Mismatched Donor Cells to Treat Acute Myeloid Leukemia

NCT01793025 | Unknown Phase 1

• 1 other identifier: ATAC-AML-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and efficacy of infusing immune cells from a donor as treatment for patients with acute myeloid leukemia that is resistant to chemotherapy or who have experienced relapse. Unlike standard bone marrow or stem cell transplantation which uses donors who are well 'matched' to the patient, this study uses donors whose immune cells are not compatible with the patient. With standard stem cell or bone marrow transplantation, the well-matched immune cells will attack the leukemia but they also attack the patient's organs (a situation called graft-versus-host disease, which can persist in the long term). Our hypothesis is that the mismatched donor cells will fight the leukemia but will then be eliminated from the patient's body, so long-term side effects like graft-versus-host disease should not occur.

Conditions

Acute Myeloid Leukemia

Keywords

leukemia; myeloid; acute; acute myeloid leukemia; allogeneic; transient chimerism; cell therapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Safety

  Maximum tolerated cell dose: Dose at which \< 33% of patients experienced dose-limiting toxicity. If no DLT occurs, then dose titration will stop at a pre-specified number of T cells/kg. Four dose-level cohorts are planned.

  60 days (up to 2 years)

Secondary Outcomes (7)

• Treatment-related mortality

  Continuous up to 2 years

• Non-relapse mortality

  Continuous up to 2 years

• Incidence of graft-versus-host disease

  Continuous up to 2 years

• Duration of cytopenias

  Monitored continuously from ATAC infusion until peripheral blood count recovery or maximum 2 years (whichever is earlier)

• Overall survival

  Continuous up to 2 years

Study Arms (1)

ATAC Therapy

EXPERIMENTAL

Biological: ATAC Therapy

Interventions

ATAC Therapy BIOLOGICAL

Unselected peripheral blood mononuclear cells given 24-48 hours after induction or consolidation chemotherapy

Also known as: Unselected Peripheral Blood Mononuclear Cells

ATAC Therapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years (no upper age limit, but physician discretion is advised)
• AML that is refractory to 2 courses of induction therapy (that together constitute the 'first-line' therapy) or that has relapsed after a period of morphologic complete remission or morphologic remission with incomplete blood count recovery (CRi)
• Candidacy for intense induction chemotherapy (ECOG 0-2, adequate renal, liver and cardiac function, absence of uncontrolled infections)
• Availability of parents, siblings or children who are HLA haploidentical (and not homozygous for the shared haplotype), who are deemed suitable donors after medical evaluation, and who complete peripheral blood mononuclear cell collection
• No history of autologous or allogeneic stem cell transplant, purine analog chemotherapy or cyclophosphamide, or total body irradiation
• Ability to comprehend the investigational nature of the study and provide informed consent

You may not qualify if:

• Acute promyelocytic leukemia (including those with non-classical rearrangements of RARα)
• Grade 2-3/3 fibrosis in the diagnostic bone marrow biopsy
• DLCO \< 40% predicted
• Left ventricular ejection fraction \< 40% (evaluated by ECHO or MUGA)
• AST/SGOT \> 2.5 x ULN
• Bilirubin \> 1.5 x ULN
• Creatinine \> 1.5 x ULN
• Creatinine clearance \< 50 mL/min
• HIV positive
• Major anticipated illness or organ failure incompatible with survival from chemotherapy
• Concurrent second primary cancer or a prior malignancy that required cytotoxic treatment within the past 12 months, other than cervical carcinoma in-situ or prostate cancer in-situ
• Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the treatment unlikely and informed consent impossible
• Any congenital or acquired immunodeficiency that would possibly permit permanent engraftment of donor cells
• Receiving systemic steroid therapy or systemic immunosuppression such as cyclosporine or TNF-inhibitors
• Prior or concurrent receipt of any marketed or investigational agent deemed on an ad hoc basis to cause immunomodulation, pose a threat of permanent engraftment or increase the risk of GVHD.

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead

Study Sites (1)

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 3M4, Canada

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Jean-Sébastien Delisle, MD,PhD

  Hôpital Maisonneuve-Rosemont and Université de Montréal

  STUDY CHAIR

• Elizabeth Krakow, MD

  Hôpital Maisonneuve-Rosemont and Université de Montréal

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-Sébastien Delisle, MD,PhD

CONTACT

(514) 252-3404; js.delisle@umontreal.ca

Jean Morin

CONTACT

(514) 252-3404; jmorin.hmr@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fellow, Hematopoietic Cell Transplantation

Study Record Dates

• First Submitted: February 10, 2013
• First Posted: February 15, 2013
• Study Start: September 1, 2012
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: August 30, 2017

Record last verified: 2017-08

Locations

CA (1)