Ph2 NK Cell Enriched DCIs w/wo RLR9 Agonist, DUK-CPG-001 From Donors Following Allogeneic SCT

NCT02452697 | Unknown Phase 2 Results DMC

• 2 other identifiers: Pro00057501IND 16610
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, parallel phase II study to evaluate the rates of progression-free survival and unacceptable toxicity in patients receiving NK cell-enriched donor lymphocyte infusions (DLIs) when administered alone or administered with the TLR9 agonist, DUK-CPG-001, from a 7-8/8 HLA-matched related or unrelated donor (Cohort A) or 4-6/8 HLA-matched related donor (Cohort B) following reduced intensity or non-ablative allogeneic stem cell transplantation. Randomization will be stratified for disease types (myeloid versus lymphoid malignancies). Primary endpoints are analyzed separately in Cohort A and B. Cohort A: 7-8/8 HLA-matched related or unrelated donor ("NK cell enriched-DLI only" arm or "NK cell enriched-DLI + DUK-CPG-001" arm) Cohort B: 4-6/8 HLA-matched related donor ("NK cell enriched-DLI only" arm or "NK cell enriched-DLI + DUK-CPG-001" arm)

Conditions

Myeloid Malignancies; Lymphoid Malignancies

Keywords

Nonmyeloablative; Stem Cell; Transplant

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) Rate

  To evaluate the one-year progression-free survival rate in patients receiving NK cell-enriched DLI administered alone from a 7-8/8 HLA-matched related or unrelated donor or 4-6/8 HLA-matched related donor following reduced intensity or non-ablative allogeneic stem cell transplantation and to evaluate the one-year progression-free survival rate in patients receiving NK cell-enriched DLI administered with a Toll-like receptor 9 (TLR9) ligand, DUK-CPG-001, from a 7-8/8 HLA-matched related or unrelated donor or 4-6/8 HLA-matched related donor following reduced intensity or non-ablative allogeneic stem cell transplantation

  Up to 1 year

• Number of Participants With Unacceptable Toxicity

  Unacceptable toxicity is defined as any of the following related to the DLI procedure: 1. Grade \> III aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting \> 7 days; 2. Grade 4 toxicity from the procedure in the cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic categories that lasts \> 5 days; 3. Treatment-related death caused by the toxicities related to DLI procedure.

  Up to 100 days

Secondary Outcomes (5)

• Recovery of Immune Cell Populations Pre and Post-Infusion

  Up to 100 days

• Immune Function Pre and Post-Infusion With Antigen Specific Recovery, as Measured by Elispot Assay

  Up to 100 days

• Immune Function Pre and Post-Infusion With Antigen Specific Recovery, as Measured by Immunoscope Assay

  Up to 100 days

• Immune Function Pre and Post-Infusion With Antigen Specific Recovery, as Measured by Flow-cytometric Cytokine Assay

  Up to 100 days

• Immune Function Pre and Post-Infusion With Antigen Specific Recovery, as Measured by Functional NK Lysis Assay

  Up to 100 days

Study Arms (4)

Cohort A - NK cell enriched-DLI only

ACTIVE COMPARATOR

Patients with a 7-8/8 human leukocyte antigen (HLA)-matched related or unrelated donor receiving natural killer (NK) cell enriched donor lymphocyte infusion (DLI) only

Biological: NK Cell enriched-DLI only

Cohort A - NK-DLI + DUK-CPG-001

EXPERIMENTAL

Patients with a 7-8/8 human leukocyte antigen (HLA)-matched related or unrelated donor receiving natural killer (NK) cell enriched donor lymphocyte infusion (DLI) and investigational DUK-CPG-001

Biological: NK-DLI + DUK-CPG-001

Cohort B - NK cell enriched-DLI only

ACTIVE COMPARATOR

Patients with a 4-6/8 human leukocyte antigen (HLA)-matched related donor receiving natural killer (NK) cell enriched donor lymphocyte infusion (DLI) only

Biological: NK Cell enriched-DLI only

Cohort B - NK-DLI + DUK-CPG-001

EXPERIMENTAL

Patients with a 4-6/8 human leukocyte antigen (HLA)-matched related donor receiving natural killer (NK) cell enriched donor lymphocyte infusion (DLI) and investigational DUK-CPG-001

Biological: NK-DLI + DUK-CPG-001

Interventions

NK Cell enriched-DLI only BIOLOGICAL

The first NK cell-enriched DLI will be administered one to six months post transplant. The second NK cell-enriched DLI will be administered one to three months post the first infusion, in patients who have ≤ grade II aGVHD at the time of infusion and have not had unacceptable toxicities from the first infusion. Patients will continue on their stable dose of immunosuppressive agents started for therapy of acute GVHD before the NK cell-enriched DLI, and will not taper until at least 6 weeks following the each NK cell-enriched DLI (unless disease progression or patient toxicity from the agents requires earlier taper). The donor NK cells will be infused over 30 minutes intravenously. If signs of GVHD occur after NK cell-enriched DLI, immunosuppressive agents may be started.

Cohort A - NK cell enriched-DLI only; Cohort B - NK cell enriched-DLI only

NK-DLI + DUK-CPG-001 BIOLOGICAL

DUK-CPG-001 was synthesized by Agilent Technologies (Boulder, CO) in 2013. Bulk DUK-CPG-001 has been resuspended in normal saline with a final concentration of 10 mg/mL, aliquoted into 0.75 mL (7.5 mg) per tube and stored at -20oC in the Investigational Chemotherapy Service pharmacy at Duke. DUK-CPG-001 will be thawed at room temperature right before use and injected intravenously right after NK cell-enriched DLI. The drug will be used within 4 hours of thawing. On the day of NK cell-enriched DLI, for those patients who are randomized to receive DUK-CPG-001, 0.5 mL (5 mg) aliquots of DUK-CPG-001 will be dispensed to nurse. It will be thawed at room temperature right before use and injected intravenously right after NK cell-enriched DLI.

Cohort A - NK-DLI + DUK-CPG-001; Cohort B - NK-DLI + DUK-CPG-001

Eligibility Criteria

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

You may qualify if:

• Patients with hematologic diseases who have undergone T-cell depleted reduced intensity or non-ablative allogeneic transplantation, using a 7-8/8 HLA-matched related or unrelated donor or 4-6/8 HLA-matched related donor. This may include patients with a mixed chimeric state or disease persistence or at high risk of relapse.
• Performance status must be ECOG PS 0, 1, or 2.
• Donor cellular engraftment of at least 2.5% from the non-myeloablative procedure.
• \< Grade 2 acute GVHD at time of the first NK cell-enriched DLI. Patients with treated acute GVHD must be on a stable dose of therapy (no increase in immunosuppressive therapy for the 2 weeks before planned NK cell-enriched DLIs). The dosage/level of immunosuppressive therapy at the time of NK-DLIs should be no greater than 20 mg of prednisone daily or mycophenolate 500 mg bid daily or cyclosporine with a target level of 200 ng/mL or tacrolimus with a target level of 10 ng/mL.
• Estimated survival of at least 8 weeks.
• Age of \>= 18 years.
• Females of childbearing potential should have a negative serum beta-HCG test within 48 hours of beginning DLI and/or DUK-CPG-01 unless contraception is used after initial testing. A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Males must agree to use a medically acceptable form of birth control in order to be in this study and for 3 months after infusion

You may not qualify if:

• Pregnant or lactating women.
• Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol.
• Patients likely to have a significantly better durable response to allogeneic transplant alone (better than 60% progression free longer than 2 years) includes: those with myeloproliferative diseases or hemoglobinopathies with over 50% T cell subset engraftment (assessed around 100 days post transplant); It is not anticipated that any such patients would be transplanted within our program, however but those in first remission AML patients with good risk standard genetics or normal genetics with either NPM1 or CEBPA mutations, first chronic phase CML without kinase gene mutations, follicular lymphoma patients in first remission who only required 1 regimen to attain remission all would be excluded from this protocol.
• Adult donors must be an HLA 4-8/8 match with the patient and must be capable of providing informed consent.
• Potential donors under the age of 18 must have a 'single patient exemption' approved by the IRB. The donor must provide assent and the donor's parent or guardian must provide permission for minor participation. Donors under the age of 18 who cannot assent based on their developmental stage will not be included.
• Donor must not have any medical condition which would make apheresis more than a minimal risk, and should have the following:
• Family members will be considered for donation if they do not have a history of known cardiac problem and do not have abnormal cardiac findings by physical examination. Those with a history of cardiac problems or abnormal cardiac findings by physical examination should undergo a stress evaluation or be evaluated by a cardiologist and deemed eligible to donate.
• Documented bilirubin and hepatic transaminases of \< 2.5 x ULN,
• Documented adequate hematologic parameters including a hematocrit \> 35% for males and 33% for females, white blood cell count of \>=3,000, and platelets \>=80,000.
• FACT labs and final test results available prior to infusion into the patient. In the second donation from the donor, the FACT labs must be redrawn within 30 days of initiation of apheresis. Positive serologies are not repeated as they remain positive for lifetime.
• Females of childbearing potential should have a negative serum beta-HCG test within 1 week of beginning apheresis. A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). A tubal ligation is adequate documentation that a patient is not of child bearing potential.
• /8 HLA matched unrelated donors will be matched at least as HLA -A, -B, C and -DRB1. Criterion for donation will be those allowing donation following the NMDP accepted donor criterion and program SOPs for the typical matched unrelated donors.

Sponsors & Collaborators

• Cristina Gasparetto: lead
• Agilent Technologies, Inc.: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Results Point of Contact

• Title: Cristina Gasparetto, MD
• Organization: Duke University

cristina.gasparetto@duke.edu

919-668-1000

Study Officials

• Cristina Gasparetto, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 6, 2015
• First Posted: May 25, 2015
• Study Start: June 8, 2016
• Primary Completion: July 23, 2022
• Study Completion: October 1, 2024
• Last Updated: February 20, 2024
• Results First Posted: February 20, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)