The PUMA Trial is a Trial of a Single ProHema Modulated-Cord Blood (CB) Unit as Part of a Double CB Transplant in Patients With Hematologic Malignancies.

• ClinicalTrials.gov Identifier: NCT01627314
• Recruitment Status: Terminated
• First Posted: June 25, 2012
• Last Update Posted: November 30, 2021
• Sponsor: Fate Therapeutics
• Information provided by (Responsible Party): Fate Therapeutics

Tracking Information

• First Submitted Date: June 21, 2012
• First Posted Date: June 25, 2012
• Last Update Posted Date: November 30, 2021
• Study Start Date: July 2012
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 26, 2021)

• Rate of early neutrophil engraftment using Myeloablative Conditioning [ Time Frame: Neutrophil engraftment < 26 days ]
  To determine the rate of neutrophil engraftment after a single ProHema-CB unit is used as part of a double CB transplant following myeloablative conditioning for subjects with hematologic malignancies.
• Rate of early neutrophil engraftment using Reduced Intensity Conditioning [ Time Frame: Neutrophil engraftment < 21 days ]
  To determine the rate of neutrophil engraftment after a single ProHema-CB unit is used as part of a double CB transplant following reduced intensity conditioning for subjects with hematologic malignancies.

Original Primary Outcome Measures (submitted: June 22, 2012)

Neutrophil engraftment/chimerism [ Time Frame: Day 26 ]

To determine the rate of neutrophil engraftment by Day 26 after a single ProHema-CB unit is used as part of a double CB transplant following myeloablative conditioning for subjects age 15-55 years with hematologic malignancies.

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: June 22, 2012)

Neutrophil engraftment [ Time Frame: Day 42 ]

To define measures of engraftment, including time to neutrophil engraftment, cumulative incidence of neutrophil engraftment by Day 42, time to platelet engraftment (> 20K and > 50K), cumulative incidence of platelet engraftment by Day 180, and rates of primary and secondary graft failure

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The PUMA Trial is a Trial of a Single ProHema Modulated-Cord Blood (CB) Unit as Part of a Double CB Transplant in Patients With Hematologic Malignancies.
• Official Title: A Phase 2 Controlled Trial of a Single ProHema®-CB Unit (Ex Vivo Modulated Human Cord Blood) As Part of a Double Umbilical Cord Blood Transplant Following Myeloablative or Reduced Intensity Conditioning For Patients Age 15-65 Years With Hematologic Malignancies.
• Brief Summary: This study is an open-label randomized, prospectively and historically controlled trial of the safety and efficacy of a single ProHema-CB unit used as part of a double CB transplant following myeloablative or reduced intensity conditioning for subjects age 15-65 years with hematologic malignancies. A maximum of 60 eligible subjects will be enrolled and treated in the trial at approximately 10 centers within the U.S.
• Detailed Description: All subjects will receive a myeloablative or reduced intensity conditioning regimen, after which they will receive 2 Human Leukocyte Antigen (HLA)-matched or partially matched umbilical cord blood (UCB) units. A total of 40 subjects will receive one ProHema-CB as part of a double CB transplant and an additional 20 subjects will be enrolled as concurrent controls. The determination of which CB unit will be the ProHema-CB unit will be made based primarily upon the degree of HLA match.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hematologic Malignancies

Intervention

• Biological: ProHema-CB
  Ex-vivo CXCR4 upregulated hematopoietic progenitor cells, cord blood
• Biological: Untreated CB
  Cord Blood

Study Arms

• Experimental: ProHema-CB with MAC Preparative Regimen
  ProHema-CB and Wash-Only CB Unit with myeloablative conditioning regimen (MAC)
  Intervention: Biological: ProHema-CB
• Experimental: ProHema-CB with RIC Preparative Regimen
  ProHema-CB and Wash-Only CB Unit with reduced intensity conditioning regimen (RIC)
  Intervention: Biological: ProHema-CB
• Placebo Comparator: Control Arm with MAC Preparative Regimen
  Two Wash-Only CB Units (Untreated CB) with myeloablative conditioning regimen
  Intervention: Biological: Untreated CB
• Placebo Comparator: Control Arm with RIC Preparative Regimen
  Two Wash-Only CB Units (Untreated CB) with reduced intensity conditioning regimen
  Intervention: Biological: Untreated CB

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 26, 2021): 62
• Original Estimated Enrollment (submitted: June 22, 2012): 45
• Actual Study Completion Date: May 2017
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion:

1. Patients with hematologic malignancies for whom allogeneic stem cell transplantation is deemed clinically appropriate. Eligible diseases and stages include:

   1. Acute lymphoblastic leukemia (ALL) (including T lymphoblastic lymphoma) in complete remission (CR).

      • Remission is defined as < 5% blasts with no morphological characteristics of acute leukemia in a bone marrow with > 5% cellularity.

   2. Myelodysplastic disease, International Prognostic Scoring System (IPSS) Intermediate-2 or High risk (e.g., refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Patients have to have received leukemia type induction chemotherapy within ≤ 3 months and with ≤ 10% blasts by a bone marrow aspirate; a single hypomethylating agent is not considered adequate cytotoxic chemotherapy; all subtypes except chronic myelomonocytic leukemia (CMML).

   3. Acute myelogenous leukemia (AML) in high risk first CR or second or subsequent CR.

      • High risk first CR is defined by but is not limited to at least one of the following factors: greater than one cycle of induction chemotherapy to achieve CR, prior myelodysplastic syndrome (MDS), presence of fms-like tyrosine kinase 3 (FLT3) abnormalities, French-American-British (FAB) M6 or M7 subtypes of leukemia, or adverse cytogenetics.
      • Remission is defined as < 5% blasts with no morphological characteristics of acute leukemia (e.g. Auer Rods) in a bone marrow with > 5% cellularity.
      • AML arising from myelofibrosis is not permitted.
   4. Biphenotypic/undifferentiated leukemia in first or subsequent CR (same definition of CR as for ALL/AML).
   5. Chronic myelogenous leukemia (CML) with prior exposure to cytotoxic chemotherapy for the treatment of blast phase or with demonstrated intolerance to at least 2 tyrosine kinase inhibitors.

   6. Non Hodgkin's lymphoma (T cell, large cell or mantle cell) or Hodgkin's lymphoma in second or subsequent CR or in partial remission (PR) with documented chemosensitivity. In addition, marginal zone lymphoma or follicular lymphoma that has progressed after ≥ 2 therapies (excluding single agent rituximab).

      • If the myeloablative conditioning regimen is selected, a history of prior myeloablative procedure is not allowed.
      • If the reduced intensity conditioning regimen is selected, and the subject has had a prior autologous transplant, it must have taken place > 3 months from anticipated Day 0 visit.
2. Lack of suitable 5 6/6 HLA matched related or (if institutional guidelines dictate) suitable 8/8 HLA A, B, C, DRß1 matched unrelated donor; or unrelated donor not available within appropriate timeframe.
3. Both cord blood units (CBUs) are qualified by Fate Therapeutics
4. Age 15 to 55 years (myeloablative regimen) or 15 to 65 years (reduced intensity regimen)
5. Body weight > 45 kg
6. Investigator selection of conditioning regimen (myeloablative or reduced intensity)
7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
8. Signed Institutional Review Board (IRB) approved Informed Consent Form (ICF).

Exclusion:

1. History of prior allogeneic transplantation
2. Cardiac disease: symptomatic congestive heart failure or evidence of left ventricular dysfunction (Ejection fraction < 50%) as measured by gated radionuclide ventriculogram or echocardiogram; active angina pectoris, or uncontrolled hypertension; history of myocardial infarction with depressed ejection fraction.
3. Pulmonary disease: symptomatic chronic obstructive lung disease, symptomatic restrictive lung disease, or corrected diffusing capacity for carbon monoxide (DLCO) of < 50% of predicted, corrected for hemoglobin.
4. Renal disease: serum creatinine > 2.0 mg/dl and calculated creatinine clearance < 40 mL/min.
5. Hepatic disease: serum bilirubin > 2.0 mg/dl (except in the case of Gilbert's syndrome or ongoing hemolytic anemia), aspartate aminotransferase (SGOT) or alanine aminotransferase (SGPT) > 5 × upper limit of normal.
6. Neurologic disease: symptomatic leukoencephalopathy, active central nervous system (CNS) malignancy or other neuropsychiatric abnormalities believed to preclude transplantation.
7. HIV antibody.
8. Uncontrolled infection.
9. Pregnancy or breast feeding mother.
10. Inability to comply with the requirements for care after allogeneic stem cell transplantation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01627314
• Other Study ID Numbers: FT1050-03
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fate Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Fate Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chris Storgard, M.D.; Fate Therapeutics

• PRS Account: Fate Therapeutics
• Verification Date: November 2021