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

  • STATUS
    Recruiting
  • End date
    Jan 1, 2022
  • participants needed
    39
  • sponsor
    Case Comprehensive Cancer Center
Updated on 1 July 2021
cancer
remission
chronic myeloid leukemia
myeloid leukemia
lymphoid leukemia
fludarabine
hematologic malignancy
blast crisis
chronic lymphocytic leukemia
lymphoma
myelodysplastic syndromes
hodgkin's disease
myelodysplasia
flow cytometry
melphalan
thiotepa
intrathecal chemotherapy
blast cells

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.

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.

Details
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

Eligibility

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
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
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
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