A Phase 1/2 interventional study of donor lymphocyte infusion and Cyclophosphamide in Hematologic Neoplasms, sponsored by National Cancer Institute (NCI). Recruiting at 1 site in United States. Open to participants aged 12 Years to 120 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-09.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
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....
Background:
Objectives:
-To determine the maximally tolerated dose of DLI that can be safely administered after HLA-matched-related HCT and after HLA-haploidentical HCT
Eligibility:
-Recipient Participant:
Design:
1,444 studies on the registry are indexed under Hematologic Neoplasms; 420 are open to participants now.
This study's planned enrollment of 430 is above the median of 46 across 1,044 interventional studies indexed under Hematologic Neoplasms.
Browse Hematologic Neoplasms studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria - Recipient:
or cytologically confirmed hematologic classified as high or very high disease risk by the Refined Disease Risk Index for HCT including one of the following:
Recipient participants must have adequate organ function as defined below:
Myeloablative conditioning is toxic to the developing human fetus and is teratogenic. For this reason, the following measures apply:
--Women of (WOCBP) and men must agree to use effective (hormonal, surgical, IUD or barrier method of birth control; abstinence) from the start of conditioning regimen through at least one-year posttransplant. For the HLA haploidentical cohort the requirements are the same, however while taking sirolimus and for 12 weeks after the last dose, the birth control must be highly effective (hormonal, surgical, IUD, abstinence).
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:
Exclusion Criteria - Donor:
None.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Donors for Recipients in Arms 1-4
DLI at escalating doses (1 x 10\^6 CD3+ cells/kg, 3 x 10\^6 CD3+ cells/kg, and 1 x 10\^7 CD3+ cells/kg) on day +7 or +21 to assess for safety and determine Phase II dose (up to 18 evaluable patients)
Procedure: donor lymphocyte infusion · Drug: Cyclophosphamide · Drug: Busulfan · Drug: Mycophenolate mofetil · Drug: Fludarabine · Drug: Sirolimus
DLI at escalating doses (1 x 10\^5 CD3+ cells/kg, 3 x 10\^5 CD3+ cells/kg, and 1 x 10\^6 CD3+ cells/kg) on day +7 or +21 to assess for safety and determine Phase II dose (up to 18 evaluable patients)
Procedure: donor lymphocyte infusion · Drug: Cyclophosphamide · Drug: Busulfan · Drug: Mycophenolate mofetil · Drug: Fludarabine · Drug: Sirolimus
DLI at maximally tolerated, safe dose (from Phase I) to assess secondary clinical outcomes at this dosing level (up to 14 additional evaluable patients in each cohort)
Procedure: donor lymphocyte infusion · Drug: Cyclophosphamide · Drug: Busulfan · Drug: Mycophenolate mofetil · Drug: Fludarabine · Drug: Sirolimus
DLI at maximally tolerated, safe dose (from Phase I) to assess secondary clinical outcomes at this dosing level (up to 14 additional evaluable patients in each cohort)
Procedure: donor lymphocyte infusion · Drug: Cyclophosphamide · Drug: Busulfan · Drug: Mycophenolate mofetil · Drug: Fludarabine · Drug: Sirolimus
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.
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.
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
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.
40 mg/m2 IV infusion over 30-60 minutes once daily for 4 days Transplant days -6 through -3
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.
determine the maximally tolerated dose of DLI that can be safely administered after HLA-matched-related HCT and after HLA-haploidentical HCT
fraction of evaluable patients who experience steroid-refractory grade III-IV aGVHD at day +60 will be determined and reported along with 80% and 95% two-sided confidence intervals.
Time frame: 60 days
determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of Steroid-refractory Grades II-IV and Grades III-IV aGVHD at days +100 and +200 for HLA-matched-related and HLA-haploidentical
To evaluate steroid-refractory grade II-IV and grade III-IV acute GVHD at day 100 and 200.
Time frame: Day 100 and 200
determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of chronic GVHD at 1 year for HLA-matched-related and HLA-haploidentical
To evaluate chronic GVHD
Time frame: 1 year
determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of Grades II-IV and Grades III-IV aGVHD at days +100 and +200 for HLA-matched-related and HLA-haploidentical
To evaluate grade II-IV and grade III-IV acute GVHD at day 100 and 200.
Time frame: Day 100 and 200
determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of non-relapse mortality at 100 days and 1 year for HLA-matched-related and HLA-haploidentical
To evaluate non-relapse mortality
Time frame: Day 100 and 1 year
determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of relapse at 1 year for HLA-matched-related and HLA-haploidentical
To evaluate relapse
Time frame: 1 year
determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of overall survival (OS) and disease-free survival (DFS) at 1 year for HLA-matched-related and HLA-haploidentical
To evaluate survival
Time frame: 1 year
determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of primary engraftment (including time to neutrophil and platelet engraftment) for HLA-matched-related and HLA-haploidentical
Rate and timing of neutrophil and platelet engraftment reported as median engraftment times for each and cumulative incidences of each at days +28 and +100
Time frame: Day 28 and 100
Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.
Started May 2022 (actual). Primary completion is estimated for Jul 2028, 73 months after the start.
Of 64 phase 1/2 interventional studies under Hematologic Neoplasms, half reached primary completion within 76 months of starting (the median), counting those still running; a quarter within 51 and three quarters within 127. This study's planned 73 months is close to that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drug tested here: Cyclophosphamide
National Cancer Institute (NCI) →