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

NCT02508324 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 1403014939
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Safety of Cellular Immunotherapy as Measured by the Number of Participants Who Developed of Cytokine Release Syndrome (CRS) or Graft-versus-host Disease (GVHD) After Adoptive Immunotherapy

  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. Assessed by development of cytokine release syndrome (CRS) or graft-versus-host disease (GVHD) after adoptive immunotherapy.

  6 months

Secondary Outcomes (5)

• Number of Participants Who Developed GVHD by Severity

  6 months

• Number of Participants With Detectable Cord Blood or Haploidentical Chimerism After Adoptive Immunotherapy

  6 months

• Number of Participants With HLA-antibodies That Precluded Them From Moving Forward to Transplant

  6 months

• Number of Participants Who Responded to Treatment

  6 months

• Number of Participants That Underwent a Transplant After Response to Adoptive Immunotherapy

  6 months

Study Arms (2)

Cord Blood Unit

OTHER

The CBU unit must supply a minimum of 0.5 x 10\^7/kg and a maximum of 2.5 x 10\^7/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 have also undergone HLA typing of the mother, thus allowing determination of the CBU-IPA and NIMA. CBU grafts 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 x 10\^7 nucleated blood cells/kg.

Biological: umbilical cord blood unit (CBU)

Haploidentical

OTHER

Haploidentical healthy related donor (i.e. parent, child, sibling, possibly third degree or farther removed relative like cousin, aunt, nephew etc.). Collected using standard methods and approximately 3 x10\^6 CD34 cells/kg will be infused within 72 hours after completion of treatment.

Biological: haplo-identical cells (donor)

Interventions

haplo-identical cells (donor) BIOLOGICAL

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.

Haploidentical

umbilical cord blood unit (CBU) BIOLOGICAL

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

Cord Blood Unit

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be 18 years of age or older
• 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.
• For AML:
• Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy.
• First relapse.
• Relapse refractory to salvage chemotherapy
• Second or subsequent relapse.
• 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.
• Patients must have Karnofsky Performance score of ≥70
• Women of child-bearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to treatment start
• Patients must be capable of understanding and complying with protocol requirements, and must be able and willing to sign a written informed consent form

You may not qualify if:

• Persistent clinically significant toxicities from previous chemotherapy
• Known positive status for human immunodeficiency virus (HIV)
• Pregnant and nursing patients
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
• 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
• 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.
• Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• New York Blood Center: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Publications (1)

• Chaekal OK, Scaradavou A, Masson Frenet E, Albano MS, Cushing M, Desai P, Dobrila L, Gergis U, Guarneri D, Hsu JM, Lee S, Mayer SA, Phillips AA, Orfali N, Ritchie EK, Roboz GJ, Romeo C, Samuel MS, Shore T, van Besien K. Adoptive immunotherapy with CB following chemotherapy for patients with refractory myeloid malignancy: chimerism and response. Blood Adv. 2020 Oct 27;4(20):5146-5156. doi: 10.1182/bloodadvances.2020002805.

  PMID: 33091124 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Results Point of Contact

• Title: Alexandra Gomez Arteaga, MD
• Organization: Weill Cornell Medicine

alg9117@med.cornell.edu

646-962-7950

Study Officials

• Alexandra Gomez Arteaga, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 7, 2015
• First Posted: July 24, 2015
• Study Start: September 10, 2015
• Primary Completion: June 24, 2022
• Study Completion: June 24, 2022
• Last Updated: February 13, 2024
• Results First Posted: February 13, 2024

Record last verified: 2024-01

Locations

US (1)