Description:
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.
Title
- Brief Title: CD3-/CD19- vs CD3-/CD56+ Haplo NK for AML Pts Who Failed 1-2 Inductions
- 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 IDs
- ORG STUDY ID:
2014LS005
- SECONDARY ID:
MT2014-02
- NCT ID:
NCT03290664
Conditions
- Acute Myelogenous Leukemia
Interventions
Drug | Synonyms | Arms |
---|
CD3-/CD19- | | CD3-/CD19- Infusion |
CD3-/CD56+ | | CD3-/CD56+ Infusion |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
CD3-/CD19- Infusion | Experimental | | |
CD3-/CD56+ Infusion | Experimental | | |
Eligibility Criteria
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
Maximum Eligible Age: | 74 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Complete Remission |
Time Frame: | Day 42 |
Safety Issue: | |
Description: | 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) |
Secondary Outcome Measures
Measure: | NK Cell Expansion/Persistence |
Time Frame: | Day 42 |
Safety Issue: | |
Description: | Defined as ≥ 100 donor derived NK cells per μl blood |
Measure: | Treatment Related Adverse Events |
Time Frame: | Day 42 |
Safety Issue: | |
Description: | Incidence of treatment related adverse events |
Measure: | Infusional Toxicities |
Time Frame: | Day 42 |
Safety Issue: | |
Description: | Incidence of infusional toxicities |
Measure: | Treatment related mortality |
Time Frame: | Day 100 |
Safety Issue: | |
Description: | Incidence of treatment related mortality |
Measure: | Proceeding to hematopoietic cell transplantation |
Time Frame: | 3 months |
Safety Issue: | |
Description: | Incidence subjects eligible to proceeding to hematopoietic cell transplantation. Eligibility is defined by having a remission status as defined in the primary outcome. |
Measure: | aGvHD |
Time Frame: | Day 42 |
Safety Issue: | |
Description: | Incidence of acute graft versus host disease (aGvHD) |
Measure: | Overall survival at 12 months |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Incidence of overall survival |
Measure: | Overall survival at 24 months |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Incidence of overall survival |
Measure: | Disease free survival at 12 months |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Incidence of disease free survival |
Measure: | Disease free survival at 24 months |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Incidence of disease free survival |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Masonic Cancer Center, University of Minnesota |
Trial Keywords
Last Updated
April 26, 2019