Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04679194
Recruitment Status : Recruiting
First Posted : December 22, 2020
Last Update Posted : August 26, 2021
Sponsor:
Information provided by (Responsible Party):
Mana Therapeutics

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.

Condition or disease Intervention/treatment Phase
AML/MDS Biological: Mana 312 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 8, 2020
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Mana 312

Mana 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

Biological: Mana 312

Mana 312 is a cellular product comprised of expanded T cells derived from allogeneic donor leukocytes that have been stimulated with monocyte derived dendritic cells pulsed with tumor-associated antigen (TAA) peptide mixes for 3 antigens: Wilms Tumor gene 1 (WT 1), the preferentially expressed antigen of melanoma (PRAME), and Survivin.

Each Mana 312 product is specifically matched for an individual subject and will be manufactured from leukocytes from the same donor who provided stem cells to that subject for their current allogeneic hematopoietic stem cell transplantation (HSCT).





Primary Outcome Measures :
  1. 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 ]
    Maximum Tolerated Dose

  2. Escalation Cohorts: Identify the Recommended Phase 2 Dose (RP2D) of Mana 312 based on the safety and tolerability of single and multiple doses. [ Time Frame: 6 months ]
    Recommended Phase 2 Dose

  3. Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by CR. [ Time Frame: 1 year ]
    CR Rate

  4. Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by PFS. [ Time Frame: 1 year ]
    PFS Rate


Secondary Outcome Measures :
  1. Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by CR. [ Time Frame: 1 year ]
    CR Rate

  2. Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by PFS. [ Time Frame: 1 year ]
    PFS Rate

  3. Expansion Cohort: Confirm safety of the RP2D by measurement of TEAEs. [ Time Frame: 6 months ]
    Assess number of Treatment Related Adverse Events


Other Outcome Measures:
  1. Characterize the pharmacokinetics (PK) by measurement of Mana 312 cell counts [ Time Frame: 6 months ]
    Determine Mana 312 cell counts

  2. Characterize the pharmacokinetics (PK) by measurement of antidrug antibodies (ADAs) [ Time Frame: 6 months ]
    Measure presence or absence of antidrug antibodies to Mana 312

  3. Characterize the anti-drug antibody (ADA) response to Mana 312. [ Time Frame: 6 months ]
    Detect presence or absence of neutralizing antibodies to Mana 312

  4. Determine Area Under the Curve (AUC) Pharmacokinetics of Mana 312 [ Time Frame: 6 months ]
    AUC

  5. Measure the Maximum Concentration Pharmacokinetics of Mana 312 [ Time Frame: 6 months ]
    Cmax

  6. Measure blast cell antigen expression pharmacodynamic markers of Mana 312 [ Time Frame: 1 year ]
    Measure expression of three target antigens

  7. Assess potential cytokine induction pharmacodynamic markers of Mana 312 [ Time Frame: 1 year ]
    Assess potential cytokine induction as potential biomarker of pharmacodynamic activity

  8. Measure cell expansion pharmacodynamic markers of Mana 312 [ Time Frame: 1 year ]
    Measure cell expansion persistence of Mana 312 subclones

  9. Measure immune subset pharmacodynamic markers of Mana 312. [ Time Frame: 1 year ]
    Measure immune subset changes by flow cytometry



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04679194


Contacts
Layout table for location contacts
Contact: Barb Geiger, BSN, RN 9132062798 bgeiger@manatherapeutics.com
Contact: Karen Bowen, RN, BS 8593964655 karen.bowen@catalystcr.com

Locations
Layout table for location information
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Principal Investigator: Alireza Eghtedar, MD         
United States, Georgia
Northside Hospital - Atlanta Recruiting
Atlanta, Georgia, United States, 30309
Principal Investigator: Melhem Solh, MD         
United States, Kansas
University of Kansas Cancer Center Recruiting
Kansas City, Kansas, United States, 66103
Principal Investigator: Haitham Abdelhakim, MD         
Sub-Investigator: Joseph McGuirk, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: Roni Tamari, MD         
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Jeremy Pantin, MD         
Vanderbilt - Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Michael Byrne, MD         
United States, Texas
Texas Transplant/St David's South Austin Recruiting
Austin, Texas, United States, 78704
Principal Investigator: Aravind Ramakrishnan, MD         
Texas Transplant/Methodist Hospital Recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Behyar Zoghi, MD         
Sponsors and Collaborators
Mana Therapeutics
Investigators
Layout table for investigator information
Principal Investigator: Lou Vaickus, MD Mana Therapeutics Interim Chief Medical Officer
Layout table for additonal information
Responsible Party: Mana Therapeutics
ClinicalTrials.gov Identifier: NCT04679194    
Other Study ID Numbers: ManaTx-1001
First Posted: December 22, 2020    Key Record Dates
Last Update Posted: August 26, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mana Therapeutics:
AML
MDS
Relapse
HSCT