Clinical Trials /

Study of Mana 312 (Multi Tumor-Associated Antigen T Cells) in Adults With AML/MDS After HSCT

NCT04679194

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: ManaTx-1001
  • NCT ID: NCT04679194

Conditions

  • AML/MDS

Interventions

DrugSynonymsArms
Mana 312Mana 312

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Mana 312ExperimentalMana 312 is administered intravenously (IV) within 30 minutes in either an inpatient or outpatient setting; either a central or peripheral IV line may be used. Each cycle of administration of Mana 312 will be 28 days. Subjects not experiencing dose-limiting toxicity (DLT) following their initial dose may continue receiving their assigned Mana 312 dose every 28 days for an additional 2 doses
  • Mana 312

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Escalation Cohorts: Identify the Maximum Tolerated Dose (MTD) of Mana 312 based on the safety and tolerability of single and multiple doses.
Time Frame:6 months
Safety Issue:
Description:Maximum Tolerated Dose

Secondary Outcome Measures

Measure:Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by CR.
Time Frame:1 year
Safety Issue:
Description:CR Rate
Measure:Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by PFS.
Time Frame:1 year
Safety Issue:
Description:PFS Rate
Measure:Expansion Cohort: Confirm safety of the RP2D by measurement of TEAEs.
Time Frame:6 months
Safety Issue:
Description:Assess number of Treatment Related Adverse Events

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mana Therapeutics

Trial Keywords

  • AML
  • MDS
  • Relapse
  • HSCT

Last Updated

December 24, 2020