CMLPhase 1UCBNCT00891592
Umbilical Cord Blood Transplant for Hematological Malignancies
A Phase 1 study testing Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells and Observation Arm in people with CML and AML, run by University of Pennsylvania at 1 site in United States.
Trial summary
This protocol will enroll subjects with advanced hematologic malignancies who do not have a suitable related or unrelated donor to undergo a Stem Cell Transplant. In this study, subjects will undergo a Stem Cell Transplant using Cord Blood. Read more about this study
- Who is it for?
- Ages 21 to 50 years
- What is being tested?
- Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells and Observation Arm
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Relapsed or persistent advanced hematologic malignancy; incurable with standard chemotherapy and eligible for allogeneic HSCT, including:
- CHRONIC MYELOGENOUS LEUKEMIA (CML). Subjects in accelerated or blast phase or subjects in chronic phase with inadequate response to Imatinib or intolerant to Imatinib.
- ACUTE MYELOGENOUS LEUKEMIA (AML). Subject with high risk disease in first complete remission (CR). High risk disease includes the following cytogenetic abnormalities: monosomy 7, deletion 5, trisomy 8, inversion 3, t(3;3), t(6;9), or t(6;11). Subjects with complex cytogenetic abnormalities (more than 3 chromosomal abnormalities).
- ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects with diagnosis of AML after receiving chemotherapy, radiation therapy or biopsy showing myelodysplastic syndrome.
- ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects with persistent AML after 2 cycles of standard induction chemotherapy.
- ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects in first complete remission.
Show all 18Show fewer
- MYELODYSPLASTIC SYNDROME (MDS). Subjects with intermediate or high risk disease based upon International Prognostic Scoring System.
- ACUTE LYMPHOBLASTIC LEUKEMIA (ALL). Subjects with Philadelphia Chromosome (have t(9;22) cytogenetic abnormality) or molecular documentation for BCR-ABL translocation.
- ACUTE LYMPHOBLASTIC LEUKEMIA (ALL). Subjects with primary refractory disease or subjects in 1st complete remission.
- NHL or HODKIN'S DISEASE. Subjects who relapse following autologous Stem Cell Transplant.
- INDOLENT NHL. Subjects with progressive disease following > 2 regimens.
- MULTIPLE MYELOMA. Subjects who relapse following following autologous Stem Cell Transplant.
- Adults age 21-50.
- Expected survival 4 weeks.
- Subjects with no suitable related or unrelated donor for Stem Cell Transplant.
- Subject has suitable Umbilical Cord Blood (UCB) unit available.
- Subject has: Ejection fraction > 45%; DLCO.45% predicted; Creatinine < 2; Total bilirubin < 2X normal; Transaminases < 2X normal.
- Subject is capable of giving informed consent.
Who cannot join
- Subject is pregnant or lactating.
- Subject has an uncontrolled infection.
- Subject has an active or untreated disease involving the central nervous system.
- Subject has an active or uncontrolled medical condition that would preclude participation in the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase 1 Dose Escalation Study of Infusion of ex Vivo cd3/cd28 Costimulated Umbilical Cord Blood-derived t Cells in Adults Undergoing Transplantation for Advanced Hematologic Malignancies
This protocol will enroll subjects with advanced hematologic malignancies who do not have a suitable related or unrelated donor to undergo a Stem Cell Transplant.
In this study, subjects will undergo a Stem Cell Transplant using Cord Blood. Part of the cord blood will be used for the Stem Cell Transplant and part of the cord blood will be sent to a laboratory in order to grow the T cells (from the cord blood) and increase the activity of the cord blood T cells.
The purpose of this part of the study is to see if it is safe to give study subjects activated T cells made from a small portion of their donor UCB unit immediately after the UCB transplant. Activated T cells have been used safely in stem cell transplantation studies in the past, but they have never been studied UCB transplantation.
Read the detailed description
The main study intervention includes CD3/CD28 ex vivo costimulated T cells derived from a thawed umbilical cord blood unit, co-infused following a myeloablative conditioning regimen.
Activated T cells are T cells that have been activated in the laboratory by exposure to 2 compounds or molecules called CD3 and CD28; when T cells are exposed to both of these compounds at the same time, they become activated or "stimulated" and may be more effective in fighting infections, cancer cells, and promoting the recovery of red cells, white cells, and platelets after transplantation. At the Hospital of the University of Pennsylvania, activated T cells are prepared at the Clinical Cell and Vaccine Production Facility, also known as the CVPF.
- Being tested
- Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells, Observation Arm
- Keywords
- AML, MDS, ALL, NHL, Multiple Myeloma, Hodgkin's
- Medical subject headings
- Multiple Myeloma, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cellsBiological
Single infusion of Cord Blood Cells AND Single Infusion of ex vivo CD3/CD28 costimulated Umbilical Cord Blood T cells.
Table 6: Dose escalation (Dose level CD3+ cell dose)
- 1xE5 cells/kg
- 2xE6 cells/kg
- 3xE7 cells/kg
- 4xE8 cells/kg
Observation ArmOther
Single infusion of Cord Blood Cells
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Arm | Experimental | Subjects with cord blood stored in more than one fraction will be enrolled into Dose Escalation Arm. Subjects will receive Cord Blood Stem Cell Transplant followed by expanded Cord Blood T cells on Day 0. Receives: Biological: Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells |
| Observation Arm | Active comparator | Subjects with cord blood stored in one fraction will be enrolled into the Observation Arm. Subjects will receive Cord Blood Stem Cell Transplant on Day 0. Receives: Other: Observation Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion.
Measured: 90 Days post Transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2009 (estimated)
- Study startJan 2009
- Primary completionNov 2011
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CMLStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Porter, MD, Principal investigator, University of PennsylvaniaElizabeth Hexner, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00891592
- Sponsor's protocol ID
- UPCC 02707
- Acronym
- UCB
- Status last verified
- Aug 2016
- First submitted
- 29 Apr 2009
- Last updated
- 19 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Hexner EO, Luger SM, Reshef R, Jeschke GR, Mangan JK, Frey NV, Frank DM, Richman LP, Vonderheide RH, Aqui NA, Rosenbach M, Zhang Y, Chew A, Loren AW, Stadtmauer EA, Levine BL, June CH, Emerson SG, Porter DL. Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment. Am J Hematol. 2016 May;91(5):453-60. doi: 10.1002/ajh.24303. Epub 2016 Apr 4.
PubMed 26858124
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study of Infusion of ex Vivo cd3/cd28 Costimulated Umbilical Cord Blood-derived t Cells in Adults Undergoing Transplantation for Advanced Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00891592
- Acronym / sponsor ID
- UCB / UPCC 02707
- Keywords
- AML, MDS, ALL, NHL, Multiple Myeloma, Hodgkin's
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Nov 2011 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 1 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This protocol will enroll subjects with advanced hematologic malignancies who do not have a suitable related or unrelated donor to undergo a Stem Cell Transplant.
In this study, subjects will undergo a Stem Cell Transplant using Cord Blood. Part of the cord blood will be used for the Stem Cell Transplant and part of the cord blood will be sent to a laboratory in order to grow the T cells (from the cord blood) and increase the activity of the cord blood T cells.
The purpose of this part of the study is to see if it is safe to give study subjects activated T cells made from a small portion of their donor UCB unit immediately after the UCB transplant. Activated T cells have been used safely in stem cell transplantation studies in the past, but they have never been studied UCB transplantation.
Detailed description
The main study intervention includes CD3/CD28 ex vivo costimulated T cells derived from a thawed umbilical cord blood unit, co-infused following a myeloablative conditioning regimen.
Activated T cells are T cells that have been activated in the laboratory by exposure to 2 compounds or molecules called CD3 and CD28; when T cells are exposed to both of these compounds at the same time, they become activated or "stimulated" and may be more effective in fighting infections, cancer cells, and promoting the recovery of red cells, white cells, and platelets after transplantation. At the Hospital of the University of Pennsylvania, activated T cells are prepared at the Clinical Cell and Vaccine Production Facility, also known as the CVPF.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Arm | Experimental | Biological: Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cellsSubjects with cord blood stored in more than one fraction will be enrolled into Dose Escalation Arm. Subjects will receive Cord Blood Stem Cell Transplant followed by expanded Cord Blood T cells on Day 0. |
| Observation Arm | Active comparator | Other: Observation ArmSubjects with cord blood stored in one fraction will be enrolled into the Observation Arm. Subjects will receive Cord Blood Stem Cell Transplant on Day 0. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Relapsed or persistent advanced hematologic malignancy; incurable with standard chemotherapy and eligible for allogeneic HSCT, including:
- CHRONIC MYELOGENOUS LEUKEMIA (CML). Subjects in accelerated or blast phase or subjects in chronic phase with inadequate response to Imatinib or intolerant to Imatinib.
- ACUTE MYELOGENOUS LEUKEMIA (AML). Subject with high risk disease in first complete remission (CR). High risk disease includes the following cytogenetic abnormalities: monosomy 7, deletion 5, trisomy 8, inversion 3, t(3;3), t(6;9), or t(6;11). Subjects with complex cytogenetic abnormalities (more than 3 chromosomal abnormalities).
- ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects with diagnosis of AML after receiving chemotherapy, radiation therapy or biopsy showing myelodysplastic syndrome.
- ACUTE MYELOGENOUS LEUKEMIA (AML). Subjects with persistent AML after 2 cycles of standard induction chemotherapy.
Key exclusion criteria (4 listed)
- Subject is pregnant or lactating.
- Subject has an uncontrolled infection.
- Subject has an active or untreated disease involving the central nervous system.
- Subject has an active or uncontrolled medical condition that would preclude participation in the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cellsSingle infusion of Cord Blood Cells AND Single Infusion of ex vivo CD3/CD28 costimulated Umbilical Cord Blood T cells. Table 6: Dose escalation (Dose level CD3+ cell dose) * 1xE5 cells/kg * 2xE6 cells/kg * 3xE7 cells/kg * 4xE8 cells/kg | Biological | Dose Escalation Arm |
| Observation ArmSingle infusion of Cord Blood Cells | Other | Observation Arm |
Primary outcome
Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion.
Time frame: 90 Days post Transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2016.
- Derived from this study: PubMed 26858124Hexner EO, Luger SM, Reshef R, Jeschke GR, Mangan JK, Frey NV, Frank DM, Richman LP, Vonderheide RH, Aqui NA, Rosenbach M, Zhang Y, Chew A, Loren AW, Stadtmauer EA, Levine BL, June CH, Emerson SG, Porter DL. Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment. Am J Hematol. 2016 May;91(5):453-60. doi: 10.1002/ajh.24303. Epub 2016 Apr 4.
- Abramson Cancer Center Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Porter, MD principal investigator
University of Pennsylvania
Elizabeth Hexner, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ex Vivo CD3/CD28 costimulated Umbilical Cord Blood T cells and Observation Arm in people with CML and AML, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) is defined as grade 4 acute GVHD within the first 90 days following infusion. (time frame: 90 Days post Transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00891592, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2016.