Infusing donor lymphocytes after blood cancer transplants to reduce relapse risk

Phase I/II Study Using Prophylactic Donor Lymphocyte Infusion Early Post-Transplant After Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide for High-Risk Hematologic Malignancies

This study tests if giving special immune cells from a donor to patients with high-risk blood cancers after a transplant can help lower the chance of their cancer coming back.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 430 (estimated)
• Ages: 12 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: chemotherapy, cyclophosphamide
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05327023 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of donor lymphocyte infusions (DLI) in patients who have undergone allogeneic hematopoietic cell transplantation for high-risk hematologic malignancies. The study aims to determine if early administration of these lymphocytes can decrease the likelihood of cancer relapse. Participants will undergo a series of screenings and receive treatments that include cyclophosphamide and other immunotherapeutic agents. The trial focuses on patients with specific high-risk blood cancers who have not responded well to standard treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with high-risk leukemia, lymphoma, myelodysplastic syndrome, or multiple myeloma that is resistant to standard therapies.

Not a fit: Patients with low-risk hematologic malignancies or those who are not eligible for allogeneic hematopoietic cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly lower the risk of relapse in patients with high-risk blood cancers after transplantation.

How similar studies have performed: Previous studies have shown promise with donor lymphocyte infusions in preventing relapse, but this specific approach is being explored for the first time in this context.

Eligibility criteria

* INCLUSION CRITERIA:

Inclusion Criteria - Recipient

* Histologically or cytologically confirmed hematologic malignancy classified as high or very high disease risk by the Refined Disease Risk Index for HCT including one of the following:
* Acute myeloid leukemia (AML) with favorable cytogenetics (t(8;21), inv(16), t(15,17)) with induction failure (persistent disease without first achieving remission of any type) or active relapse
* AML with intermediate cytogenetics (not classified as favorable or adverse) with induction failure or active relapse (AML with intermediate cytogenetics in morphologic complete remission \[CR\] with minimal residual disease detectable by any modality also will be eligible)
* AML with adverse cytogenetics (complex karyotype with \>= 4 abnormalities) regardless of remission status
* Low risk myelodysplastic syndrome (MDS) (\<= 5% blasts, including chronic myelomonocytic leukemia) with adverse cytogenetics (abnormal chromosome 7 or \>= 4 abnormalities) with induction failure or active relapse
* High risk MDS (RAEB-1 or RAEB-2) with intermediate-risk cytogenetics (no abnormal chromosome 7 or \< 4 abnormalities) with induction failure or active relapse
* High risk MDS (RAEB-1 or RAEB-2) with adverse cytogenetics (abnormal chromosome 7 or \>= 4 abnormalities) regardless of remission status
* Acute lymphoblastic leukemia (ALL) in CR \>= 2 or with induction failure or active relapse (ALL in CR1 with minimal residual disease detected also will be eligible)
* Chronic myelocytic leukemia (CML) in blast crisis phase
* Hodgkin lymphoma with stable or progressive disease
* Mantle cell lymphoma with stable or progressive disease
* Relapsed Burkitt lymphoma in CR or partial remission (PR)
* Aggressive B-cell Non-Hodgkin Lymphoma (NHL) (e.g., diffuse large B-cell lymphoma, transformed indolent B-cell lymphoma) with stable or progressive disease
* T-cell NHL with stable or progressive disease
* Multiple myeloma (MM) with induction failure as defined by failure to achieve minimal response (CR, Very Good Partial Response \[VGPR\], or PR) or the development of progressive disease on primary therapy, or MM with active relapse as defined by previously treated myeloma that achieved a molecular response or better that then progressed
* Age 18-65 years.
* At least one potentially suitable HLA-haploidentical or HLA-matched donor
* Karnofsky performance score \>=60%
* Recipient participants must have adequate organ function as defined below:
* Cardiac ejection fraction \>=45% by 2D ECHO;
* Forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) all of \>=50% predicted;
* Estimated serum creatinine clearance of \>=60 ml/minute/1.73m2 calculated using eGFR in the clinical lab;
* Total bilirubin \<=2X the upper limit of normal;
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<=3X the upper limit of normal.
* Myeloablative conditioning is toxic to the developing human fetus and is teratogenic. For this reason, the following measures apply:
* Women of child-bearing potential (WOCBP) and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one-year post-transplant.
* WOCBP must have a negative serum or urine pregnancy test within 7 days prior to enrollment.

Inclusion Criteria - Donor

-Related donor (age \>=12) deemed suitable, eligible, and willing to donate, per clinical evaluations, who are additionally willing to donate blood, bone marrow, and stool for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation.

EXCLUSION CRITERIA:

Exclusion Criteria - Recipient

* Subjects who are receiving any other investigational agents. Prior experimental therapies must have been completed at least 3 weeks prior to the date of beginning conditioning.
* Prior myeloablative conditioning for autologous or allogeneic HCT.
* Active breastfeeding.
* Active malignancy of non-hematopoietic type (excluding non-melanoma skin cancers) which is metastatic, relapsed/refractory to treatment, or locally advanced and not amenable to curative treatment. This excludes non-melanoma skin cancers.
* Uncontrolled intercurrent illness (e.g. severe endocrinopathy, disseminated intravascular coagulation, profound electrolyte disturbance, active hepatitis, uncontrolled dental infection) that in the opinion of the PI would make it unsafe to proceed with transplantation.

Exclusion Criteria - Donor

None.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Christopher G Kanakry, M.D. — National Cancer Institute (NCI)
• Study coordinator: Amy H Chai

Conditions Hematologic Neoplasms; Prophylactic Donor Lymphocyte Infusions; Chronic Graft-Versus-Host Disease; Immunotherapeutic Strategies; myeloablative conditioning; Steroid-Refractory Grade