RecruitingPhase 1Phase 2NCT05327023

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

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


Sponsor

National Cancer Institute (NCI)

Enrollment

430 participants

Start Date

May 23, 2022

Study Type

INTERVENTIONAL

Conditions

Summary

Background: People with blood cancers often receive blood or bone marrow transplants. But even with these treatments, the risk of relapse is high. Researchers want to see if giving the transplant recipient an infusion of lymphocytes (a type of white blood cell) from their transplant donor early after the transplant can reduce that risk. Objective: To learn if giving donor lymphocytes early after a transplant will help reduce the risk of relapse for people with certain blood cancers. Eligibility: Adults aged 18-65 with high-risk leukemia, lymphoma, myelodysplastic syndrome, or multiple myeloma that does not respond well to standard treatments and/or has a high risk of relapse. Healthy potential bone marrow and lymphocyte donor relatives aged 12 and older are also needed. Design: Participants will be screened with: Physical exam Blood and urine tests Spinal tap Eye exam Dental exam Heart and lung tests Imaging scans. A radioactive substance may be injected in their arm if a PET scan is needed. Bone marrow aspiration and biopsy Some screening tests will be repeated during the study. Participants will stay at the NIH hospital for about 4 weeks. They will receive a central venous catheter. They will get chemotherapy and other drugs starting 6 days before transplant. Then they will have their transplant. They will receive donor white blood cells 7 days later. They will give blood, bone marrow, urine, and stool samples for research. They must stay near NIH for at least 100 days after transplant. Participants will have periodic follow-up visits for 5 years. Healthy donors will have 2-3 visits. They will give blood, bone marrow, white blood cells, and stool samples for research. Participation will last for 5 years....


Eligibility

Min Age: 12 YearsMax Age: 120 Years

Plain Language Summary

Simplified for easier understanding

This study tests whether giving immune cells from a donor (called donor lymphocyte infusion) after a stem cell transplant can help fight high-risk blood cancers like leukemia, lymphoma, or multiple myeloma. **You may be eligible if...** - You are 18–65 years old - You have a high-risk blood cancer such as AML, ALL, MDS, CML, lymphoma, or multiple myeloma - You have a suitable matched or half-matched donor available - Your heart, lungs, kidneys, and liver are functioning well enough - You have a performance score showing you can carry out normal activity **You may NOT be eligible if...** - You have had a prior stem cell transplant with full-intensity conditioning - You are currently enrolled in another clinical trial - You have an active cancer other than your blood cancer - You are currently breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDUREdonor lymphocyte infusion

The DLI will be given on Day +7 (Day +21 for dose level -1). If a recipient participant is deemed too critically ill/unstable to receive DLI on the protocol specified day, the DLI will be delayed up to 4 days at the discretion of the PI and given within this time frame once the recipient participant s clinical status has stabilized or improved. If the DLI cannot be given during this time frame, the recipient participant will be taken off study and not considered evaluable for DLT, outcomes, or adverse events since the experimental intervention will not have been given.

DRUGCyclophosphamide

HLA-matched: 50 mg/kg IV once daily over 2 hours on days +3 and +4a Cyclophosphamide will be dosed according to ideal body weight. HLA haploidentical: 25 mg/kg IV once daily over 2 hours on days +3 and +4a Cyclophosphamide will be dosed according to ideal body weight.

DRUGBusulfan

AUC targeted dose based on busulfan test dose, with a default dose of 130 mg/m2/day, given as IV infusion over 3 hours each day for 4 days Transplant days -6 through day -3

DRUGMycophenolate mofetil

15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35. Dosing will be according to actual body weight.

DRUGFludarabine

40 mg/m2 IV infusion over 30-60 minutes once daily for 4 days Transplant days -6 through -3

DRUGSirolimus

Loading dose of 6 mg orally given on day +5 (calculated based on actual body weight, maximum initial dose 6 mg), then maintenance dose starting at 2 mg orally daily on day +6 with dose adjustments to maintain a trough of 5-12 ng/ml, continued through day +70 with no taper. Doses should be modified as appropriate for drug interactions.


Locations(1)

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

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NCT05327023


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