Clinical trial NCT02519712: Treatment of Elderly AML Patients With Induction Chemotherapy Followed by G-CSF-Mobilized Stem Cells From Haploidentical Related Donors
Official title: Treatment of Elderly AML Patients With Induction Chemotherapy Followed by G-CSF-Mobilized Stem Cells From Haploidentical Related Donors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Induction Chemotherapy
G-CSF-Mobilized Stem Cells
Haploidentical Related Donors
15-141
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2015-08-11
Enrollment: 4
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete Remission (CR)
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Brian Shaffer, MD
role: PRINCIPAL_INVESTIGATOR
References: