Loading clinical trials...

TERMINATEDPHASE2

T-Cell Depleted Double UCB for Refractory AML

T-Cell Depleted Double UCB With Post Transplant IL-2 for Refractory Myeloid Leukemia

NCT01464359•Masonic Cancer Center, University of Minnesota

Summary

This trial is proposes to build on our experience and is designed to maximize early (day 3-14) and late (day 60-71) donor-derived natural killer (NK) cell expansion and function in vivo. The proposed platform will allow us the unique opportunity to compare in vivo function from a transplanted umbilical cord blood (UCB) source (presumed to contain NK progenitors requiring "education" in the recipient).

Detailed Description

This single center study will determine the feasibility and safety of using a myeloablative conditioning regimen followed (on day 0) by transplantation with double T-cell depleted (TCD) umbilical cord blood (UCB) units where the unit with fewer mononuclear cells (MNCs)/kg will be selected for overnight IL-2 activation prior to infusion. Beginning on day +3, post transplant IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses to expand UCB derived progenitor cells. Post transplant immune suppression prophylaxis will not be administered with the intent to lessen toxicity and allow allogeneic NK cells to function longer providing better anti-leukemic therapy. However if either UCB unit has more than 5% T-cells, the patient will not receive either course of IL-2. Beginning on day +60 after transplantation, a second course of IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses with the purpose of enhancing the in vivo expansion and education of NK cells derived from engrafting UCB cells.

Eligibility

Age

2 - 45 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Aged 2 to 45 years with acute myeloid leukemia (AML) who meet one of the following criteria:
•* Primary induction failure defined as no complete remission (CR) after two or three induction cycles (no blast limit).
•* Relapsed AML with low disease burden: For patients \>21 through 45 years of age: must have \<30% marrow blasts within 14 days of enrollment and be at least 28 days from the start of last therapy. For patients 2 through ≤ 21 years of age: must have \>5% marrow blasts after no more than 3 induction attempts.
•Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and is in remission. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the protocol.
•Have acceptable organ function within 14 days of study registration defined as:
•* Renal: creatinine ≤ 2.0 mg/dL (adult patients) or calculated creatinine clearance \> 40 ml/min (pediatric patients)
•* Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 5 times upper limit of normal
•* Pulmonary function: diffusing lung capacity for carbon monoxide corrected for hemoglobin (DLCOcorr) \> 50% of normal, (oxygen saturation \[\>92%\] can be used in child where pulmonary function tests (PFT's) cannot be obtained)
•* Cardiac: left ventricular ejection fraction ≥ 45%
•Karnofsky Performance Status ≥ 70% (≥ 16 years) or Lansky Play Score ≥ 50 (pediatrics \< 16 years)
+3 more criteria

Exclusion Criteria

•Active infection at time of enrollment or documented fungal infection within 3 months unless clearance from Infectious Disease
•Evidence of HIV infection or known HIV positive serology
•Pregnant or breast feeding.
•If \< or = 21 years old, prior myeloablative transplant within the last 6 months. If \> 21 years old prior myeloablative allotransplant or autologous transplant - if prior conditioning regimen included total body irradiation (TBI), then busulfan/cyclophosphamide(BU/CY) prep should be used
•If \> 21 years old - extensive prior therapy including \> 12 months of any alkylator chemotherapy (etoposide \>100 mg/m\^2 x 5 days, cyclophosphamide \>1 gm/m\^2 or mitoxantrone \>8 gm/m\^2) delivered at 3-4 week intervals or \> 6 months alkylator therapy (as above) with extensive radiation (determined by Radiation Oncology, e.g. mantle irradiation for Hodgkin's) and/or prior radiation therapy that makes a patient ineligible for TBI.
•Known hypersensitivity to any of the study agents

Locations (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Key Dates

Start Date

October 1, 2011

Primary Completion Date

October 1, 2013

Completion Date

October 1, 2013

Last Updated

December 28, 2017

Enrollment

ACTUAL participants

Conditions

Acute Myelogenous LeukemiaRefractory Acute Myelogenous Leukemia

Interventions

Allopurinol

DRUG

Fludarabine

DRUG

Total body irradiation

RADIATION

Cyclophosphamide

DRUG

Levetiracetam

DRUG

Busulfan

DRUG

Umbilical Cord Blood Transplantation

BIOLOGICAL

Interleukin-2

BIOLOGICAL

A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

NCT06859424

AML (Acute Myelogenous Leukemia)Acute Lymphoid Leukemia (ALL)+9 more

View study

RECRUITING

Correlation of Venetoclax Plasma Concentrations With Toxicity of Hypometilating Agents and Venetoclax Combination for Acute Myeloid Leukemia Patients in Remission.

NCT07254312

AML (Acute Myelogenous Leukemia

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: December 28, 2017Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

T-Cell Depleted Double UCB for Refractory AML

Inclusion Criteria

Exclusion Criteria

A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Correlation of Venetoclax Plasma Concentrations With Toxicity of Hypometilating Agents and Venetoclax Combination for Acute Myeloid Leukemia Patients in Remission.

HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

Avapritinib Combined With Azacitidine and Venetoclax in the Treatment of Relapsed AML After Allo-HSCT

Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

PRO#1278: Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation