Haplo-identical Natural Killer (NK) Cells to Prevent Post-Transplant Relapse in AML and MDS (NK-REALM)

NCT04395092 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: BMT CTN 1803U24HL138660
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a Phase II, single arm, open label multicenter trial designed to investigate the use of haploidentical donor derived NK cells (K-NK002) for the treatment of patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who are undergoing haploidentical donor bone marrow transplantation (HaploBMT). K-NK002 is a NK cell product derived from peripheral blood leukocytes collected from a related donor (HLA-haploidentical matched) and enriched for NK cells with depletion of CD3+ T-lymphocytes (T-cells) followed by enriched ex-vivo expansion and administered to the patient prior to and following BMT.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndromes (MDS)

Keywords

K-NK002; NK cell therapy; AML; MDS

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of relapse

  Cumulative incidence of relapse at 1 year

  1 year

Secondary Outcomes (12)

• Determine the safety and tolerability of K-NK002 through incidence of (Serious) Adverse Events.

  1-year post-transplant.

• Overall survival (OS).

  1-year post-transplant.

• Rate of Non-Relapse Mortality (NRM).

  1-year post-transplant.

• Relapse-free survival.

  1-year post-transplant.

• GVHD-free survival.

  1-year post-transplant.

Study Arms (1)

K-NK002

EXPERIMENTAL

Biological: K-NK002; Procedure: Conditioning Regimen; Procedure: HaploBMT

Interventions

K-NK002 BIOLOGICAL

K-NK002 will be administered intravenous (IV) on Day -2, Day +7 and Day +28. Part One (Safety run-in): An initial safety run-in to confirm the starting dose, and safety and tolerability of K-NK002; * Dose cohort 1 will include 3 patients who will receive a dose of K-NK002 at 1 x 10E7 NK cells per kg. * Dose cohort 2 will include 3 patients who will receive K-NK002 at 1 x 10E8 NK cells per kg. Part Two (Open Enrollment): Enrollment into the second part of the study (Open Enrollment) can begin following Part One, confirmation of dose and safety.

K-NK002

Conditioning Regimen PROCEDURE

From Day -7 to Day -3: * Melphalan: 140 mg/m2 (100mg/m2 in patients ≥ 60) on Day -7. * Fludarabine: 40 mg/m2 daily for 4 doses starting on days -7. * TBI: 2 Gy on Day -3.

K-NK002

HaploBMT PROCEDURE

Bone marrow is the only allowed graft source for patients enrolled in this clinical trial

K-NK002

Eligibility Criteria

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

You may qualify if:

• Age 18 to 65 years.
• Weight at least 45 kg.
• Patients with AML must have high risk for disease relapse AND be in complete remission (CR), complete remission with incomplete hematologic recovery (CRi) or morphologic leukemia free state (MLFS). Patients with FLT3 internal tandem duplication (FLT3/ITD) mutation are eligible but must be made aware of alternative treatments available, e.g. tyrosine kinase inhibitor therapy as maintenance following transplantation.
• AML patients must be in CR, CRi or a MLFS, as defined by ELN 2017.
• Patients with high-risk MDS must meet one of the following criteria:
• i. De novo MDS with intermediate/high/very high Revised International Prognostic Scoring System (R-IPSS) risk scores with
• Bone marrow blasts \< 10%, AND
• Patients may be treatment-naïve, or have received prior treatment with hypomethylating agents or other therapies.
• ii. Secondary/therapy-related MDS with bone marrow blasts \< 10%.
• Cardiac function: LVEF ≥ 45%.
• Pulmonary function: DLCO corrected for hemoglobin ≥ 60% and FEV1 ≥ to 60% the predicted value.
• Serum creatinine \< 1.5 mg/dL or creatinine clearance by Cockroft-Gault ≥ to 50 ml/min
• Hepatic ALT/AST \< 5 x the institutional upper limit of normal (ULN) and total bilirubin \< 1.5 mg/dl with conjugated (direct) bilirubin \< 2 x ULN.
• a. Indirect hyperbilirubinemia due to Gilbert's syndrome is allowed including total bilirubin ≥ to 1.5 mg/dl
• Karnofsky Performance Score ≥ to 70%.

You may not qualify if:

• Prior allogeneic transplant.
• AML beyond CR2.
• Patients who have a suitable HLA-matched related donor.
• Donor specific anti-HLA antibodies (DSA) greater than 1000 MFI.
• Hepatitis B, Hepatitis C, or HIV positive by PCR.
• Liver cirrhosis or portal hypertension (successfully treated for Hepatitis B or C are recommended to be evaluated by elastography or liver biopsy to evaluated for cirrhosis).
• Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
• Another cancer in remission less than 2 yrs are not eligible. A history of a previously treated solid tumor whose remission status is 2 yrs or greater and are not receiving tumor directed therapy will be considered eligible. Hormonal therapy as a part of long-term maintenance post-malignancy is allowed.
• Concurrent participation in another investigational clinical trial(s) with interventions which could influence relapse, GVHD, or viral reactivation.
• Systemic corticosteroid use at the time of screening. Treatment with hydrocortisone for prevention of transfusion reactions are eligible, but use of methylprednisolone is not allowed.
• Woman who are pregnant or lactating.
• Any serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Sponsors & Collaborators

• Kiadis Pharma: lead
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northside Hospital

Atlanta, Georgia, 30432GA, United States

Location

MD Anderson

Houston, Texas, 77030TX, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Transplantation Conditioning

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Sumithira Vasu, MD

  Ohio State University

  STUDY CHAIR

• Richard Champlin, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 20, 2020
• Study Start: November 13, 2020
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2023
• Last Updated: June 22, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)