV over 30-60 minutes on days -6 to -3. Patients undergoing double umbilical cord blood transplant (dUCBT) receive anti-thymocyte globulin (ATG) IV on days -3 to -2.

Patients undergo standard of care transplant on day 0 and receive keratinocyte growth factor IV on days on days 0-2. Patients undergoing haplo-identical transplant also receive cyclophosphamide IV on days 3-4.

After completion of study treatment, patients are followed up for 30 days, at 100 days, and at 6, 9, and 12 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Leland L. Metheny

Trial IDs

Primary ID CASE10Z17
Secondary IDs NCI-2018-01003 ID NCT03342196