CD3-/CD19- vs CD3-/CD56+ Haplo NK for AML Pts Who Failed 1-2 Inductions

Acute Myelogenous Leukemia Clinical Trial

Official title:

A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for Adults With Acute Myelogenous Leukemia Who Have Failed 1 or 2 Induction Attempts

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03290664
• Other study ID #: 2014LS005
• Secondary ID: MT2014-02
• Status: Terminated
• Phase: Phase 2
• Start date: October 18, 2017
• Est. completion date: February 13, 2019

Study information

• Verified date: April 2019
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase II trial of related donor HLA-haploidentical NK-cell based therapy for the treatment of newly diagnosed acute myelogenous leukemia (AML) (except acute promyelocytic leukemia) in persons who failed to achieve a complete remission (CR) after one or two standard induction attempts. Failure is defined as ≥ 30% bone marrow blasts in a bone marrow of at least 20% cellularity at the mid-cycle (~day 14) bone marrow biopsy or residual AML on ~day 28 bone marrow biopsy by morphology, flow, PCR or FISH.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: February 13, 2019
• Est. primary completion date: February 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Newly diagnosed with acute myelogenous leukemia (except acute promyelocytic leukemia) and has failed one or two prior standard induction attempts. Failure is defined as:

• = 30% bone marrow blasts in a bone marrow with at least 20% cellularity at mid-cycle bone marrow biopsy or

• residual AML on ~ day 28 bone marrow biopsy by morphology, flow, PCR or FISH

• AML that progressed out of myelodysplastic syndrome (MDS) is eligible if the patient did not receive treatment directed at the MDS.

• Patients enrolling after only 1 failed induction attempt must meet at least one of the following additional eligibility criteria of high risk:

• = 60 years of age

• adverse cytogenetics or molecular characteristics

• (inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1

• t(6;9)(p23;q34); DEK-NUP214

• t(v;11)(v;q23); MLL rearranged

• -5 or del(5q); -7; abnl(17p); complex karyotype

• Persons receiving a "non-standard" induction (i.e. one containing investigational agent(s)) will be considered for eligibility by Miltenyi on a case by case basis.

• Use of hydroxyurea is permitted to control blasts until the day chemotherapy is started.

• A history of AML related CNS involvement is allowed if most recent CSF analysis is negative at least 2 weeks prior to study treatment.

• = 18 and <75 years of age

• Karnofsky performance status = 60% (appendix IV)

• HLA-haploidentical related donor (aged 12 to 70 years) with donor/recipient match based on a minimum of intermediate resolution DNA based Class I typing of the A,B and C locus - refer to section 5 for donor selection.

• Adequate organ function within 14 days of study registration (30 days for pulmonary and cardiac) defined as:

• Creatinine: = 2.0 mg/dL

• Hepatic: SGOT and SGPT < 5 x upper limit of institutional normal (ULN)

• Pulmonary: oxygen saturation = 90% on room air

• Cardiac: LVEF = 40% by echocardiogram, MUGA or cardiac MRI, no uncontrolled angina, uncontrolled atrial or ventricular arrhythmias, or evidence of acute ischemia or active conduction system abnormalities (rate controlled a-fib is not an exclusion)

• Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the NK cell infusion (excluding preparative regimen pre-meds)

• Sexually active females of childbearing potential and males with partners of child bearing potential must agree to use appropriate birth control precautions during the study and for 3 months after the NK cell infusion

• Voluntary written consent prior to the performance of any research related procedures

Exclusion Criteria:

• Pregnant or lactating as the treatments used in this study includes drugs that are FDA Pregnancy Category D - Positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans. Women of child bearing potential must have a negative pregnancy test within 14 days of study registration.

• Acute leukemias of ambiguous lineage

• AML that transformed from previously treated myelodysplastic syndromes

• Untreated CNS leukemia

• Prior hematopoietic transplant

• New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been cleared by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)

• Uncontrolled bacterial, fungal, or viral infections including HIV - chronic asymptomatic viral hepatitis is allowed

• Known hypersensitivity to one or more of the study agents

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• CD3-/CD19-
CD3-/CD19- will be infused along with IL-2 on Day 0 following a preparative regimen of Fludarabine and Cyclophosphamide.
• CD3-/CD56+
CD3-/CD56+ will be infused along with IL-2 on Day 0 following a preparative regimen of Fludarabine and Cyclophosphamide.

Locations

Country	Name	City	State
United States	University of Minnesota, Masonic Cancer Center	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota	Miltenyi Biotec, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Remission	Incidence of complete remission which is defined as the following disease statuses: absolute neutrophil count > 1,000/mm3, platelet count > 100,000/ mm3, no leukemic blast in the peripheral blood and < 5% blast in the marrow (CR),; a morphologic complete remission with incomplete blood count recovery (CRi); leukemia clearance (< 5% marrow blast and no circulating peripheral blasts) and neutrophil recovery but with incomplete platelet recovery (CRp)	Day 42
Secondary	NK Cell Expansion/Persistence	Defined as = 100 donor derived NK cells per µl blood	Day 42
Secondary	Treatment Related Adverse Events	Incidence of treatment related adverse events	Day 42
Secondary	Infusional Toxicities	Incidence of infusional toxicities	Day 42
Secondary	Treatment related mortality	Incidence of treatment related mortality	Day 100
Secondary	Proceeding to hematopoietic cell transplantation	Incidence subjects eligible to proceeding to hematopoietic cell transplantation. Eligibility is defined by having a remission status as defined in the primary outcome.	3 months
Secondary	aGvHD	Incidence of acute graft versus host disease (aGvHD)	Day 42
Secondary	Overall survival at 12 months	Incidence of overall survival	12 months
Secondary	Overall survival at 24 months	Incidence of overall survival	24 months
Secondary	Disease free survival at 12 months	Incidence of disease free survival	12 months
Secondary	Disease free survival at 24 months	Incidence of disease free survival	24 months