Clinical Trial: Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: HLA-mismatched Allogeneic Cellular Therapy (HMMACT) After Chemotherapy in High Risk Acute Myeloid Leukemia

Brief Summary: This phase I trial studies the side effects of donor stem cell transplant in treating patients with high risk acute myeloid leukemia. Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect)

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the feasibility of cytarabine based chemotherapy and human leukocyte antigen (HLA)-mismatched allogeneic cellular therapy (HMMACT) in patients with high risk acute myeloid leukemia (AML), with feasibility measured by induction mortality (IM) and complete response rate.

SECONDARY OBJECTIVES:

I. To obtain preliminary estimates of clinical outcome following cytarabine based chemotherapy and HMMACT in patients with high risk AML, as measured by event free survival (EFS) and overall survival (OS).

II. To further evaluate the safety outcomes of induction and consolidation of cytarabine and HMMACT in terms of serious infections (grade 4), time to recovery of absolute neutrophil counts and platelets and incidence of graft versus host disease (GvHD).

III. To further evaluate the feasibility of this approach in terms of identifying a suitable donor in this elderly population.

IV. To compare in preliminary manner the clinical outcomes of cytarabine and HMMACT in patients with high risk AML as measured by complete response rate (CRR), event free survival (EFS) and overall survival (OS) by donor/recipient HLA-C1 vs C2 pairs.

V. To characterize in a preliminary manner, the numbers of suppressor regulatory T cells (Tregs), T helper 17 cells (Th17), and cytotoxic T cells during pre and post HMMACT treatment, and with clinical outcomes in leukemia.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive mitoxantrone hydrochloride intravenously (IV) on days 1-3 and cytar
Sponsor: University of Southern California

Current Primary Outcome:

  • Induction mortality [ Time Frame: Up to 8 weeks ]
  • Complete remission rate (complete remission [CR] or incomplete remission [CRi]) [ Time Frame: Up to 3 years ]
    Exact 95% confidence intervals will be constructed.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Occurrence of serious infections (grade 4) assessed using National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) v4.0 [ Time Frame: Up to 3 years ]
    Will be summarized in terms of type, severity, attribution, time of onset, duration, reversibility, and outcome.
  • Time to recovery of absolute neutrophil counts (ANC) [ Time Frame: From stem cell infusion to the first of 3 consecutive days in which the ANC is more than 0.5 x 10^9/L, assessed up to 3 years ]
    Will be summarized using cumulative incidence curves.
  • Time to recovery of platelets [ Time Frame: From stem cell infusion until the first of 3 consecutive days in which the platelet count is more than 30 x 10^9/L, assessed up to 3 years ]
    Will be summarized using cumulative incidence curves.
  • Incidence of GvHD [ Time Frame: Up to 3 years ]
    Will be reported in terms of grade, site, and time of onset (for acute GvHD) and whether limited or extensive, and time of onset (for chronic GvHD).
  • Estimate of clinical outcome as measured by event free survival (EFS) [ Time Frame: From the start of induction until documentation of failure to achieve a CR or CRi during induction, initiation of a salvage therapy, disease recurrence/progression (after induction), or death due to any cause, assessed up to 2 years ]
    Kaplan-Meier plots will be used to summarize the EFS observed in this series. The proportion of patients alive and in continuous complete remission will be estimated at 6, 12, 18, and 24 months. 95% intervals will be constructed.
  • Estimate of clinical outcome as measured by overall survival (OS) [ Time Frame: From the start of induction until death due to any cause, assessed up to 2 years ]
    Kaplan-Meier plots will be used to summarize the OS observed in this series. The proportion of patients alive will be estimated at 6, 12, 18, and 24 months. 95% intervals will be constructed.


Original Secondary Outcome: Same as current

Information By: University of Southern California

Dates:
Date Received: February 26, 2013
Date Started: March 6, 2013
Date Completion: March 6, 2019
Last Updated: April 18, 2017
Last Verified: April 2017