Clinical trial NCT04679194: Study of Mana 312 (Multi Tumor-Associated Antigen T Cells) in Adults With AML/MDS After HSCT
Official title: Ph 1 Study of Escalating Single & Multiple Doses of Mana 312 (Multi Tumor-Associated Antigen T Cells) Administered to Adult Subjects With Acute Myeloid Leukemia or Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: AML/MDS
Keywords: AML
MDS
Relapse
HSCT
Lead sponsor: Mana Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-12-22
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, open-label, non-randomized, single and multiple dose escalation study designed to evaluate the safety and preliminary efficacy of administering Mana 312 to subjects with AML/MDS after allogeneic HSCT.

Detailed description: This is a Phase 1, open-label, non-randomized, single and multiple dose escalation study designed to evaluate the safety and preliminary efficacy (prevention of, or treatment of relapse) of administering Mana 312 to subjects with AML/MDS after allogeneic HSCT. The study will evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of single and multiple doses of Mana 312. Each cycle of administration of Mana 312 will be 28 days.

In the Escalation Cohorts, subjects with low, intermediate, and adverse/high risk of relapse will be enrolled using a modified 3+3 design. Upon completion of Cycle 1, subjects not experiencing dose-limiting toxicity (DLT) may continue receiving their assigned Mana 312 dose every 28 days for an additional 2 doses unless the subject experiences progressive disease (PD), exhausts their supply of Mana 312, experiences intolerable side effects, is removed by the Investigator, withdraws consent, or the study is terminated. After Cohort 1 has been completed (i.e., a decision has been made to proceed to Cohort 2), enrollment will be limited to subjects with high-risk of relapse AML/MDS (see Inclusion Criterion #4b) until the RP2D is determined).

In the Expansion Cohort, only subjects with high risk of relapse AML/MDS will be enrolled using the RP2D of Mana 312. Subjects in the Expansion Cohort will receive Mana 312 at the time of relapse or at 1 year after HSCT, whichever is first. Subjects not experiencing dose-limiting toxicity (DLT) may continue receiving their assigned Mana 312 dose every 28 days for an additional 2 doses unless the subject experiences progressive disease (PD), exhausts their supply of Mana 312, experiences intolerable side effects, or the study is terminated.

Eligibility criteria: Select Inclusion Criteria:

1. Subject is ≥18 years of age on the day Informed Consent is signed and dated.
2. Subject must have received only one allogeneic HSCT from a related or unrelated donor prior to administration of Mana 312.
3. Subject has a donor who has agreed to donate leukocytes for manufacture of Mana 312 and who is the same donor who provided cells for the subject's current HSCT.
4. a. Prior to HSCT, for Escalation Cohort 1, subject has AML/MDS b. Prior to HSCT, for Escalation Cohorts after Cohort 1 and for the Expansion Cohort, a subject must have high risk of relapse AML/MDS
5. Mana 312 product is available

   The following Inclusion Criteria apply only during the Pre-Infusion Screening Phase, prior to the time of the planned first infusion of Mana 312.
6. Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 or Karnofsky/Lansky score of ≥ 50.
7. Subjects in the Expansion Cohort must have a relapse of AML/MDS (MRD+ or morphologic relapse)
8. Subject has adequate organ function

Select Exclusion Criteria:

1. Subject has received antibody that affects T-cell number or function
2. Subject has received a donor lymphocyte infusion (DLI) for the current HSCT.
3. Evidence of GVHD ≥ Grade 2 in any organ system, or active bronchiolitis obliterans syndrome, sclerotic GVHD, or symptomatic serositis.
4. Subject has undergone major surgery (excluding minor procedures, eg, placement of vascular access, gastrointestinal/biliary stent, apheresis, or biopsy) \< 21 days prior to the first planned infusion of Mana 312.
5. Subject has an active and clinically relevant infection
6. Subject has symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression (radiation therapy to local site for disease control is allowed if ≥ 14 days prior to Screening and all AE from radiation therapy have resolved to ≤ Grade 1 prior to the planned first Mana 312 infusion).
7. Subject has any other medical condition not listed above or social condition that, in the opinion of the Investigator, might place the subject at increased risk, adversely affect compliance, or confound safety or other clinical study data interpretation.

Primary outcomes:
measure: Escalation Cohorts: Identify the Maximum Tolerated Dose (MTD) of Mana 312 based on the safety and tolerability of single and multiple doses.
timeFrame: 6 months
measure: Escalation Cohorts: Identify the Recommended Phase 2 Dose (RP2D) of Mana 312 based on the safety and tolerability of single and multiple doses.
timeFrame: 6 months
measure: Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by CR.
timeFrame: 1 year
measure: Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by PFS.
timeFrame: 1 year
Secondary outcomes:
measure: Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by CR.
timeFrame: 1 year
measure: Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by PFS.
timeFrame: 1 year
measure: Expansion Cohort: Confirm safety of the RP2D by measurement of TEAEs.
timeFrame: 6 months
Other outcomes:
measure: Characterize the pharmacokinetics (PK) by measurement of Mana 312 cell counts
timeFrame: 6 months
measure: Characterize the pharmacokinetics (PK) by measurement of antidrug antibodies (ADAs)
timeFrame: 6 months
measure: Characterize the anti-drug antibody (ADA) response to Mana 312.
timeFrame: 6 months
measure: Determine Area Under the Curve (AUC) Pharmacokinetics of Mana 312
timeFrame: 6 months
measure: Measure the Maximum Concentration Pharmacokinetics of Mana 312
timeFrame: 6 months
measure: Measure blast cell antigen expression pharmacodynamic markers of Mana 312
timeFrame: 1 year
measure: Assess potential cytokine induction pharmacodynamic markers of Mana 312
timeFrame: 1 year
measure: Measure cell expansion pharmacodynamic markers of Mana 312
timeFrame: 1 year
measure: Measure immune subset pharmacodynamic markers of Mana 312.
timeFrame: 1 year
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Atlanta
country: United States
facility: Northside Hospital - Atlanta
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Texas Transplant/St David's South Austin
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant/Methodist Hospital
state: Texas
Study officials:
affiliation: Mana Therapeutics Interim Chief Medical Officer
name: Lou Vaickus, MD
role: PRINCIPAL_INVESTIGATOR
References: