Clinical Trials /

Donor Cellular Therapy After Cytarabine in Treating Patients With Intermediate-Risk Acute Myeloid Leukemia in Remission

NCT02587871

Description:

This phase II trial studies how well donor cellular therapy after cytarabine works in treating patients with intermediate-risk acute myeloid leukemia with a decrease in or disappearance of signs and symptoms of cancer. Donor cellular therapy is a short-term transfusion of cells from a family member who is incompletely matched. The use of these partially matched white blood cells may help improve response to standard chemotherapy (cytarabine) and reduce some of the risks of infection, without a permanent transplant. Drugs used in chemotherapy, such as cytarabine, 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. Giving donor cellular therapy after cytarabine may kill more cancer cells.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Donor Cellular Therapy After Cytarabine in Treating Patients With Intermediate-Risk Acute Myeloid Leukemia in Remission
  • Official Title: HLA-Mismatched Allogeneic Cellular Therapy (Microtransplantation) After Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia < 60 Years

Clinical Trial IDs

  • ORG STUDY ID: 9L-15-2
  • SECONDARY ID: NCI-2015-01671
  • SECONDARY ID: 9L-15-2
  • SECONDARY ID: P30CA014089
  • NCT ID: NCT02587871

Conditions

  • Adult Acute Myeloid Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission

Interventions

DrugSynonymsArms
Cytarabine.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453Treatment (cytarabine, G-CSF mobilized peripheral blood cells)
Therapeutic Allogeneic LymphocytesAllogeneic Lymphocytes, Tumor-Derived LymphocyteTreatment (cytarabine, G-CSF mobilized peripheral blood cells)
G-CSF mobilized peripheral blood cellsFilgrastimTreatment (cytarabine, G-CSF mobilized peripheral blood cells)

Purpose

This phase II trial studies how well donor cellular therapy after cytarabine works in treating patients with intermediate-risk acute myeloid leukemia with a decrease in or disappearance of signs and symptoms of cancer. Donor cellular therapy is a short-term transfusion of cells from a family member who is incompletely matched. The use of these partially matched white blood cells may help improve response to standard chemotherapy (cytarabine) and reduce some of the risks of infection, without a permanent transplant. Drugs used in chemotherapy, such as cytarabine, 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. Giving donor cellular therapy after cytarabine may kill more cancer cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess 2-year disease-free survival (as defined by time to death from any cause or
      disease relapse, whichever is earlier) for patients < 60 years of age with intermediate-risk
      acute myeloid leukemia (AML), in complete remission (CR) after induction chemotherapy, who
      receive microtransplantation, compared to patients who received consolidation chemotherapy
      only in a historical published comparable cohort of patients.

      SECONDARY OBJECTIVES:

      I. To obtain estimates of rate of relapse, treatment related mortality (TRM), all cause
      mortality, in the microtransplantation (MST) group and compare it with allogeneic stem cell
      group (historical cohort).

      II. To obtain estimates of rate acute graft-versus-host disease (GVHD), chronic GVHD, time to
      recovery of absolute neutrophil counts and platelets in patients with intermediate risk AML
      receiving of chemotherapy in combination with microtransplantation.

      TERTIARY OBJECTIVES:

      I. Presence or absence of detectable donor chimerism post-microtransplantation until 6 months
      after the last infusion.

      II. Characteristics of the infused cells and composition of the graft. III. Dynamics of
      T-cell clonality. IV. Immune cell subset analysis.

      OUTLINE:

      Approximately 4-6 weeks after completion of induction chemotherapy, patients receive
      cytarabine intravenously (IV) over 1-3 hours twice daily (BID) on days -7 to -2 and
      granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood cells
      (microtransplant) IV over 15-20 minutes on day 0. Treatment repeats every 8-10 weeks for 3
      courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at least every 3 months for 2
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cytarabine, G-CSF mobilized peripheral blood cells)ExperimentalApproximately 4-6 weeks after completion of induction chemotherapy, patients receive cytarabine IV over 1-3 hours BID on days -7 to -2 and G-CSF mobilized peripheral blood cells (microtransplant) IV over 15-20 minutes on day 0. Treatment repeats every 8-10 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
  • Cytarabine

Eligibility Criteria

        Inclusion Criteria:

          -  PATIENT INCLUSION CRITERIA:

          -  Acute myeloid leukemia-intermediate risk as defined by standard World Health
             Organization (WHO) criteria for AML (at least 20% blasts in the peripheral blood or
             bone marrow) at the time of initial diagnosis

               -  Diagnosis of AML according to WHO diagnostic criteria (at least 20% blasts in the
                  peripheral blood or bone marrow), with French-American-British (FAB)
                  classification other than M3 (acute promyelocytic leukemia), documented by bone
                  marrow aspiration and biopsy performed within 14 days prior to administration of
                  1st dose of remission induction chemotherapy

          -  Intermediate risk based on National Comprehensive Cancer Network (NCCN)

          -  In CR or complete remission with incomplete blood count recovery (CRi) after 1-2
             induction chemotherapy documented by a bone marrow examination done within 2 weeks of
             starting cytarabine in this protocol

          -  Must have achieved CR/CRi with less than 2 induction regimens that contain cytarabine
             and anthracycline

          -  No 10/10 matched sibling donor available or not financially eligible for allogeneic
             stem cell transplantation

          -  Must be within 3 months from the last induction regimen at the time of starting
             cytarabine chemotherapy in this protocol

          -  Patient has at least one medically fit first- or second-degree family member expected
             to be human leukocyte antigen (HLA) mismatched at 2-9/10 loci; in addition, the
             prospective donor is willing to voluntarily donate hematopoietic stem cells and sign
             consent forms

          -  Absolute neutrophil count (ANC) > 1500, unless due to direct bone marrow involvement
             of disease

          -  Platelets > 75,000, unless due to direct bone marrow involvement of disease

          -  Hemoglobin > 8.0 gm/dL, transfusion allowed

          -  Serum creatinine < 2.0 x the upper limits of institutional normal (ULN)

          -  Total bilirubin < 1.5 x the upper limits of institutional normal

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x the upper
             limits of institutional normal (=< 5 x ULN for patients with suspected liver
             involvement of leukemia)

          -  Cardiac left ventricular ejection fraction (LVEF) > 45%

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, and
             estimated survival of at least 3 months

          -  Patients must be able to understand and agree to sign an Institutional Review Board
             (IRB)-approved informed consent form

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control) prior to study entry, for the duration
             of study, and for two months after study participation; should a woman become pregnant
             or suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately

          -  DONOR INCLUSION CRITERIA:

          -  Donor screening; all donors will meet the standard blood donor criteria established by
             the participating local blood center, American Association of Blood Banks (AABB)

          -  Donors will be selected from among the subject's relatives, adult children preferred

          -  Infectious disease testing will be done per Hemacare policy and AAAB guidelines

          -  Donor and intended recipient red cell type and compatibility will be determined

          -  Donors will be pre-selected on the basis of HLA haploidentity

          -  If patient is cytomegalovirus (CMV)-negative, donors who are CMV-negative will be
             preferred; CMV serology of the donor will be tested prior to the allogeneic cell
             donation; donations from CMV-positive donors to CMV-negative recipients will be given
             if no CMV negative donor is available, and CMV surveillance and pre-emptive treatment
             given as per guidelines below

        Exclusion Criteria:

          -  PATIENT EXCLUSION CRITERIA:

          -  Acute promyelocytic leukemia

          -  High risk AML (see NCCN risk criteria)

          -  Low risk AML (see NCCN risk criteria)

          -  Fludarabine based therapy within 6 months of enrollment

          -  Uncontrolled intercurrent 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

          -  Who are pregnant and/or lactating

          -  Who have had non-biopsy surgery in the last 10 days

          -  Who have active central nervous system (CNS) disease; patients with previously treated
             leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid
             will be eligible

          -  Patients with known active autoimmune disorder

          -  Patients known to be have active hepatitis B or C; (hepatitis B positive patients are
             allowed if they are on appropriate antiviral agents such as lamivudine)

          -  Patients concurrently taking the following drugs are excluded: mycophenolate,
             cyclosporine, prednisone > 20 mg/day, or immunosuppressive agents

          -  Researchers think that any life-threatening illness, condition or organ system
             dysfunction can damage the safety of subjects

          -  Failure to demonstrate adequate compliance with medical therapy and follow-up

          -  DONOR EXCLUSION CRITERIA:

          -  Personal or family history of severe sickle cell disease or variant (unless donor has
             tested negative); testing for the presence of hemoglobin S is not required

          -  Positive infectious disease test as dictated by blood collection center's standard
             operating procedure (SOP)

          -  Current uncontrolled hypertension

          -  Pregnant or breast-feeding

          -  Currently taking lithium therapy

          -  History of autoimmune disease
      
Maximum Eligible Age:59 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease free survival (DFS)
Time Frame:Beginning of therapy to the date of death or the date of last follow-upexamination, assessed at 2 years
Safety Issue:
Description:The 2-year DFS will be estimated, and the corresponding 90% confidence intervals will be constructed. The data will be displayed using a Kaplan-Meir curve to plot the DFS over time. Calculate bilateral 95% confidential interval of mean difference of disease-free survival rate, and compare the lower limit of the bilateral 95% confidential interval and 15% superiority boundary value.

Secondary Outcome Measures

Measure:Cumulative incidence acute GVHD, classified as clinically significant (grades 2 to 4) or severe (grades 3 to 4)
Time Frame:6 months after microtransplant
Safety Issue:
Description:At single time point, if univariate quantitative data of the meets the normal distribution and homogeneity of variance, perform test of univariate quantitative data, otherwise, adopt the rank-sum test of corresponding design; for univariate quantitative data under multiple time points, use mixed effects model to design variance analysis with repeated measure factors.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Southern California

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