Clinical Trials /

Clofarabine Pre-allogeneic Stem Cell Transplant for Non-remission AML

NCT04002115

Description:

The Investigators would like to study the incidence of complete remission (CR) at day +30 after Clofarabine followed by haploidentical transplant. The conditioning regimen used is Fludarabine, Busulfan (2 doses) and Total Body Irradiation (TBI) with post transplant cyclophosphamide for patients with Acute Myeloid Leukemia (AML) who are not in remission prior to considering allogeneic transplant with haploidentical donors.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clofarabine Pre-allogeneic Stem Cell Transplant for Non-remission AML
  • Official Title: Clofarabine Followed by Hematopoietic Stem Cell Transplant Using Fludarabine, Busulfan, and Total-Body Irradiation With Post-Transplant Cyclophosphamide for Non-remission Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 18-011
  • NCT ID: NCT04002115

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
ClofarabineClolarClofarabine 30 mg/m^2
FludarabineFludaraClofarabine 30 mg/m^2
BusulfanBusulfexClofarabine 30 mg/m^2
CyclophosphamideCytoxanClofarabine 30 mg/m^2
Granulocyte Colony-Stimulating FactorFilgrastim G-CSFClofarabine 30 mg/m^2
TacrolimusPrografClofarabine 30 mg/m^2
CellceptMycophenolate Mofetil (MMF)Clofarabine 30 mg/m^2

Purpose

The Investigators would like to study the incidence of complete remission (CR) at day +30 after Clofarabine followed by haploidentical transplant. The conditioning regimen used is Fludarabine, Busulfan (2 doses) and Total Body Irradiation (TBI) with post transplant cyclophosphamide for patients with Acute Myeloid Leukemia (AML) who are not in remission prior to considering allogeneic transplant with haploidentical donors.

Detailed Description

      Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction
      failures. In these patients who do not achieve remission with two cycles of standard
      induction therapies, the probability of achieving remission with subsequent inductions is
      limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these
      patients, but high relapse rate and transplant-related mortality often preclude them to
      proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need
      in current HSCT practice, particularly if the patient does not have a Human Leukocyte Antigen
      (HLA)-matched donor identified by the time of two induction failures.

      Salvage chemotherapy with clofarabine appears to be another promising option in relapsed and
      refractory AML. Clofarabine is a second-generation purine nucleoside analog with substantial
      single-agent activity in adult patients with AML. It is an effective immunosuppressive agent
      and several trials have shown the feasibility of conditioning with clofarabine-based regimen.

      In the past, a conditioning regimen of clofarabine with busulfan (4 doses) has been
      successfully used prior to allogeneic stem cell transplantation for non-remission AML with
      day +30 complete remission rates were 90-100%. However, these patients were transplanted with
      HLA matched donors. This study will examine those patients undergoing haploidentical
      transplantation.

      Achieving a long-term remission is clearly the goal of AML treatment. For this clinical
      trial, the Investigators propose to examine the use of clofarabine pre- haploidentical
      (related) stem cell transplantation for patients who have experienced two induction failures.
      Even in previous Clofarabine/Busulfan4 studies, the Investigators observed a relapse rate of
      about 45% after achieving the first complete remission. With further development of
      molecularly targeted maintenance therapies, reliable protocols to bring these patients into
      the early complete remission will be essential.
    

Trial Arms

NameTypeDescriptionInterventions
Clofarabine 30 mg/m^2ExperimentalClofarabine 30 mg/m^2 IV once a day for 5 days prior to the initiation of the standard conditioning regimen for the stem cell transplant infusion (Day 0). In the event of excessive toxicities related to the clofarabine, a dose de-escalation to 20 mg/m^2 will occur for the next cohort of subjects. Day -14 through Day -10 Clofarabine 30 mg/m^2, Day - 9 Day of rest (no scheduled conditioning medications), Day - 8 Day of rest, Day - 7 Day of rest, Day - 6 Fludarabine 40 mg/m^2 IV and Busulfan 3.2 mg/kg IV, Day - 5 Fludarabine 40 mg/m^2 IV and Busulfan 3.2 mg/kg IV, Day - 4 Fludarabine 40 mg/m^2 IV, Day - 3 Fludarabine 40 mg/m^2 IV, Day - 2 Day of Rest, Day -1 Total Body Irradiation 200 cGys, Day 0 stem cell transplant infusion, Day +3 Cyclophosphamide 50 mg/kg IV, Day +4 Cyclophosphamide 50 mg/kg IV, Day +5 Start G-CSF, Tacrolimus, and MMF
  • Clofarabine
  • Fludarabine
  • Busulfan
  • Cyclophosphamide
  • Granulocyte Colony-Stimulating Factor
  • Tacrolimus
  • Cellcept

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnostic criteria of AML, without having achieved remission after at least 2
             attempts at induction chemotherapy, no attempt of induction if relapsed within 6
             months of induction or no attempt of induction if relapsed after 6 months post
             induction therapy.

          -  Age 18 to 55 years of age.

          -  Planned or scheduled to receive an allogeneic hematopoietic stem cell transplant
             (HSCT) using peripheral blood (PB) or bone marrow (BM) stem cells. Cord blood donor
             cells are not allowed.

          -  Planned or scheduled to receive a standard conditioning regimen consisting of
             Busulfan, Fludarabine, and TBI.

          -  Performance status: Karnofsky ≥ 70% within 28 days of study registration

          -  LVEF ≥ 50% by MUGA or echocardiogram within 28 days of study registration.

          -  FEV1 and FVC ≥ 50% predicted, DLCO (corrected for hemoglobin) ≥ 50% of predicted
             within 28 days of study registration.

          -  Creatinine clearance 60 mL/min/1.73 m^2 within 28 days of study registration

          -  Serum bilirubin less than or equal to 1.5 times upper limit of normal (ULN);

          -  AST/ALT less than or equal to 2.5 times ULN;

          -  Alkaline phosphatase less than or equal to 2.5 times ULN

        Exclusion Criteria:

          -  Known history of non-compliance with medication, scheduled clinic visits, or
             self-care.

          -  In the opinion of the investigator, no appropriate caregivers identified.

          -  HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive

          -  Active infection including Hepatitis B and Hepatitis C.

          -  In the opinion of the physician investigator, uncontrolled medical or psychiatric
             disorders.

          -  In the opinion of the physician investigator, uncontrolled infections, defined as
             positive blood cultures within 72 hours of study entry or evidence of progressive
             infection by imaging studies such as chest CT scan within 14 days of registration.

          -  Active central nervous system (CNS) leukemia.

          -  Prior allogeneic HSCT.

          -  Pregnant or breastfeeding. Women of child bearing potential (WCBP) are required to
             have a negative serum or urine pregnancy test within 7 days of initiation of
             conditioning regimen.
      
Maximum Eligible Age:55 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of complete remission (CR)
Time Frame:30 days
Safety Issue:
Description:Determine the incidence of CR at 30 days (Day +30) post stem cell transplant infusion

Secondary Outcome Measures

Measure:Non-relapse related mortality
Time Frame:100 days
Safety Issue:
Description:Determine the rate of non-relapse related mortality at 100 days post transplant (Day +100)
Measure:Neutrophil engraftment
Time Frame:1 year
Safety Issue:
Description:Rates of engraftment, defined as the first day of Absolute Neutrophil Count (ANC) greater than 500 for the first of three consecutive days
Measure:Incidence of Acute graft-versus-host disease (GVHD)
Time Frame:100 days
Safety Issue:
Description:The incidence of any grade (1-4) of acute GvHD as measured from day of transplantation to Day +100 using the Glucksberg criteria.
Measure:Severity of Acute graft-versus-host disease (GVHD)
Time Frame:100 days
Safety Issue:
Description:The highest grade (1-4) of acute GvHD experienced by participants as measured from day of transplantation to Day +100 using the Glucksberg criteria
Measure:Incidence of Chronic GVHD
Time Frame:1 year
Safety Issue:
Description:The incidence of any grade (1-4) of acute GvHD as measured from Day +100 to Year 1 post-transplantation using the Glucksberg criteria.
Measure:Severity of Chronic GVHD
Time Frame:1 year
Safety Issue:
Description:The highest overall grade (1-4) of chronic GvHD experienced by participants as measured from Day +100 to Year 1 post-transplantation using the Glucksberg criteria

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Milton S. Hershey Medical Center

Trial Keywords

  • Clofarabine
  • Haploidentical stem cell transplantation
  • Non-remission AML

Last Updated

October 29, 2020