IPA Targeted Adoptive Immunotherapy vs Adult Haplo-identical Cell Infusion During Induction of High Risk Leukemia

Study Description

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Brief Summary:

The purpose of this study is to determine the overall safety of adoptive immunotherapy when given after chemotherapy for AML/MDS. Adoptive immunotherapy means using an infusion of cells from a donor to help fight cancer. The donor cells will be either from the umbilical cord blood (UCB) of a newborn baby or they will be cells collected from a relative (haplo-identical cells).

The 2 cohorts that were discussed - adoptive immunotherapy with either UCB or haplo-identical stem cells - will be analyzed separately.

Preliminary data from other centers has suggested that adoptive immunotherapy with cells from a relative is an effective approach that may improve remission rates and survival in AML and MDS, because they exert anti-cancer effects of their own (so called graft vs leukemia effects) and possibly because they hasten recovery of cell counts from chemotherapy. The Investigators are interested in confirming these data, but also in testing umbilical cord blood cells for the same purpose. Preliminary data indicate that umbilical cord blood cells may have more powerful graft vs leukemia effects and cause fewer side-effects.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia; Myelodysplastic Syndrome	Biological: haplo-identical cells (donor); Biological: umbilical cord blood unit (CBU)	Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Parallel Phase II Trial of IPA Targeted Adoptive Immunotherapy vs Adult Haplo-identical Cell Infusion During Induction of High Risk Leukemia
Actual Study Start Date :	September 10, 2015
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	December 2020

Arms and Interventions

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Arm

Intervention/treatment

Intervention; All potential recipients will have complete (HLA) typing and determination of HLA antibodies. An appropriate umbilical cord blood unit (CBU) will be identified or in the absence of an appropriate CBU, a haplo-identical cells (donor) will be identified. Within 72 hours after completion of the chemotherapy regimen, and no sooner than 24 hours after administration of the last dose of chemotherapy, umbilical cord graft or haplo-graft will be administered.

Biological: haplo-identical cells (donor); Treatment: Haplo-identical healthy related donor. i.e. Parent, child, sibling, possibly third degree or further removed relative (cousin, aunt, nephew etc). They will be collected using standard methods and approximately 3 x10^6 CD34 cells/kg will be infused within 72 hours after completion of the treatment. Biological: umbilical cord blood unit (CBU); Treatment: The CBU unit must supply a minimum of 0.5 x107/kg and a maximum of 2.5x107/kg nucleated cell dose pre-cryopreservation. The unit must match at a minimum of 4 of 6 at HLA-A, -B antigens, -DRB1 alleles with the recipient. Mismatches (0-2) can be at any loci -. Although molecular level typing will be available for the patient and the CBU unit, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1. The CBU donor will also have undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA. CBU grafts used in this study will be investigational units that meet all criteria for clinical use. Better matching units will be preferred over less matching units as long as the CBU dose exceeds 0.5 x107 nucleated blood cells/kg

Outcome Measures

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Primary Outcome Measures :

1. Safety of cellular immunotherapy [ Time Frame: 6 months ]
   evaluate the safety of adoptive immunotherapy with Non-Inherited Maternal Antigen (NIMA) compatible, Inherited Paternal Antigen (IPA) targeted CBU or with haplo-identical stem cells after conventional induction therapy for very high risk AML or MDS.

Secondary Outcome Measures :

1. Incidence of Graft Versus Host Disease (GVHD) <10% [ Time Frame: 6 months ]
   To assess the incidence and severity of Graft Versus Host Disease (GVHD), after conventional induction therapy followed by adoptive immunotherapy with NIMA compatible, IPA targeted CBU.
2. Detection of graft chimerism after infusion [ Time Frame: 6 months ]
   To study kinetics of graft chimerism (including umbilical cord blood-microchimerism) after each of these treatments
3. Detection of HLA-antibodies after after infusion <10% [ Time Frame: 6 months ]
   To study development of HLA-antibodies after each of these treatments
4. The response rate of leukemia [ Time Frame: 6 months ]
   To assess response rates and duration of response after each of these treatments

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Patients must be 18 years of age or older

2. Patients with a confirmed diagnosis of AML or MDS, according to World Health Organization (WHO) classification (excluding acute promyelocytic leukaemia) with recurrent or refractory disease as defined below.

   1. For AML:

      1. Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy.
      2. First relapse.
      3. Relapse refractory to salvage chemotherapy
      4. Second or subsequent relapse.
   2. For MDS, either refractory anemia with excess blasts (RAEB) I or RAEB II who failed at least one chemotherapy regimen including either cytarabine or a hypomethylating agent.
3. Patients must have Karnofsky Performance score of ≥70
4. Women of child-bearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to treatment start
5. Patients must be capable of understanding and complying with protocol requirements, and must be able and willing to sign a written informed consent form

Exclusion Criteria:

1. Persistent clinically significant toxicities from previous chemotherapy
2. Known positive status for human immunodeficiency virus (HIV)
3. Pregnant and nursing patients
4. Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
5. Impairment of hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into this clinical study
6. Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure. Any New York Heart Association (NYHA) grade 3 or 4.
7. Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities

Contacts and Locations

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Contacts

Contact: June Greenberg	212-746-2651	jdg2002@med.cornell.edu
Contact: Koen van Besien, MD	(212) 746-2048	kov9001@med.cornell.edu

Locations

United States, New York
Weill Cornell Medical College	Recruiting
New York, New York, United States, 10021
Contact: June Greenberg, RN 212-746-2651 jdg2002@med.cornell.edu
Sub-Investigator: Roboz Gail, MD
Sub-Investigator: Mayer Sebastian, MD
Sub-Investigator: Ritchie Ellen, MD
Sub-Investigator: Shore Tsiporah, MD

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

Principal Investigator:	Koen van Besien, MD	Weill Medical College of Cornell University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT02508324 History of Changes
Other Study ID Numbers:	1403014939
First Posted:	July 24, 2015
Last Update Posted:	January 9, 2018
Last Verified:	January 2018

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Preleukemia; Neoplasms by Histologic Type	Neoplasms; Leukemia, Myeloid; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions