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

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....

Conditions

• Hematologic Neoplasms

Interventions

PROCEDURE

donor 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.

DRUG

Cyclophosphamide

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.

DRUG

Busulfan

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

DRUG

Mycophenolate 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.

DRUG

Fludarabine

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

DRUG

Sirolimus

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Christopher G Kanakry, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

12 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-05-23

Primary Completion

2028-07-03

Completion

2029-07-02

FDA Drug

Yes

Countries

• United States

Study Locations