A Phase 1/2 interventional study of Fludarabine and Cytoxan in Hematologic Malignancies, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Completed at 1 site in United States. Open to participants aged 6 Months to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-02-19.
Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Phase 1/2, Interventional, and Treatment
If transplantation using mismatched unrelated donors or non-first-degree relatives could be performed with an acceptable toxicity profile, an important unmet need would be served. Towards this goal, the current study extends our platform of nonmyeloablative, partially HLA-mismatched bone marrow transplant (BMT) and Peripheral Blood Stem Cell Transplant (PBSCT) to the use of such donors, investigating up to several postgrafting immunosuppression regimens that incorporate high-dose Cy. Of central interest is the incorporation of sirolimus into this postgrafting immunosuppression regimen.
The primary goal for phase 1 is to identify a transplant regimen associated with acceptable rates of severe acute GVHD and NRM by Day 100 and for phase 2 estimate the 6-month probability of survival without having had acute grade III- IV GVHD or graft failure.
1,464 studies on the registry are indexed under Hematologic Neoplasms; 433 are open to participants now.
This study's enrollment of 87 is above the median of 45 across 1,068 interventional studies indexed under Hematologic Neoplasms.
Browse Hematologic Neoplasms studies →Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 572 studies on the registry; 73 are open to participants now.
Of its 111 completed or terminated interventional studies of FDA-regulated products, 67 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patient Inclusion Criteria:
Eligible diagnoses:
Poor-risk acute leukemia in first remission, with remission defined as \<5% bone marrow blasts morphologically:
AML with at least one of the following:
ALL (leukemia and/or lymphoma) with at least one of the following:
MDS with at least one of the following poor-risk features:
Low-grade non-Hodgkin lymphoma (including SLL and CLL) or plasma cell neoplasm that has:
Poor-risk CLL or SLL as follows:
Aggressive non-Hodgkin lymphoma as follows, provided there is stable disease or better to last therapy:
Eligible subtypes of aggressive non-Hodgkin lymphoma include:
One of the following, in order to lower risk of graft rejection:
NOTE: Patients who have received treatment outside of these windows may be eligible if it is deemed sufficient to reduce graft rejection risk; this will be decided on a case-by-case basis by the PI or co-PI.
Adequate end-organ function as measured by:
Patient Exclusion Criteria:
No uncontrolled bacterial, viral, or fungal infection.
Donor Inclusion Criteria:
Potential donors consist of:
Donor Exclusion Criteria:
Pre-BMT : * Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV * Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV * Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction Day 0: Allogeneic blood or marrow transplantation (BMT) Post-Transplantation Immunosuppression Consisting of: * Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV * Day 5: Sirolimus loading dose 6 mg PO once * Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day) * Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
Drug: Fludarabine · Drug: Cytoxan · Radiation: Total Body Irradiation · Procedure: Allogeneic Blood or Marrow Transplant · Drug: Mycophenolate Mofetil · Drug: Sirolimus
Pre-BMT: * Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV * Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV * Day -1: 400 cGy TBI administered in a single fraction Day 0: BMT Post-Transplantation Immunosuppression Consisting of: * Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV * Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day) * Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD
Drug: Fludarabine · Drug: Cytoxan · Radiation: Total Body Irradiation · Procedure: Allogeneic Blood or Marrow Transplant · Drug: Mycophenolate Mofetil · Drug: Tacrolimus
Pre-PBSCT: * Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV * Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV * Day -1: 400 cGy TBI administered in a single fraction Day 0: Peripheral Blood Stem Cell Transplant (PBSCT) Post-Transplantation Immunosuppression Consisting of: * Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV * Day 5: Sirolimus loading dose 6 mg PO once * Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day) * Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
Drug: Fludarabine · Drug: Cytoxan · Radiation: Total Body Irradiation · Procedure: Peripheral Blood Stem Cell Transplant · Drug: Mycophenolate Mofetil · Drug: Sirolimus
Pre-PBSCT: * Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV * Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV * Day -1: 400 cGy TBI administered in a single fraction Day 0: Peripheral Blood Stem Cell Transplant (PBSCT) Post-Transplantation Immunosuppression Consisting of: * Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV * Day 5: Sirolimus loading dose 6 mg PO once * Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day) * Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
Drug: Fludarabine · Drug: Cytoxan · Radiation: Total Body Irradiation · Procedure: Peripheral Blood Stem Cell Transplant · Drug: Mycophenolate Mofetil · Drug: Sirolimus
Fludarabine 30 mg/m2/day
Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day
Also known as: High-dose Cytoxan
400 cGy TBI administered in a single fraction
Also known as: TBI
Also known as: BMT
Also known as: PBSCT
15mg/kg by mouth three times daily
Also known as: MMF
Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
Tacrolimus 1mg intravenously, daily
Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD)
Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable rates of severe acute GVHD (\< 25%).
Time frame: Study Day 100
Number of Participants Who Have Transplant-related Nonrelapse Mortality (NRM)
Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable number of participants with transplant-related NRM.
Time frame: Study Day 100
6-month Probability of Survival as Assessed by Absence of Grade III-IV GVHD or Evidence of Graft Failure.
Number of participants who do not have grade II-IV GVHD or evidence of graft failure will be assessed.
Time frame: 6 months
Progression-free Survival
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Time frame: 2 years
Event-free Survival
All patients will be tracked from Day 0 to date of first observed disease progression, or death from any cause, or last patient evaluation. Patients will be followed on study to identify instances of death, progression or disease recurrence.
Time frame: 7 years
Overall Survival
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Time frame: 7 years
Cumulative Incidence of Progression or Relapse
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
Time frame: 7 years
Cumulative Incidence of Non-relapse Mortality (NRM).
All patients will be tracked from Day 0 to date of first observed disease relapse or progression, or death from disease, or last patient evaluation. Patients who have not progressed or died by their last patient contact visit will be censored at the last date they were assessed and deemed free of relapse or progression.
Time frame: 7 years
Cumulative Incidence of Acute Grade II-IV GVHD.
All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.
Time frame: 1 year
Cumulative Incidence of Acute Grade III-IV GVHD
All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.
Time frame: 1 year
Cumulative Incidence of Chronic GVHD
All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.
Time frame: 1 year
Cumulative Incidence of Graft Failure
Number of cases with less than 5% donor chimerism in blood and/or bone marrow on \~Day 30 or after and on all subsequent measurements, in the absence of documented bone marrow involvement by malignancy.
Time frame: 1 year
Cumulative Incidence of Neutrophil Recovery
Number of cases who achieve a post nadir ANC greater or equal to 500/mm3 for three consecutive measurements on different days.
Time frame: 1 year
Cumulative Incidence of Platelet Recovery
Number of cases who achieve a platelet count greater than 20,000/mm3 or greater than 50,000/mm3 with no platelet transfusions in the preceding seven days, as measured as maintained on at least three consecutive measurements on different days.
Time frame: 1 year
Cumulative Incidence of Donor Engraftment
Number of cases who achieve either mixed donor chimerism is defined as greater than 5%, but less than 95%, donor or full donor chimerism is defined as \> 95% donor.
Time frame: 1 year
Cumulative Incidence of Failure Free Survival
Number of cases who reach the end of the trial without severe acute (grade III-IV) GVHD, graft failure, or non-relapse mortality
Time frame: 7 years
| Milestone | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Started | 54 | 1 | 30 | 2 |
| Completed | 54 | 1 | 30 | 2 |
| Not completed | 0 | 0 | 0 | 0 |
Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable rates of severe acute GVHD (\< 25%).
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD) | 2 | 0 | 5 | 1 |
Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable number of participants with transplant-related NRM.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Number of Participants Who Have Transplant-related Nonrelapse Mortality (NRM) | 2 | 0 | 1 | 0 |
Number of participants who do not have grade II-IV GVHD or evidence of graft failure will be assessed.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| 6-month Probability of Survival as Assessed by Absence of Grade III-IV GVHD or Evidence of Graft Failure. | 51 | 1 | 26 | 2 |
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Progression-free Survival | 48 | 1 | 30 | 2 |
All patients will be tracked from Day 0 to date of first observed disease progression, or death from any cause, or last patient evaluation. Patients will be followed on study to identify instances of death, progression or disease recurrence.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Event-free Survival | 47 | 1 | 26 | 2 |
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Overall Survival | 47 | 1 | 26 | 2 |
All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Progression or Relapse | 4 | 0 | 3 | 0 |
All patients will be tracked from Day 0 to date of first observed disease relapse or progression, or death from disease, or last patient evaluation. Patients who have not progressed or died by their last patient contact visit will be censored at the last date they were assessed and deemed free of relapse or progression.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Non-relapse Mortality (NRM). | 7 | 0 | 4 | 0 |
All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Acute Grade II-IV GVHD. | 2 | 0 | 1 | 0 |
All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Acute Grade III-IV GVHD | 0 | 0 | 0 | 0 |
All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Chronic GVHD | 0 | 0 | 0 | 0 |
Number of cases with less than 5% donor chimerism in blood and/or bone marrow on \~Day 30 or after and on all subsequent measurements, in the absence of documented bone marrow involvement by malignancy.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Graft Failure | 2 | 0 | 0 | 1 |
Number of cases who achieve a post nadir ANC greater or equal to 500/mm3 for three consecutive measurements on different days.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Neutrophil Recovery | 54 | 1 | 30 | 2 |
Number of cases who achieve a platelet count greater than 20,000/mm3 or greater than 50,000/mm3 with no platelet transfusions in the preceding seven days, as measured as maintained on at least three consecutive measurements on different days.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Platelet Recovery | 54 | 1 | 29 | 2 |
Number of cases who achieve either mixed donor chimerism is defined as greater than 5%, but less than 95%, donor or full donor chimerism is defined as \> 95% donor.
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Donor Engraftment | 53 | 1 | 30 | 2 |
Number of cases who reach the end of the trial without severe acute (grade III-IV) GVHD, graft failure, or non-relapse mortality
| Participants | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| Cumulative Incidence of Failure Free Survival | 53 | 1 | 30 | 2 |
Collected over From consent until 1 year after transplant. All-Cause mortality was collected for up to 7 years. Non-serious and serious adverse events were collected for up to 1 year after transplant.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| REGIMEN B | 2/54 (3.7%) | 1/54 (1.9%) | 1/54 (1.9%) |
| REGIMEN C | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| REGIMEN B2 | 1/30 (3.3%) | 0/30 (0%) | 0/30 (0%) |
| REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) |
| Event | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| ColitisGastrointestinal disorders | 1/54 | 0/1 | 0/30 | 0/2 |
| Event | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors |
|---|---|---|---|---|
| DiarrheaGastrointestinal disorders | 1/54 | 0/1 | 0/30 | 0/2 |
| Age, Categorical(Participants) | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors | Total |
|---|---|---|---|---|---|
| <=18 years | 2 | 0 | 0 | 0 | 2 |
| Between 18 and 65 years | 41 | 0 | 25 | 2 | 68 |
| >=65 years | 11 | 1 | 5 | 0 | 17 |
| Age, Continuous(years) | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors | Total |
|---|---|---|---|---|---|
| Mean | 53 ± 13.74 | 65 ± 0.00 | 51 ± 13.09 | 54 ± 2.49 | 53 ± 13.37 |
| Sex: Female, Male(Participants) | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors | Total |
|---|---|---|---|---|---|
| Female | 22 | 0 | 16 | 0 | 38 |
| Male | 32 | 1 | 14 | 2 | 49 |
| Race and Ethnicity Not Collected(Participants) | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors | Total |
|---|---|---|---|---|---|
| Count of participants | — | — | — | — | 0 |
| Region of Enrollment(Participants) | REGIMEN B | REGIMEN C | REGIMEN B2 | REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors | Total |
|---|---|---|---|---|---|
| United States | 54 | 1 | 30 | 2 | 87 |
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins