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New treatment option for Malignancy, Hematologic
Official title Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies
ClinicalTrials.gov ID: NCT06904066
What this study is testing
What is aldesleukin?
aldesleukin is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for malignancy, hematologic.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- Background: Blood cancers (such as leukemias) can be hard to treat, especially if they have mutations in the TP53 or RAS genes. These mutations can cause the cancer cells to create substances called neoepitopes.
- Phase 1: an early, usually small safety study
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 120
You may be able to join if
- Malignancy diagnosis requirements: -Eligible diagnoses include AML (acute myeloid leukemia), MDS (myelodysplastic syndrome), CMML(chronic...
- Detection of at least one of the neoepitope-forming TP53 or RAS mutations that are listed in Table 3 in on the TruSight Oncology (TSO) 500 sequencing...
- Presence of the correct HLA type needed to present one of the targeted neoepitopes as shown in Table 3. HLA typing data from any time-point prior to...
- For AML and MDS, bone marrow myeloblast percentage must be \>=5% of nucleated cells in either bone marrow aspirate or biopsy. Myeloblasts can be...
- For T-ALL, bone marrow T-cell blast percentage must be \>=5% of nucleated cells in either bone marrow aspirate or biopsy. T cells can be defined by...
You likely can't join if
- -For alloHSCT recipients only, people receiving any systemic immunosuppressive drugs including corticosteroids at doses of greater than 5 mg/day...
- Corticosteroids given for any indication at doses greater than 5 mg/day of prednisone or equivalent within 14 days before either apheresis or start...
- Participants with MDS/Myeloproliferative neoplasia overlap syndromes are not eligible.
- Participants with acute promyelocytic leukemia are not eligible.
- Participants who received a mis-matched sibling or haploidentical transplant are not eligible.
- Tumor masses \>=10 cm in largest diameter
See the full eligibility criteria
Who can join
- Malignancy diagnosis requirements: -Eligible diagnoses include AML (acute myeloid leukemia), MDS (myelodysplastic syndrome), CMML(chronic myelomonocytic leukemia), CML (chronic myeloid leukemia), and T-ALL (T-acute...
- Detection of at least one of the neoepitope-forming TP53 or RAS mutations that are listed in Table 3 in on the TruSight Oncology (TSO) 500 sequencing panel (NSR device) performed in the NCI Laboratory of Pathology is...
- Presence of the correct HLA type needed to present one of the targeted neoepitopes as shown in Table 3. HLA typing data from any time-point prior to apheresis can be used to meet this requirement. Table 3: Eligibility...
- For AML and MDS, bone marrow myeloblast percentage must be \>=5% of nucleated cells in either bone marrow aspirate or biopsy. Myeloblasts can be defined by immunohistochemistry or by cytochemistry stains including but...
- For T-ALL, bone marrow T-cell blast percentage must be \>=5% of nucleated cells in either bone marrow aspirate or biopsy. T cells can be defined by cytochemistry or immunohistochemistry or flow cytometry.
- For multiple myeloma, plasma cells having a phenotype consistent with multiple myeloma must be detected at any frequency by multiparameter bone marrow flow cytometry or total plasma cells must be at least 6% on bone...
- For CMML, bone marrow blast (including monocytic blast equivalent) percentage must be \>=6% of bone marrow nucleated cells by cytochemistry or immunohistochemistry of bone marrow aspirate or biopsy.
- For CML measurable leukemia is defined as molecular detection of BCR-ABL1 at a ratio of \>1.0% to ABL1 or another housekeeping gene on The International Scale (IS) in either blood or bone marrow. Malignancy prior...
- Participants with primary, secondary, or treatment-related AML that did not go into remission after induction therapy are eligible regardless of history of alloHSCT.
- Myelodysplastic syndrome (MDS)
- Participants with MDS must have had high or very high risk MDS as determined by IPSS-R or IPSS-M (https://mds-risk-model.com) at any time point.
- Participants with MDS must have received previous treatment with at least one of the following: a hypomethylating agent, cytotoxic chemotherapy, or alloHSCT. Participants with primary or treatment-related MDS are...
- Participants with MDS/AML with mutated TP53 are eligible.
- Participants with CMML must have had a CMML-specific prognostic scoring system-Molecular (CPSS-Mol) score of \>=2 (Intermediate-2 or High risk groups) at any time-point and must have received at least one line of...
- Chronic myeloid leukemia (CML)
- Participants with chronic phase CML and a history of inadequate response to or intolerance of 3 or more tyrosine kinase inhibitors (TKIs) are eligible.
- In addition, participants who have received at least one of bosutinib, dasatinib, or nilotinib in addition to either ponatinib or asciminib are eligible. Participants in accelerated phase or blast crisis are eligible if...
- Participants who have received a prior HSCT are eligible provided they have also received at least 2 TKIs and meet other eligibility criteria.
- Participants with T-ALL must have T-ALL that did not go into CR with induction therapy or that relapsed.
- Participants with relapsed AML who are unable to undergo alloHSCT and meet other eligibility requirements are eligible.
- Multiple Myeloma
- Participants with multiple myeloma must have received at least 3 different prior systemic treatment regimens for multiple myeloma. Participants must have prior exposure to an imid such as lenalidomide, a proteosome...
- Multiple myeloma participants with a history of alloHSCT are eligible
- Participants with multiple myeloma must also have measurable multiple myeloma defined by at least one of the criteria below:
- Serum M-protein greater or equal to 1.0 g/dL.
- Urine M-protein greater or equal to 200 mg/24 h.
- Serum free light chain (FLC) assay: involved FLC level greater or equal to 10mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
- A biopsy-proven plasmacytoma at least 2.0 cm in largest dimension.
- Bone marrow core biopsy with 30% or more plasma cells. Other Blast cells \<=1% of white blood cells as measured by CBC and differential before apheresis
- Plasma cells \<=1% of white blood cells as measured by CBC and differential before apheresis
- Participants must be willing to undergo intensive care unit care including mechanical ventilation if necessary
- Participants must not have received systemic chemotherapy for at least 14 days prior to start of lymphodepleting chemotherapy or apheresis, and chemotherapy-related toxicities other than cytopenias must have recovered...
- Participants who have received alloHSCT must have received a transplant from either a fully matched sibling or 10/10 HLA-matched unrelated donor.
- Recipients of alloHSCT must be at least 100 days post-transplant before the apheresis.
- people must be willing to be co-enrolled on NCI protocol 03C0277 and 09C0161.
- Age must be \>=18 and \<= 75 years old
- Clinical performance status of ECOG 0 or 1
- Participants must have adequate organ function as defined below:
- Hemoglobin: \>=8 g/dL without red blood cell transfusions for 7 days prior to blood count check
- Platelets: \>=45,000/mcL without transfusion support in the 7 days prior to the blood count check
- Absolute neutrophil count: \>=850/mcL without exogenous growth factor administration within the 10 days prior to the blood count check
- Total bilirubin: \<= 2.0 mg/dL. Except for participants with Gilbert s syndrome (who must have a total bilirubin \<3 mg/dL)
- Alanine transaminase (ALT) and aspartate transaminase (AST): \<= to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. If liver involvement with malignancy is...
- Serum Creatinine: \<= 1.5 mg/dL
- Participants who have received prior genetically-engineered T-cell therapies are eligible if at least 180 days have elapsed between the date of previous T-cell infusion and apheresis.
- Room air oxygen saturation must be 93% or greater
- Women of child-bearing potential (WOCBP) must agree to use highly effective contraception (hormonal, intrauterine device [IUD], abstinence, surgical sterilization) starting at the time of study entry, for the duration...
- Nursing participants must be willing to discontinue breastfeeding from study treatment initiation through 4 months after the last dose of the study drug(s).
- Hepatitis B surface antigen and hepatitis B core antibody tests must be negative. If either of these tests are positive, participants must have a negative blood PCR test for hepatitis B to enroll on the study.
- Hepatitis C antibody test must be negative. If this test is positive, participants must have a negative blood PCR test for hepatitis C RNA to enroll on the study.
- Cardiac ejection fraction of greater than or equal to 50% by echocardiography with no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 30 days prior to apheresis.
- All participants must be willing to undergo mandatory bone marrow biopsy/ aspirates during the study.
- Participants with a history of cigarette smoking of \>5 pack years, a history of pulmonary disease, a history of alloHSCT, or chronic pulmonary symptoms must undergo pulmonary function testing and have an FEV1 \>50%...
- people who received a previous allogeneic HSCT must have no (grade 0) acute GVHD and no chronic GVHD or mild chronic GVHD as defined. --NOTE: people with GVHD meeting the above criteria with local therapy (topical...
- Potential participants must agree to stay within 1-hour drive of NIH clinical center from date of initial discharge until at least 14 days have elapsed since T cell infusion through the 14 day time period.
- Ability of the participant to understand and the willingness to sign a written informed consent document.
- Willing to sign a durable power of attorney.
What rules you out
- -For alloHSCT recipients only, people receiving any systemic immunosuppressive drugs including corticosteroids at doses of greater than 5 mg/day prednisone or equivalent within 28 days prior to apheresis. NOTE: Topical...
- Corticosteroids given for any indication at doses greater than 5 mg/day of prednisone or equivalent within 14 days before either apheresis or start of protocol chemotherapy.
- Participants with MDS/Myeloproliferative neoplasia overlap syndromes are not eligible.
- Participants with acute promyelocytic leukemia are not eligible.
- Participants who received a mis-matched sibling or haploidentical transplant are not eligible.
- Tumor masses \>=10 cm in largest diameter
- Positive beta Human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in IOCBP performed at screening.
- Human T-cell lymphotropic virus type 1/ 2 (HTLV-1/II) positive
- HIV infection, as measured by seropositivity for HIV antibody.
- Participants that require urgent therapy due to tumor mass effects on vital organ or tumor lysis syndrome.
- Any significant illness that, in the opinion of the principal investigator, may impair the participant s tolerance of the study treatment as evaluated by medical history, physical exam, assess for hepatosplenomegaly...
- Participants with a history of a previous malignancy are ineligible if the malignancy has not been in complete remission for at least 2 years or if the previous malignancy required treatment with surgery, radiation, or...
- Suspected or confirmed active uncontrolled infections defined as fevers of \>38 degrees within the past 24 hours without a known non-infectious source or participants requiring intravenous antibiotics when intravenous...
- Acti...
The study team makes the final eligibility decision.
Where it's taking place
- Bethesda, Maryland, United States
Compensation & support
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years to 120 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Bethesda, Maryland, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.