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.

• Sponsor: Fate Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01627314
• Collaborator: (none)
• Enrollment: 62
• Locations: 11
• Arms: 4
• Duration (Months): 58
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Biological: ProHema-CB; Biological: Untreated CB	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ProHema-CB with MAC Preparative Regimen ProHema-CB and Wash-Only CB Unit with myeloablative conditioning regimen (MAC)	Biological: ProHema-CB; Ex-vivo CXCR4 upregulated hematopoietic progenitor cells, cord blood
Experimental: ProHema-CB with RIC Preparative Regimen ProHema-CB and Wash-Only CB Unit with reduced intensity conditioning regimen (RIC)	Biological: ProHema-CB; Ex-vivo CXCR4 upregulated hematopoietic progenitor cells, cord blood
Placebo Comparator: Control Arm with MAC Preparative Regimen Two Wash-Only CB Units (Untreated CB) with myeloablative conditioning regimen	Biological: Untreated CB; Cord Blood
Placebo Comparator: Control Arm with RIC Preparative Regimen Two Wash-Only CB Units (Untreated CB) with reduced intensity conditioning regimen	Biological: Untreated CB; Cord Blood

Outcome Measures

Primary Outcome Measures

1. Rate of early neutrophil engraftment using Myeloablative Conditioning [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.

2. Rate of early neutrophil engraftment using Reduced Intensity Conditioning [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

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

2. 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.

1. 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).

2. 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.

1. Biphenotypic/undifferentiated leukemia in first or subsequent CR (same definition of CR as for ALL/AML).

2. 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.

3. 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.

1. 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.

2. Both cord blood units (CBUs) are qualified by Fate Therapeutics

3. Age 15 to 55 years (myeloablative regimen) or 15 to 65 years (reduced intensity regimen)

4. Body weight > 45 kg

5. Investigator selection of conditioning regimen (myeloablative or reduced intensity)

6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.

7. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Emory University-Winship Cancer Institute	Atlanta	Georgia	United States	30322
3	Loyola University Medical Center	Maywood	Illinois	United States	60153
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Boston Children's Hospital	Boston	Massachusetts	United States	02215
6	Dana-Farber Cancer Institute- Hematopoietic Stem Cell Transplant Program	Boston	Massachusetts	United States	02215
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	Mount Sinai Hospital	New York	New York	United States	10029
10	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
11	Oregon Health Sciences	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Fate Therapeutics

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fate Therapeutics
• ClinicalTrials.gov Identifier: NCT01627314
• Other Study ID Numbers: FT1050-03
• First Posted: Jun 25, 2012
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms

Study Results

No Results Posted as of Nov 30, 2021