Phase I/II Study of CAR.70- Engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Hematological Malignances
2 other identifiers
interventional
80
1 country
1
Brief Summary
The goal of this clinical research study is to learn about the safety of giving immune cells called natural killer (NK) cells with chemotherapy to patients with leukemia, lymphoma, or multiple myeloma. Immune system cells (such as NK cells) are made by the body to attack foreign or cancerous cells. Researchers think that NK cells you receive from a donor may react against cancer cells in your body, which may help to control the disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2021
CompletedFirst Posted
Study publicly available on registry
October 25, 2021
CompletedStudy Start
First participant enrolled
November 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2026
May 6, 2026
May 1, 2026
3.8 years
October 13, 2021
May 5, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0.
CTCAE Version 5.0 - General grading: Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required beyond prophylaxis. Grade 2: Moderate: discomfort present with some disruption of daily activity, require treatment. Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first line treatment. Grade 4: Life Threatening: discomfort that represents immediate risk of death
through study completion, an average of 1 year
Number of Participants with Complete or Partial Response
Up to 30 days after the last treatment
Number of Participants who are Alive and in Remission
Number of Participants who are Alive and in Remission after 6 months.
Up to 180 days
Study Arms (3)
Cyclophosphamide
EXPERIMENTALCyclophosphamide is dosed per adjusted body weight for patients weighing \> 20% above their ideal body weight using the calculation.
CAR.70/IL15-transduced CB-NK cells
EXPERIMENTALPatients will receive a single flat dose of CAR-NK.
Fludarabine phosphate
EXPERIMENTALFludarabine is dosed using actual body weight.
Interventions
Given by IV
Given by IV
Eligibility Criteria
You may qualify if:
- Patients with hematological malignances with an expression of CD70 in the pre-enrollment tumor sample ≥ 10% measured by immunohistochemistry or flow cytometry.
- Patients must meet diseases specific eligibility criteria (see below)
- Patients at least 1 week from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheral blood count control in AML, CML, and MDS patients until the day prior to administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy.
- Localized radiotherapy to one or more disease sites is allowed prior the infusion provided that there are additional disease sites that are not irradiated to assess response
- Karnofsky Performance Scale \> 50% for patients who are \>16 years old or Lansky score ≥50% for patients who are ≤16 years of age.
- Adequate organ function:
- Renal: Serum creatinine \</= 2x ULN or estimated Glomerular Filtration Rate \>/= 30 ml/min/1.73 m2
- Hepatic: ALT/AST \</= 3 x ULN or \</= 5 x ULN if documented liver metastases, Total bilirubin \</2xULN, except in subjects with Gilbert's Syndrome in whom total bilirubin must be \</= 3 x.ULN. No history of liver cirrhosis. No ascites.
- Cardiac: Cardiac ejection fraction \>/= 40%, no clinically significant pericardial effusion as determined by an ECHO, and no uncontrolled arrhythmias or symptomatic cardiac disease.
- Pulmonary: No clinically significant pleural effusion (per PI discretion), baseline oxygen saturation \> 92% on room air and adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) \>50%.
- Able to provide written informed consent.
- years of age.
- Weight ≥40 kg
- All participants who are able to have children must practice effective birth control while on study and up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
- Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.
- +1 more criteria
You may not qualify if:
- Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
- Presence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by PI.
- Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy.
- HIV with detectable viral load
- Presence of active neurological disorder(s).
- Active autoimmune disease within 12 months of enrollment
- Amyloidosis or POEMS syndrome
- Active cerebral or meningeal involvement by the malignancy
- Active (defined as requiring therapy) acute or chronic GVHD
- Any other malignancy known to be active, except for treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
- Presence of any other serious medical condition that may endanger the patient at investigator discretion.
- Major surgery \<4 weeks prior to first dose of the preparatory chemotherapy
- Allogeneic SCT or DLI \<12 weeks prior to first dose of preparatory chemotherapy
- Concomitant use of other investigational agents.
- Concomitant use of other anti-cancer agents.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Lin P, Acharya S, Reyes-Silva F, Basar R, Uprety N, Moreno Rueda LY, Lin P, Gilbert AL, Banerjee PP, Fang D, Zhang C, Nunez Cortes AK, Melo Garcia L, Daher M, Muniz-Feliciano L, Deyter GM, Woods V, Rawal S, Li P, Jones CM, Shrestha R, Qazilbash MH, Patel KK, Lee HC, Champlin RE, Marin D, Shpall EJ, Orlowski RZ, Rezvani K. CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models. Blood Cancer Discov. 2026 Mar 4;7(2):234-249. doi: 10.1158/2643-3230.BCD-25-0130.
PMID: 41144785DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David Marin, MD
M.D. Anderson Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 13, 2021
First Posted
October 25, 2021
Study Start
November 1, 2022
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
August 31, 2026
Last Updated
May 6, 2026
Record last verified: 2026-05