Hematologic NeoplasmsPhase 1/2NCT04959175
Phase I/II Study to Reduce Post-transplantation Cyclophosphamide Dosing for Older or Unfit Patients Undergoing Bone Marrow Transplantation for Hematologic Malignancies
A Phase 1/2 study testing Mycophenolate Mofetil, Allogeneic HSCT and Fludarabine in people with Hematologic Neoplasms, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
Background: Certain blood cancers can be treated with blood or bone marrow transplants. Sometimes the donor cells attack the recipient's body, called graft-versus-host disease (GVHD). The chemotherapy drug cyclophosphamide helps reduce the risk and severity of GVHD. Read more about this study
- Who is it for?
- Ages 12 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Hematologic Neoplasms
- What is being tested?
- Mycophenolate Mofetil, Allogeneic HSCT and Fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Sep 2021to 30 Apr 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 85 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Related (age >=12) and unrelated (age >=18) donors deemed eligible (i.e., evaluated at NIH in accordance with existing institutional Standard Policies and Procedures or evaluated per the standards required by the IRB of the National Marrow Donor Program or applicable registry), and willing to donate research samples will be included.
Who cannot join
- Subjects who are receiving any other investigational agents. Prior experimental therapies must have been completed at least 2 weeks prior to the date of beginning conditioning.
- Poorly controlled malignant indication for transplantation such as:
- Leukemia not having achieved morphologic remission (i.e. bone marrow blasts >5% or active extramedullary disease)
- Lymphoma not having achieved at least a partial response to prior chemotherapy or radiation
- Uncontrolled intercurrent illness that in the opinion of the site PI would make it unsafe to proceed with transplantation.
- The potential for some of the study medications to be transmissible via breast milk of nursing mothers is unknown. Because there is unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued.
- Active malignancy of non-hematopoietic type which is: metastatic, relapsed/refractory to treatment, or locally advanced and not amenable to curative treatment, or limited disease treated with curative intent treatment within the last 2 years. This excludes nonmelanoma skin cancers.
- None
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
- Recruiting
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Shannon McCurdy, 215-614-0698, shannon.mccurdy@pennmedicine.upenn.edu
About this study
Background:
Certain blood cancers can be treated with blood or bone marrow transplants. Sometimes the donor cells attack the recipient's body, called graft-versus-host disease (GVHD). The chemotherapy drug cyclophosphamide helps reduce the risk and severity of GVHD. Researchers want to learn if using a lower dose of cyclophosphamide may reduce the drug's side effects while maintaining its effectiveness. Such an approach is being used in an ongoing clinical study at the NIH with promising results, but this approach has not been tested for transplants using lower doses of chemotherapy/radiation prior to the transplant.
Read more
Objective:
To learn if using a lower dose of cyclophosphamide will help people have a successful transplant and have fewer problems and side effects.
Eligibility:
Adults ages 18-85 who have a blood cancer that did not respond well to standard treatments or is at high risk for relapse without transplant, and their donors.
Design:
Participants may be screened with the following:
Medical history
Physical exam
Blood and urine tests
Heart and lung tests
Body imaging scans (they may get a contrast agent)
Spinal tap
Bone marrow biopsy
Participants will be hospitalized for 4-6 weeks. They will have a central venous catheter placed in a chest or neck vein. It will be used to give medicines, transfusions, and the donor cells, and to take blood. In the week before transplant, they will get 2 chemotherapy drugs and radiation. After the transplant, they will get the study drug for 2 days. They will take other drugs for up to 2 months.
Participants must stay near NIH for 3 months after discharge for weekly study visits. Then they will have visits every 3-12 months until 5 years after transplant.
Participants and donors will give blood, bone marrow, saliva, cheek swab, urine, and stool samples for research.
Read the detailed description
Background:
With novel therapies for hematologic malignancies, an increasing number of older and/or less fit patients are achieving remissions, but these new therapies are not curative, making consolidation approaches with curative intent such as allogeneic transplantation necessary.
Frailty is a phenotype that predicts a patient s intolerance of physiologic stressors and may predict a patient s tolerance of intensive consolidative strategies.
Frailty phenotype, though increasing in incidence in older patients, can occur in younger patients and may predict poor survival after allogeneic transplantation.
We have yet to define the ideal allogeneic transplantation regimen for older patients or those with frailty or pre-frail phenotypes.
Post-transplantation cyclophosphamide (PTCy) reduces rates of severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) and safely facilitates human leukocyte antigen (HLA)-matched-related, HLA-matched-unrelated, HLA-mismatched-unrelated, and HLA-haploidentical HCT; it has become the most widely adopted change to transplantation platforms over the last decade.
When clinically translated, the dose (50 mg/kg/day) of PTCy used was partly extrapolated from murine major histocompatibility complex (MHC)-matched skin allografting models and was partly empirical.
In both MHC-haploidentical and MHC-disparate murine HCT models, a dose of 25 mg/kg/day was superior to 50 mg/kg/day on days +3 and +4 in terms of GVHD severity and mortality. Lower dosing of PTCy also was associated with less broad reductions of T-cell numbers after PTCy and lower toxicity than higher dosing.
In patients on an NIH study using myeloablative conditioning, a dose of 25 mg/kg/day has been associated with more rapid engraftment and potentially better immune function without an increase in severe acute GVHD.
Objectives:
Determine whether PTCy 25 mg/kg on days +3 and +4 can maintain adequate protection against grade III-IV acute GVHD and reduce toxicity associated with transplantation in older and/or unfit transplant recipients receiving reduced intensity conditioned allogeneic HCT.
Determine the frailty measures associated with outcomes after allogeneic transplantation.
Eligibility:
Histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation.
Age 60-85 years, or age 18-60 years and unfit for myeloablative conditioning (MAC).
At least one potentially suitable HLA-matched related, HLA-haploidentical donor, HLA-matched unrelated, or >=5/10 HLA-mismatched unrelated donor.
Karnofsky performance score >=60
Adequate organ function
Design:
Open-label, multi-center, non-randomized, phase I/II study
There will be four separate arms: HLA-matched elderly, HLA-matched young/infirm, HLA-partially matched elderly, and HLA-partially matched young/infirm
All subjects will receive nonmyeloablative conditioning consisting of fludarabine, cyclophosphamide, and total body irradiation; GVHD prophylaxis with PTCy 25 mg/kg on days +3 and +4, MMF, and sirolimus; and bone marrow as the stem cell source
Subjects will be evaluated for development of grade III-IV acute GVHD (aGVHD) at day +60 as the dose-limiting toxicities for the Simon two-stage design. Dose escalation of PTCy will be permitted within each arm if stopping rules are met at the 25 mg/kg/day on days +3 and +4 dose.
Frailty assessments will be performed prior to transplantation conditioning and serially after allogeneic transplantation.
- Conditions
- Hematologic Neoplasms
- Being tested
- Mycophenolate Mofetil, Allogeneic HSCT, Fludarabine, Sirolimus, Filgrastim
- Keywords
- myeloablative conditioning, Chronic Graft-Versus-Host Disease, hematopoietic cell transplantation, Fludarabine, TOTAL BODY IRRADIATION
- Medical subject headings
- Hematologic Neoplasms, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism.
Allogeneic HSCTProcedure or surgery
Stem cell transplant
FludarabineDrug
30 mg/m2 IV infusion over 30-60 minutes once daily for 5 days (Pre-Transplant days -6 through -2).
SirolimusDrug
Loading dose of 6 mg orally given on day +5 (calculated based on actual body weight, max 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 +60 with no taper. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism.
FilgrastimDrug
begins on day +5 at a dose of 5 mcg/kg/day (actual body weight) IV or subcutaneously, until the absolute neutrophil count is > 1,000/mm3 over the course of three days or > 5,000/mm3 on one day. Rounding to the nearest vial is allowed. G-CSF may be stopped early or not administered if required by the clinical circumstance. Additional G-CSF may be administered as warranted.
CyclophosphamideDrug
Pre-transplant: 14.5 mg/kg/day IV daily for 2 days pre-transplant (Pre-Transplant days -6 and -5). Post-transplant: 25 mg/kg/day or 35 mg/kg/day (Post-transplant days +3 and +4).
MesnaDrug
25 or 35 mg/kg (equal to the cyclophosphamide dose) as IV infusion concomitant with cyclophosphamide. Mesna may or may not be given with the pre-transplant cyclophosphamide depending on institutional practice.
Total Body Irradiation (TBI)Procedure or surgery
400 centigray (cGy) to be delivered in 2 fractions as 200 cGy per fraction twice daily. Pre-Transplant Day -1 (or Day 0 prior to graft administration)
| Study group | Role | What they receive |
|---|---|---|
| Donors | No intervention | Collection of research samples on bone marrow donors |
| Older, HLA-matched | Experimental | Subjects age 60-85 with hematologic malignancies and an HLA-matched related or unrelated donor Receives: Drug: Mycophenolate Mofetil; Procedure: Allogeneic HSCT; Drug: Fludarabine; Drug: Sirolimus; Drug: Filgrastim; Drug: Cyclophosphamide; Drug: Mesna; Procedure: Total Body Irradiation (TBI) |
| Older, HLA-mismatched | Experimental | Subjects age 60-85 with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor Receives: Drug: Mycophenolate Mofetil; Procedure: Allogeneic HSCT; Drug: Fludarabine; Drug: Sirolimus; Drug: Filgrastim; Drug: Cyclophosphamide; Drug: Mesna; Procedure: Total Body Irradiation (TBI) |
| Younger, HLA-matched | Experimental | Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-matched related or unrelated donor Receives: Drug: Mycophenolate Mofetil; Procedure: Allogeneic HSCT; Drug: Fludarabine; Drug: Sirolimus; Drug: Filgrastim; Drug: Cyclophosphamide; Drug: Mesna; Procedure: Total Body Irradiation (TBI) |
| Younger, HLA-mismatched | Experimental | Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor Receives: Drug: Mycophenolate Mofetil; Procedure: Allogeneic HSCT; Drug: Fludarabine; Drug: Sirolimus; Drug: Filgrastim; Drug: Cyclophosphamide; Drug: Mesna; Procedure: Total Body Irradiation (TBI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
determine if optimal dose of PTCy to prevent grade III-IV acute GVHD (aGVHD) at day +60
The fraction of evaluable patients who experience grade III-IV aGVHD at day +60 will be determined and reported along with 80% and 95% two-sided confidence intervals. In addition, a cumulative incidence curve for this endpoint will be constructed.
Measured: 60 days
Secondary outcomes (8)
Grade III-IV acute GVHD at day 100 and 200
Estimates will be determined using competing risk-based cumulative incidence curves. Graft failure, relapse, donor lymphocyte infusion, non-relapse mortality, and chronic GVHD will be competing risks for acute GVHD. Grade III-IV aGVHD also will be evaluated descriptively including fractions who attain each condition at day 100 and 200 days, and 95% confidence intervals.
Measured: 100 days/200 days
Grade II-IV acute GVHD at day 100 and 200
Estimates will be determined using competing risk-based cumulative incidence curves. Grade II-IV aGVHD also will be evaluated descriptively including fractions who attain each condition at day 100 and 200 days, and 95% confidence intervals.
Measured: 100 days/200 days
Rate of Fried s Frailty Phenotypes (FP)
Frequency of different phenotypes
Measured: 1 year
Chronic GVHD at one year
Estimates will be determined using competing risk-based cumulative incidence curves. Graft failure, relapse, donor lymphocyte infusion, and non-relapse mortality will be competing risks for chronic GVHD.
Measured: 1 year
Progression/relapse at one year
Estimates will be determined using Kaplan-Meier curves. Relapse and non-relapse mortality will be competing risks for each other.
Measured: 1 year
Non-relapse mortality at 100 days and one year
Estimates will be determined using competing risk-based cumulative incidence curves. Relapse and non-relapse mortality will be competing risks for each other.
Measured: 100 days and 1 year
Overall survival, progression-free survival, and disease-free survival at one year
Estimates will be determined using Kaplan-Meier curves.
Measured: 1 year
Estimation of platelet engraftment, neutrophil engraftment.
Rate and timing will be evaluated descriptively, including fractions who attain each condition at day 28 and 100, along with 95% confidence intervals. Ranges and medians will be calculated only in engrafting participants.
Measured: day 28 and day 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2021
- Study start23 Sep 2021
- Primary completion27 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christopher G Kanakry, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04959175
- Sponsor's protocol ID
- 10000359
- Other IDs
- 000359-C
- Status last verified
- 13 Oct 2026
- First submitted
- 10 Jul 2021
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study to Reduce Post-transplantation Cyclophosphamide Dosing for Older or Unfit Patients Undergoing Bone Marrow Transplantation for Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT04959175
- Acronym / sponsor ID
- 10000359
- Conditions
- Hematologic Neoplasms
- Keywords
- myeloablative conditioning, Chronic Graft-Versus-Host Disease, hematopoietic cell transplantation, Fludarabine, TOTAL BODY IRRADIATION
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 23 Sep 2021 (actual)
- Primary completion
- 27 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 13 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Certain blood cancers can be treated with blood or bone marrow transplants. Sometimes the donor cells attack the recipient's body, called graft-versus-host disease (GVHD). The chemotherapy drug cyclophosphamide helps reduce the risk and severity of GVHD. Researchers want to learn if using a lower dose of cyclophosphamide may reduce the drug's side effects while maintaining its effectiveness. Such an approach is being used in an ongoing clinical study at the NIH with promising results, but this approach has not been tested for transplants using lower doses of chemotherapy/radiation prior to the transplant.
Objective:
To learn if using a lower dose of cyclophosphamide will help people have a successful transplant and have fewer problems and side effects.
Eligibility:
Adults ages 18-85 who have a blood cancer that did not respond well to standard treatments or is at high risk for relapse without transplant, and their donors.
Design:
Participants may be screened with the following:
Medical history
Physical exam
Blood and urine tests
Heart and lung tests
Body imaging scans (they may get a contrast agent)
Spinal tap
Bone marrow biopsy
Participants will be hospitalized for 4-6 weeks. They will have a central venous catheter placed in a chest or neck vein. It will be used to give medicines, transfusions, and the donor cells, and to take blood. In the week before transplant, they will get 2 chemotherapy drugs and radiation. After the transplant, they will get the study drug for 2 days. They will take other drugs for up to 2 months.
Participants must stay near NIH for 3 months after discharge for weekly study visits. Then they will have visits every 3-12 months until 5 years after transplant.
Participants and donors will give blood, bone marrow, saliva, cheek swab, urine, and stool samples for research.
Detailed description
Background:
With novel therapies for hematologic malignancies, an increasing number of older and/or less fit patients are achieving remissions, but these new therapies are not curative, making consolidation approaches with curative intent such as allogeneic transplantation necessary.
Frailty is a phenotype that predicts a patient s intolerance of physiologic stressors and may predict a patient s tolerance of intensive consolidative strategies.
Frailty phenotype, though increasing in incidence in older patients, can occur in younger patients and may predict poor survival after allogeneic transplantation.
We have yet to define the ideal allogeneic transplantation regimen for older patients or those with frailty or pre-frail phenotypes.
Post-transplantation cyclophosphamide (PTCy) reduces rates of severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) and safely facilitates human leukocyte antigen (HLA)-matched-related, HLA-matched-unrelated, HLA-mismatched-unrelated, and HLA-haploidentical HCT; it has become the most widely adopted change to transplantation platforms over the last decade.
When clinically translated, the dose (50 mg/kg/day) of PTCy used was partly extrapolated from murine major histocompatibility complex (MHC)-matched skin allografting models and was partly empirical.
In both MHC-haploidentical and MHC-disparate murine HCT models, a dose of 25 mg/kg/day was superior to 50 mg/kg/day on days +3 and +4 in terms of GVHD severity and mortality. Lower dosing of PTCy also was associated with less broad reductions of T-cell numbers after PTCy and lower toxicity than higher dosing.
In patients on an NIH study using myeloablative conditioning, a dose of 25 mg/kg/day has been associated with more rapid engraftment and potentially better immune function without an increase in severe acute GVHD.
Objectives:
Determine whether PTCy 25 mg/kg on days +3 and +4 can maintain adequate protection against grade III-IV acute GVHD and reduce toxicity associated with transplantation in older and/or unfit transplant recipients receiving reduced intensity conditioned allogeneic HCT.
Determine the frailty measures associated with outcomes after allogeneic transplantation.
Eligibility:
Histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation.
Age 60-85 years, or age 18-60 years and unfit for myeloablative conditioning (MAC).
At least one potentially suitable HLA-matched related, HLA-haploidentical donor, HLA-matched unrelated, or >=5/10 HLA-mismatched unrelated donor.
Karnofsky performance score >=60
Adequate organ function
Design:
Open-label, multi-center, non-randomized, phase I/II study
There will be four separate arms: HLA-matched elderly, HLA-matched young/infirm, HLA-partially matched elderly, and HLA-partially matched young/infirm
All subjects will receive nonmyeloablative conditioning consisting of fludarabine, cyclophosphamide, and total body irradiation; GVHD prophylaxis with PTCy 25 mg/kg on days +3 and +4, MMF, and sirolimus; and bone marrow as the stem cell source
Subjects will be evaluated for development of grade III-IV acute GVHD (aGVHD) at day +60 as the dose-limiting toxicities for the Simon two-stage design. Dose escalation of PTCy will be permitted within each arm if stopping rules are met at the 25 mg/kg/day on days +3 and +4 dose.
Frailty assessments will be performed prior to transplantation conditioning and serially after allogeneic transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Donors | No intervention | –Collection of research samples on bone marrow donors |
| Older, HLA-matched | Experimental | Drug: Mycophenolate Mofetil, Procedure: Allogeneic HSCT, Drug: Fludarabine, Drug: Sirolimus, Drug: Filgrastim, Drug: Cyclophosphamide, Drug: Mesna, Procedure: Total Body Irradiation (TBI)Subjects age 60-85 with hematologic malignancies and an HLA-matched related or unrelated donor |
| Older, HLA-mismatched | Experimental | Drug: Mycophenolate Mofetil, Procedure: Allogeneic HSCT, Drug: Fludarabine, Drug: Sirolimus, Drug: Filgrastim, Drug: Cyclophosphamide, Drug: Mesna, Procedure: Total Body Irradiation (TBI)Subjects age 60-85 with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor |
| Younger, HLA-matched | Experimental | Drug: Mycophenolate Mofetil, Procedure: Allogeneic HSCT, Drug: Fludarabine, Drug: Sirolimus, Drug: Filgrastim, Drug: Cyclophosphamide, Drug: Mesna, Procedure: Total Body Irradiation (TBI)Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-matched related or unrelated donor |
| Younger, HLA-mismatched | Experimental | Drug: Mycophenolate Mofetil, Procedure: Allogeneic HSCT, Drug: Fludarabine, Drug: Sirolimus, Drug: Filgrastim, Drug: Cyclophosphamide, Drug: Mesna, Procedure: Total Body Irradiation (TBI)Subjects age 18-60 unfit for MAC with hematologic malignancies and an HLA-haploidentical or HLA-mismatched unrelated donor |
Who may qualify
- Ages
- 12 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Related (age >=12) and unrelated (age >=18) donors deemed eligible (i.e., evaluated at NIH in accordance with existing institutional Standard Policies and Procedures or evaluated per the standards required by the IRB of the National Marrow Donor Program or applicable registry), and willing to donate research samples will be included.
Key exclusion criteria (8 listed)
- Subjects who are receiving any other investigational agents. Prior experimental therapies must have been completed at least 2 weeks prior to the date of beginning conditioning.
- Poorly controlled malignant indication for transplantation such as:
- Uncontrolled intercurrent illness that in the opinion of the site PI would make it unsafe to proceed with transplantation.
- The potential for some of the study medications to be transmissible via breast milk of nursing mothers is unknown. Because there is unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued.
- Active malignancy of non-hematopoietic type which is: metastatic, relapsed/refractory to treatment, or locally advanced and not amenable to curative treatment, or limited disease treated with curative intent treatment within the last 2 years. This excludes nonmelanoma skin cancers.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate Mofetil15 mg/kg orally or IV three times daily (max 1000 mg/dose) starting on day +5, continued through day +35. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism. | Drug | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
| Allogeneic HSCTStem cell transplant | Procedure or surgery | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
| Fludarabine30 mg/m2 IV infusion over 30-60 minutes once daily for 5 days (Pre-Transplant days -6 through -2). | Drug | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
| SirolimusLoading dose of 6 mg orally given on day +5 (calculated based on actual body weight, max 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 +60 with no taper. May be continued beyond the protocol specified stop date if there is GVHD or mixed chimerism. | Drug | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
| Filgrastimbegins on day +5 at a dose of 5 mcg/kg/day (actual body weight) IV or subcutaneously, until the absolute neutrophil count is > 1,000/mm3 over the course of three days or > 5,000/mm3 on one day. Rounding to the nearest vial is allowed. G-CSF may be stopped early or not administered if required by the clinical circumstance. Additional G-CSF may be administered as warranted. | Drug | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
| CyclophosphamidePre-transplant: 14.5 mg/kg/day IV daily for 2 days pre-transplant (Pre-Transplant days -6 and -5). Post-transplant: 25 mg/kg/day or 35 mg/kg/day (Post-transplant days +3 and +4). | Drug | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
| Mesna25 or 35 mg/kg (equal to the cyclophosphamide dose) as IV infusion concomitant with cyclophosphamide. Mesna may or may not be given with the pre-transplant cyclophosphamide depending on institutional practice. | Drug | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
| Total Body Irradiation (TBI)400 centigray (cGy) to be delivered in 2 fractions as 200 cGy per fraction twice daily. Pre-Transplant Day -1 (or Day 0 prior to graft administration) | Procedure or surgery | Older, HLA-matched, Older, HLA-mismatched, Younger, HLA-matched, Younger, HLA-mismatched |
Primary outcome
determine if optimal dose of PTCy to prevent grade III-IV acute GVHD (aGVHD) at day +60
Time frame: 60 days
The fraction of evaluable patients who experience grade III-IV aGVHD at day +60 will be determined and reported along with 80% and 95% two-sided confidence intervals. In addition, a cumulative incidence curve for this endpoint will be constructed.
8 secondary outcomes
Grade III-IV acute GVHD at day 100 and 200
Time frame: 100 days/200 days
Grade II-IV acute GVHD at day 100 and 200
Time frame: 100 days/200 days
Rate of Fried s Frailty Phenotypes (FP)
Time frame: 1 year
Chronic GVHD at one year
Time frame: 1 year
Progression/relapse at one year
Time frame: 1 year
Non-relapse mortality at 100 days and one year
Time frame: 100 days and 1 year
Overall survival, progression-free survival, and disease-free survival at one year
Time frame: 1 year
Estimation of platelet engraftment, neutrophil engraftment.
Time frame: day 28 and day 100
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Acute Lymphoblastic Leukemia, B-All
RecruitingPhase 1/2
A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Daratumumab, and Dexamethasone Plus Pomalidomide in Multiple Myeloma
Relapsed/Refractory Multiple Myeloma
RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christopher G Kanakry, M.D. principal investigator
National Cancer Institute (NCI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mycophenolate Mofetil, Allogeneic HSCT and Fludarabine in people with Hematologic Neoplasms, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amy H Chai ((240) 858-3755, amy.chai@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
determine if optimal dose of PTCy to prevent grade III-IV acute GVHD (aGVHD) at day +60 (time frame: 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.