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.

Hematologic Malignancies Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01627314
• Other study ID #: FT1050-03
• Status: Terminated
• Phase: Phase 2
• Start date: July 2012
• Est. completion date: May 2017

Study information

• Verified date: November 2021
• Source: Fate Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 62
• Est. completion date: May 2017
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Malignancies
• Hematologic Neoplasms
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University-Winship Cancer Institute	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute- Hematopoietic Stem Cell Transplant Program	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Mount Sinai Hospital	New York	New York
United States	Oregon Health Sciences	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of early neutrophil engraftment using Myeloablative Conditioning	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.	Neutrophil engraftment < 26 days
Primary	Rate of early neutrophil engraftment using Reduced Intensity Conditioning	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.	Neutrophil engraftment < 21 days