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

NCT04679194 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ManaTx-1001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 8

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.

Conditions

AML/MDS

Keywords

AML; MDS; Relapse; HSCT

Outcome Measures

Primary Outcomes (4)

• Escalation Cohorts: Identify the Maximum Tolerated Dose (MTD) of Mana 312 based on the safety and tolerability of single and multiple doses.

  Maximum Tolerated Dose

  6 months

• Escalation Cohorts: Identify the Recommended Phase 2 Dose (RP2D) of Mana 312 based on the safety and tolerability of single and multiple doses.

  Recommended Phase 2 Dose

  6 months

• Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by CR.

  CR Rate

  1 year

• Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by PFS.

  PFS Rate

  1 year

Secondary Outcomes (3)

• Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by CR.

  1 year

• Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by PFS.

  1 year

• Expansion Cohort: Confirm safety of the RP2D by measurement of TEAEs.

  6 months

Other Outcomes (9)

• Characterize the pharmacokinetics (PK) by measurement of Mana 312 cell counts

  6 months

• Characterize the pharmacokinetics (PK) by measurement of antidrug antibodies (ADAs)

  6 months

• Characterize the anti-drug antibody (ADA) response to Mana 312.

  6 months

Study Arms (1)

Mana 312

EXPERIMENTAL

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

Interventions

Mana 312 BIOLOGICAL

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).

Mana 312

Eligibility Criteria

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

You may qualify if:

• Subject is ≥18 years of age on the day Informed Consent is signed and dated.
• Subject must have received only one allogeneic HSCT from a related or unrelated donor prior to administration of Mana 312.
• 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.
• 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
• Mana 312 product is available
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 or Karnofsky/Lansky score of ≥ 50.
• Subjects in the Expansion Cohort must have a relapse of AML/MDS (MRD+ or morphologic relapse)
• Subject has adequate organ function

You may not qualify if:

• Subject has received antibody that affects T-cell number or function
• Subject has received a donor lymphocyte infusion (DLI) for the current HSCT.
• Evidence of GVHD ≥ Grade 2 in any organ system, or active bronchiolitis obliterans syndrome, sclerotic GVHD, or symptomatic serositis.
• 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.
• Subject has an active and clinically relevant infection
• 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).
• 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.

Sponsors & Collaborators

• Mana Therapeutics: lead

Study Sites (8)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Northside Hospital - Atlanta

Atlanta, Georgia, 30309, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66103, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Texas Transplant/St David's South Austin

Austin, Texas, 78704, United States

Location

Texas Transplant/Methodist Hospital

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lou Vaickus, MD

  Mana Therapeutics Interim Chief Medical Officer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: December 22, 2020
• Study Start: December 8, 2020
• Primary Completion: March 28, 2023
• Study Completion: March 28, 2023
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)