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

NCT02587871 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: 9L-15-2NCI-2015-01671P30CA014089
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adult Acute Myeloid Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission

Outcome Measures

Primary Outcomes (1)

• Disease free survival (DFS)

  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.

  Beginning of therapy to the date of death or the date of last follow-upexamination, assessed at 2 years

Secondary Outcomes (1)

• Cumulative incidence acute GVHD, classified as clinically significant (grades 2 to 4) or severe (grades 3 to 4)

  6 months after microtransplant

Study Arms (1)

Treatment (cytarabine, G-CSF mobilized peripheral blood cells)

EXPERIMENTAL

Approximately 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.

Drug: Cytarabine; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Biological: Therapeutic Allogeneic Lymphocytes; Biological: G-CSF mobilized peripheral blood cells

Interventions

Cytarabine DRUG

Given IV

Also known as: .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-28453

Treatment (cytarabine, G-CSF mobilized peripheral blood cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cytarabine, G-CSF mobilized peripheral blood cells)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo microtransplant

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (cytarabine, G-CSF mobilized peripheral blood cells)

Therapeutic Allogeneic Lymphocytes BIOLOGICAL

Undergo microtransplant

Also known as: Allogeneic Lymphocytes, Tumor-Derived Lymphocyte

Treatment (cytarabine, G-CSF mobilized peripheral blood cells)

G-CSF mobilized peripheral blood cells BIOLOGICAL

microtransplantation

Also known as: Filgrastim

Treatment (cytarabine, G-CSF mobilized peripheral blood cells)

Eligibility Criteria

• Age: Up to 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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%

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Interventions

Cytarabine; Peripheral Blood Stem Cell Transplantation; Filgrastim

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Giridharan Ramsingh

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: October 27, 2015
• Study Start: December 12, 2018
• Primary Completion: November 12, 2020
• Study Completion: November 12, 2022
• Last Updated: November 9, 2018

Record last verified: 2018-11

Locations

US (1)