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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
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).
Colorado Blood Cancer Institute
Denver, Colorado, United States
Northside Hospital - Atlanta
Atlanta, Georgia, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
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
Time frame: 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
Time frame: 6 months
Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by CR.
CR Rate
Time frame: 1 year
Expansion Cohort: Assess preliminary antitumor efficacy of Mana 312 by PFS.
PFS Rate
Time frame: 1 year
Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by CR.
CR Rate
Time frame: 1 year
Escalation Cohorts: Assess preliminary evidence of Mana 312 antitumor efficacy by PFS.
PFS Rate
Time frame: 1 year
Expansion Cohort: Confirm safety of the RP2D by measurement of TEAEs.
Assess number of Treatment Related Adverse Events
Time frame: 6 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Tennessee Oncology
Nashville, Tennessee, United States
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, United States
Texas Transplant/St David's South Austin
Austin, Texas, United States
Texas Transplant/Methodist Hospital
San Antonio, Texas, United States