Treatment of Elderly AML Patients With Induction Chemotherapy Followed by G-CSF-Mobilized Stem Cells From Haploidentical Related Donors

April 5, 2018 updated by: Memorial Sloan Kettering Cancer Center
The purpose of this study is to test a method of bone marrow transplantation that results in only temporary donor immune function. In other words, the donor immune cells are given in a way that will allow them to attack leukemia briefly before being destroyed by their own immune system, or "rejected." The investigators want to test whether temporary donor immune function is enough to improve the odds of achieving a remission without exposing the patient to the toxicities of a full bone marrow transplant. To do this, the investigators will use standard chemotherapy for AML followed by an infusion of donor stem cells. The donor will be a family member who is haploidentically, or half matched, to the patient such as a child or sibling. Chemotherapy designed to treat AML should not be strong enough to prevent them from rejecting the donor stem cells. The investigators will then follow the patient to see how long the donor stem cells stay in them. The study will test whether this process is feasible and can result in improved chances of obtaining a remission.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 60.
  • Patients with a new diagnosis of histologically confirmed (according to WHO classification 2008) acute myeloid leukemia (either primary or secondary AML) are included.
  • Patients with a diagnosis of myelodysplastic syndrome with >/= 10% bone marrow blasts with no response or progression of disease after at least 4 cycles of a hypomethylating agent (5-azacytiine or decitabine).
  • Patients must have a healthy blood-related donor (parent, child, sibling) willing to undergo apheresis after G-CSF administration.
  • Karnofsky performance status > 70%.
  • Hepatic function - total bilirubin < 2 and, AST < 2.5 x upper limit of normal, unless liver is involved with disease or a history of Gilbert's disease.
  • Renal function - adequate renal function as demonstrated by a serum creatinine <2 mg/dl.
  • LVEF ≥ 50% as determined by echocardiogram or MUGA.
  • Ability to give informed consent.

Donor Eligibility:

  • Donor is blood-related and HLA-haploidentical to the recipient.
  • Donor ≥18 years old
  • Donor has undergone serologic testing for transmissible diseases as per blood banking guidelines for organ and tissue donors. Tests include but are not limited to: HepBsAg, HepBsAb, HepBcAb, HepC antibody, HIV, HTLV I and II, VZV, CMV and VDRL, and West Nile Virus . Donor must have normal negative test results for HIV, HTLV I and II, and West Nile Virus.
  • Donor has a CXR and EKG performed.
  • Donor is not allergic to G-CSF.
  • Donor must be able to undergo leukapheresis
  • Donor is not pregnant.
  • Donor does not have concurrent malignancy or autoimmune disease.
  • Ability to give informed consent.

Exclusion Criteria:

  • Patients with a diagnosis of acute promyelocytic leukemia (according to WHO classification 20080
  • Major surgery or irradiation within two weeks.
  • Previous therapy with cytotoxic agents for AML. Persons with previous treatments for myelodysplasia/myeloproliferation such as hydroxyurea, interferon, hypomethylating agents (5-azacitidine or decitabine), lenalidomide, or JAK/STAT inhibitors may participate but must have >1 week off therapy prior to enrollment.
  • Active CNS disease.
  • Uncontrolled infection.
  • Pregnant or lactating women - they are excluded, given the potential teratogenic effects of chemotherapy and agents used in the therapy.
  • Male and female patients of child-bearing potential unwilling to use effective means of contraception.
  • HIV or HTLV I/II seropositivity.
  • Concurrent active malignancy other than AML requiring therapy.
  • Clinically significant cardiac disease (NY Heart Association Class III or IV) or pulmonary disease.
  • Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests

Donor Exclusion:

  • Donor has cardiac risk factors precluding ability to undergo leukapheresis.
  • Donor has evidence of concurrent malignancy or autoimmune disease.
  • Donor is pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Induction Chemotherapy Followed by G-CSF-Mobilized Stem Cells
This is a single center trial to assess the feasibility of standard induction chemotherapy followed by a single dose of unmanipulated G-PBSC for the treatment of elderly patients with newly diagnosed AML.
Drug: Induction Chemotherapy
Patients with newly diagnosed AML will receive standard induction chemotherapy with daunorubicin and cytarabine (7+3 scheme). Patients who achieve CR may undergo consolidation chemotherapy at the discretion of the treating leukemia physician.
Procedure: G-PBSC Infusion
G-CSF-mobilized peripheral blood cells will be collected from the donors in the Donor Room according to standard MSKCC BMT guidelines. Patients will be infused by infusion of unmanipulated G-PBSC from a haploidentical related donor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Remission (CR)
Time Frame: 4 weeks

Peripheral Blood Counts: The peripheral blood neutrophil count should be ≥1,500/μl (sustained without growth factor support), and the platelets count should be ≥100,000/μl (without transfusion). No circulating blasts (in the absence of growth factor) should be detected.

Bone Marrow Aspirate: The cellularity of the bone marrow should approximate normal. There must be evidence of maturation of all cell lines. The bone marrow aspirate should contain < 5% blasts. Auer rods should not be detected.

Extramedullary Leukemia: Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2015

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

September 1, 2017

Study Registration Dates

First Submitted

August 6, 2015

First Submitted That Met QC Criteria

August 10, 2015

First Posted (Estimate)

August 11, 2015

Study Record Updates

Last Update Posted (Actual)

April 6, 2018

Last Update Submitted That Met QC Criteria

April 5, 2018

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-141

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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