Using engineered immune cells with chemotherapy to treat blood cancers

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

This study is testing if using special immune cells along with chemotherapy can help people with tough-to-treat blood cancers like B-cell lymphoma and leukemia feel better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 12 Years to 80 Years
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: alemtuzumab, chemotherapy
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT05092451 on ClinicalTrials.gov

What this trial studies

This clinical research focuses on the safety and efficacy of administering CAR.70/IL15-transduced cord blood-derived natural killer (NK) cells alongside lymphodepleting chemotherapy in patients with relapsed or refractory hematological malignancies. The study aims to identify the optimal cell dose and assess the persistence of these engineered NK cells in the patient's body. By leveraging the body's immune response, the researchers hope to enhance the treatment of conditions such as B-cell lymphoma, acute myeloid leukemia, and multiple myeloma.

Who should consider this trial

Good fit: Ideal candidates include patients with hematological malignancies expressing CD70 in their tumor samples and who meet specific disease-related eligibility criteria.

Not a fit: Patients without CD70 expression in their tumors or those who are not eligible based on the study's criteria may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this approach could provide a novel and effective treatment option for patients with difficult-to-treat blood cancers.

How similar studies have performed: Other studies utilizing engineered NK cells have shown promising results, indicating potential success for this novel approach.

Eligibility criteria

Inclusion criteria:

1. Patients with hematological malignances with an expression of CD70 in the pre-enrollment tumor sample ≥ 10% measured by immunohistochemistry or flow cytometry.
2. Patients must meet diseases specific eligibility criteria (see below)
3. 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.
4. 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
5. Karnofsky Performance Scale \> 50% for patients who are \>16 years old or Lansky score ≥50% for patients who are ≤16 years of age.
6. Adequate organ function:

   1. Renal: Serum creatinine \</= 2x ULN or estimated Glomerular Filtration Rate \>/= 30 ml/min/1.73 m2
   2. 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.
   3. Cardiac: Cardiac ejection fraction \>/= 40%, no clinically significant pericardial effusion as determined by an ECHO, and no uncontrolled arrhythmias or symptomatic cardiac disease.
   4. 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%.
7. Able to provide written informed consent.
8. 12-80 years of age.
9. Weight ≥40 kg
10. 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.
11. Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.
12. Are willing and able to provide informed consent, as appropriate (either directly or through a legally authorized representative \[LAR\])

Exclusion criteria:

1. Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
2. Presence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by PI.
3. Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy.
4. HIV with detectable viral load
5. Presence of active neurological disorder(s).
6. Active autoimmune disease within 12 months of enrollment
7. Amyloidosis or POEMS syndrome
8. Active cerebral or meningeal involvement by the malignancy
9. Active (defined as requiring therapy) acute or chronic GVHD
10. Any other malignancy known to be active, except for treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
11. Presence of any other serious medical condition that may endanger the patient at investigator discretion.
12. Major surgery \<4 weeks prior to first dose of the preparatory chemotherapy
13. Allogeneic SCT or DLI \<12 weeks prior to first dose of preparatory chemotherapy
14. Concomitant use of other investigational agents.
15. Concomitant use of other anti-cancer agents.
16. Patients receiving systemic steroid therapy at time of NK cell infusion (physiological substitutive doses are allowed), or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment.
17. Patients receiving immunosuppressive therapy

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: David Marin, MD — M.D. Anderson Cancer Center
• Study coordinator: David Marin

Conditions B-Cell Lymphoma; Myelodysplastic Syndromes; Acute Myeloid Leukemia; Multiple Myeloma; Plasma Cell Leukemia; Hodgkin Lymphoma; T-cell Non-Hodgkin's Lymphoma/ T-cell Acute Lymphoblastic Leukmeia; Myelodysplastic Syndrome / Chronic Myelomonocytic Leukemia