Phase I/II Study of CD5 CAR Engineered IL15-Transduced Cord Blood-Derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Hematological Malignances

NCT05110742 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0526NCI-2021-10898
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the safety, efficacy and optimal cell dose of CAR 5/IL15-transduced CB-NK cells in patients with relapsed/refractory T-cell malignances, mantle cell lymphoma, and chronic lymphocytic leukemia. The efficacy and optimal dose will be identified for individual diseases.

Conditions

Hematological Malignancy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events as Assessed by 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

Study Arms (2)

Phase 1 Dose Level

EXPERIMENTAL

CAR.5/IL15-transduced CB-NK cells Dose level 1, 1e7 cryopreserved cells flat dose Dose level 2, 1e8 cryopreserved cells flat dose Dose level 3, 1e9 cryopreserved cells flat dose Dose level 4, 1e10 cryopreserved cells flat dose All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.

Drug: Fludarabine Phosphate; Drug: Cyclophosphamide; Drug: CAR.5/IL15-transduced CB-NK cells

Phase 2 Dose Level

EXPERIMENTAL

Patients will be randomized between the 2 optimal doses of CAR.5/IL15-transduced CB-NK cells determined by Phase 1. All patients will receive Lymphodepleting Chemotherapy of Cyclophosphamide and Fludarabine.

Drug: Fludarabine Phosphate; Drug: Cyclophosphamide; Drug: CAR.5/IL15-transduced CB-NK cells

Interventions

Cyclophosphamide DRUG

Given by IV

Also known as: Cytoxan®, Neosar®

Phase 1 Dose Level; Phase 2 Dose Level

Fludarabine Phosphate DRUG

Given by IV

Also known as: Fludarabine, Fludara®

Phase 1 Dose Level; Phase 2 Dose Level

CAR.5/IL15-transduced CB-NK cells DRUG

Given by IV

Phase 1 Dose Level; Phase 2 Dose Level

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with hematological malignances with an expression of CD5 in the pre-enrollment tumor sample ≥ 30% measured by immunohistochemistry or flow cytometry.
• Patients must meet diseases specific eligibility criteria (see below)
• Patients should be at least 1 weeks from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until at least three days prior to administration of lymphodepleting chemotherapy.
• Localized radiotherapy to one or more disease sites are allowed prior the infusion provided that there are additional disease sites that are not irradiated.
• Karnofsky Performance Scale \> 50%.
• Adequate organ function:
• Renal: Serum creatinine ≤ 2.0ULN or estimated Glomerular Filtration Rate (eGFR using the CKI-EPI equation) ≥ 30 ml/min/1.73 m2.
• Hepatic: ALT/AST ≤ 3.0 x ULN or ≤ 5 x ULN if documented liver involvement with disease, Total bilirubin ≤ 2.0ULN, except in subjects with Gilbert's Syndrome in whom total bilirubin must be ≤ 3.0 mg/dL. No history of liver cirrhosis.
• Cardiac: Cardiac ejection fraction ≥ 40%, no clinically significant pericardial effusion as determined by an ECHO or MUGA, and no uncontrolled arrhythmias or symptomatic cardiac disease.
• Pulmonary: No clinically significant lung involvement, per PI discretion, pleural effusion, baseline oxygen saturation \> 92% on room air.
• Able to provide written informed consent.
• years of age.
• Weight ≥40 kg.
• English and non-English speaking patients are eligible.
• 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.

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.
• Active hepatitis B or C.
• HIV with detectable viral load.
• Presence of active neurological disorder(s).
• Active autoimmune disease within 12 months of enrollment
• 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 criteria.
• Major surgery \<4 weeks prior to first dose of study drug
• Allogeneic SCT or DLI \<12 weeks prior to first dose of study drug. Recipients of an allogeneic SCT patients should have discontinued all forms of immunosuppression at least 8 weeks prior enrollment in the study.
• Concomitant use of other investigational agents.
• Concomitant use of other anti-cancer agents.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

fludarabine phosphate; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• chitra hosing

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chitra Hosing

CONTACT

(713) 745-3219; cmhosing@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: November 8, 2021
• Study Start: April 22, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (1)