Hematopoietic/Lymphoid CancerPhase 1NCT03126864
Study of Adoptive Cellular Therapy Using Autologous T Cells Transduced With Lentivirus to Express a CD33 Specific Chimeric Antigen Receptor in Patients With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia
A Phase 1 study testing Leukapheresis, Fludarabine and Cyclophosphamide in people with Hematopoietic/Lymphoid Cancer and Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this clinical research study is to learn about the safety and tolerability of 3 different doses of CD33-CAR-T cells (referred to throughout the consent as "T-cells") in patients who have CD33-positive… Read more about this study
- Who is it for?
- Ages 1 year to 80 years
- Conditions the study is for
- Hematopoietic/Lymphoid Cancer, Acute Myeloid Leukemia
- What is being tested?
- Leukapheresis, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2017to 10 Oct 2019
- 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 1 year to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 1-80 years of age. The pediatric cohort is defined as age younger than 18 years.
- Patients with active (blood or bone marrow blasts >5%) relapsed or refractory CD33+ acute myeloid leukemia (AML) de novo, or secondary. a. Relapsed AML is defined as patients that had a first complete remission (CR) before developing recurrent disease. b. Refractory AML defined as patients that have not achieved a CR after 2 cycles of induction chemotherapy.
- Patients must have bone marrow and peripheral blood studies available for confirmation of diagnosis of AML; CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry; cytogenetics, flow cytometry, and molecular studies (such as FMS-like tyrosine kinase-3 [Flt-3] status) will be obtained as per standard practice.
- ECOG performance status score </= 2.
- Pretreatment calculated or measured creatinine clearance (absolute value) of >= 60 mL/minute.
- Serum bilirubin =< 3.0 mg/dL.
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- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 times the institutional upper limits of normal.
- Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan (MUGA) >50%.
- Subject does not require supplemental oxygen or mechanical ventilation, and oxygen saturation by pulse oximetry is 94% or higher on room air.
- Negative serum pregnancy test.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
- Patients who have undergone allo-SCT are eligible if they are at least 3 months post SCT, have relapsed AML, are not on treatment or prophylaxis for GVHD, and have no active GVHD.
- All patients or legally responsible parent or guardian must have the ability to understand and willingness to sign a written informed consent
Who cannot join
- Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.
- Patients with extramedullary disease as their sole site of relapsed AML.
- Acceptable allogeneic stem cell donor with imminent plans to proceed with allo-SCT.
- Known central nervous system (CNS) leukemic involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that have been effectively treated to complete remission (< 5 white blood cell [WBC]/mm^3 and no blasts in cerebrospinal fluid [CSF]) will be eligible.
- Ongoing or active or uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements.
- Human immunodeficiency virus (HIV) seropositivity, or active hepatitis B or C infection based on testing performed within 4 weeks of enrollment.
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- Currently enrolled in another investigational therapy protocol for AML.
- Participants with presence of other active malignancy within 2 years of study entry; participants with history of prior malignancy treated with curative intent and achieved CR within 2 years are eligible.
- Pregnant and lactating women are excluded from this study
- Failure of research participant or legally responsible parent or guardian to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study.
- History of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab (anti-EGFR).
- History of allergic reactions to products containing mouse and bovine protein antibodies.
- Receiving corticosteroids at >20 mg (age >17) or >0.5mg/kg (age <18) daily prednisone dose or equivalent.
- Active autoimmune disease requiring systemic immunosuppressive therapy.
- Patient, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase 1 Safety Study of Adoptive Cellular Therapy Using Autologous T Cells Transduced With Lentivirus to Express a CD33 Specific Chimeric Antigen Receptor in Patients With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to learn about the safety and tolerability of 3 different doses of CD33-CAR-T cells (referred to throughout the consent as "T-cells") in patients who have CD33-positive acute myeloid leukemia (AML) that is relapsed (has come back) or refractory (has not responded to treatment).
Read more
CD33-CAR-T is made by genetically modifying (changing) your T-cells (a type of white blood cell). T-cells are genetically changed to help target leukemia cells.
This is an investigational study. CD33-CAR-T is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.
Up to 39 participants will be enrolled in this study. All will take part at MD Anderson.
- Being tested
- Leukapheresis, Fludarabine, Cyclophosphamide, CD33-CAR-T Cell Infusion
- Keywords
- Hematopoietic/Lymphoid Cancer, Acute Myeloid Leukemia, AML, Relapsed or Refractory CD33-Positive, CD33-CAR-T cells, Fludarabine, Fludarabine phosphate, Fludara, Cyclophosphamide, Cytoxan, Neosar
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeukapheresisProcedure or surgery
After enrollment, steady state leukapheresis performed to collect apheresis material. The goal is to achieve a target total nucleated cell (TNC) yield of at least 5 x 10^9 (expected range 5 x 10^8 - 5 x 10^10), for up to two days.
FludarabineDrug
Also called Fludarabine Phosphate, Fludara
25 mg/m2 administered by vein on Days -5 to -3.
CyclophosphamideDrug
Also called Cytoxan, Neosar
900 mg/m2 administered by vein on Day -3.
CD33-CAR-T Cell InfusionBiological
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. Starting dose level is > 1.5 x 105/kg but ≤ 4.5 x 105/kg.
| Study group | Role | What they receive |
|---|---|---|
| CD33-CAR-T cells - Adult Group | Experimental | After enrollment, steady state leukapheresis performed to collect apheresis material.
Fludarabine administered by vein on Days -5 to -3.
Cyclophosphamide administered by vein on Day -3.
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. Receives: Procedure: Leukapheresis; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CD33-CAR-T Cell Infusion |
| CD33-CAR-T cells - Pediatric Group | Experimental | After enrollment, steady state leukapheresis performed to collect apheresis material.
Fludarabine administered by vein on Days -5 to -3.
Cyclophosphamide administered by vein on Day -3.
CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. Receives: Procedure: Leukapheresis; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: CD33-CAR-T Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase II Dose (RP2D) of CD33-CAR-T Cells
RP2D defined as the highest dose level in which 6 patients have been treated with at most 1 instance of dose limiting toxicity (DLT).
DLT is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and occurring during the first course on study that meets any of the following criteria:
- CTCAE grades non-reversible grade 3, or any grade 4-5 allergic reactions related to the study cell infusion.
- CTCAE grades non-reversible grade 3, or any grade 4-5 autoimmune reactions related to the study cell infusion.
- CTCAE grades non-reversible grade 3, or any grade 4-5 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to the underlying malignancy and occurring within 28 days of study product infusion related to study cell infusion.
Measured: 28 days after completion of the CD33-CAR-T infusion
Secondary outcomes (1)
Disease Response to CD33-CAR-T Cells
Response to treatment evaluated according to the World Health Organization (WHO) standardized response criteria for myelodysplastic syndromes.
Disease response to CD33-CAR-T cells defined as Complete Remission (CR), Complete Remission without Platelet Recovery (CRp), Complete Remission without Neutrophil Recovery (CRn), Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR) or Non-responder (NR).
Measured: On Day 7, at Weeks 2, 4, and 8, and at Months 3, 6, and 12 after CD33-CAR-T Cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2017
- Study start4 Aug 2017
- Primary completion10 Oct 2019
- Study completion10 Oct 2019
Why it stopped: Terminated per the PI's request.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic/Lymphoid CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Intrexon Corporation
- Responsible party
- Sponsor
- Investigators
- William G. Wierda, MD, PHD, BS, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03126864
- Sponsor's protocol ID
- 2016-0341
- Other IDs
- NCI-2018-01167
- Status last verified
- Nov 2019
- First submitted
- 20 Apr 2017
- Last updated
- 4 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Safety Study of Adoptive Cellular Therapy Using Autologous T Cells Transduced With Lentivirus to Express a CD33 Specific Chimeric Antigen Receptor in Patients With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03126864
- Acronym / sponsor ID
- 2016-0341
- Keywords
- Hematopoietic/Lymphoid Cancer, Acute Myeloid Leukemia, AML, Relapsed or Refractory CD33-Positive, CD33-CAR-T cells, Fludarabine, Fludarabine phosphate, Fludara
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated per the PI's request.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Intrexon Corporation
- Study start
- 4 Aug 2017 (actual)
- Primary completion
- 10 Oct 2019 (actual)
- Study completion
- 10 Oct 2019 (actual)
- First posted
- 24 Apr 2017 (actual)
- 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.
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to learn about the safety and tolerability of 3 different doses of CD33-CAR-T cells (referred to throughout the consent as "T-cells") in patients who have CD33-positive acute myeloid leukemia (AML) that is relapsed (has come back) or refractory (has not responded to treatment).
CD33-CAR-T is made by genetically modifying (changing) your T-cells (a type of white blood cell). T-cells are genetically changed to help target leukemia cells.
This is an investigational study. CD33-CAR-T is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.
Up to 39 participants will be enrolled in this study. All will take part at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD33-CAR-T cells - Adult Group | Experimental | Procedure: Leukapheresis, Drug: Fludarabine, Drug: Cyclophosphamide, Biological: CD33-CAR-T Cell InfusionAfter enrollment, steady state leukapheresis performed to collect apheresis material. Fludarabine administered by vein on Days -5 to -3. Cyclophosphamide administered by vein on Day -3. CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. |
| CD33-CAR-T cells - Pediatric Group | Experimental | Procedure: Leukapheresis, Drug: Fludarabine, Drug: Cyclophosphamide, Biological: CD33-CAR-T Cell InfusionAfter enrollment, steady state leukapheresis performed to collect apheresis material. Fludarabine administered by vein on Days -5 to -3. Cyclophosphamide administered by vein on Day -3. CD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. |
Who may qualify
- Ages
- 1 year to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Age 1-80 years of age. The pediatric cohort is defined as age younger than 18 years.
- Patients with active (blood or bone marrow blasts >5%) relapsed or refractory CD33+ acute myeloid leukemia (AML) de novo, or secondary. a. Relapsed AML is defined as patients that had a first complete remission (CR) before developing recurrent disease. b. Refractory AML defined as patients that have not achieved a CR after 2 cycles of induction chemotherapy.
- Patients must have bone marrow and peripheral blood studies available for confirmation of diagnosis of AML; CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry; cytogenetics, flow cytometry, and molecular studies (such as FMS-like tyrosine kinase-3 [Flt-3] status) will be obtained as per standard practice.
- ECOG performance status score </= 2.
- Pretreatment calculated or measured creatinine clearance (absolute value) of >= 60 mL/minute.
Key exclusion criteria (15 listed)
- Diagnosis of acute promyelocytic leukemia (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.
- Patients with extramedullary disease as their sole site of relapsed AML.
- Acceptable allogeneic stem cell donor with imminent plans to proceed with allo-SCT.
- Known central nervous system (CNS) leukemic involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that have been effectively treated to complete remission (< 5 white blood cell [WBC]/mm^3 and no blasts in cerebrospinal fluid [CSF]) will be eligible.
- Ongoing or active or uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| LeukapheresisAfter enrollment, steady state leukapheresis performed to collect apheresis material. The goal is to achieve a target total nucleated cell (TNC) yield of at least 5 x 10^9 (expected range 5 x 10^8 - 5 x 10^10), for up to two days. | Procedure or surgery | CD33-CAR-T cells - Adult Group, CD33-CAR-T cells - Pediatric Group |
| FludarabineAlso: Fludarabine Phosphate, Fludara25 mg/m2 administered by vein on Days -5 to -3. | Drug | CD33-CAR-T cells - Adult Group, CD33-CAR-T cells - Pediatric Group |
| CyclophosphamideAlso: Cytoxan, Neosar900 mg/m2 administered by vein on Day -3. | Drug | CD33-CAR-T cells - Adult Group, CD33-CAR-T cells - Pediatric Group |
| CD33-CAR-T Cell InfusionCD33-CAR-T cell infusion administered by vein on Day 0. First group of participants receive the lowest dose level. Each new group will receive a higher dose than the one before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of T-cells is found. Starting dose level is > 1.5 x 105/kg but ≤ 4.5 x 105/kg. | Biological | CD33-CAR-T cells - Adult Group, CD33-CAR-T cells - Pediatric Group |
Primary outcome
Recommended Phase II Dose (RP2D) of CD33-CAR-T Cells
Time frame: 28 days after completion of the CD33-CAR-T infusion
RP2D defined as the highest dose level in which 6 patients have been treated with at most 1 instance of dose limiting toxicity (DLT). DLT is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and occurring during the first course on study that meets any of the following criteria: * CTCAE grades non-reversible grade 3, or any grade 4-5 allergic reactions related to the study cell infusion. * CTCAE grades non-reversible grade 3, or any grade 4-5 autoimmune reactions related to the study cell infusion. * CTCAE grades non-reversible grade 3, or any grade 4-5 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to the underlying malignancy and occurring within 28 days of study product infusion related to study cell infusion.
1 secondary outcome
Disease Response to CD33-CAR-T Cells
Time frame: On Day 7, at Weeks 2, 4, and 8, and at Months 3, 6, and 12 after CD33-CAR-T Cell infusion
Results and safety
The study was stopped early (reason given: Terminated per the PI's request.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
- University of Texas MD Anderson Cancer Center WebsiteLink 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.
William G. Wierda, MD, PHD, BS principal investigator
M.D. Anderson Cancer Center
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 Leukapheresis, Fludarabine and Cyclophosphamide in people with Hematopoietic/Lymphoid Cancer and Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center 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 13 inclusion and 15 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: stopped early, as of the sponsor's last update on 4 Nov 2019. 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 was stopped early (reason given: Terminated per the PI's request.). Results are not available in the source record.
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?
Recommended Phase II Dose (RP2D) of CD33-CAR-T Cells (time frame: 28 days after completion of the CD33-CAR-T infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2019.