A Phase 2 interventional study of Cyclophosphamide and Fludarabine in Sickle Cell Disease, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Terminated at 1 site in United States. Open to participants aged 2 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-04-17.
Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Phase 2, Interventional, and Treatment
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving sirolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by a donor bone marrow transplant works in treating patients with sickle cell anemia and other blood disorders.
OBJECTIVES:
OUTLINE:
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.
This study's enrollment of 43 is close to the median of 40 across 750 interventional studies indexed under Anemia, Sickle Cell.
Browse Anemia, Sickle Cell 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.
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following sickle cell anemias (Hb SS):
Meets 1 of the following criteria:
Partially mismatched (at least haploidentical) first-degree relative donor available
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Conditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 200. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.
Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Mycophenolate mofetil · Drug: Sirolimus · Procedure: Allogeneic bone marrow transplant · Radiation: Total body irradiation - 200 · Drug: Levetiracetam · Biological: Anti-thymocyte globulin
Conditioning regimen with anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation - 400. Seizure prophylaxis with levetiracetam. Allogeneic bone marrow transplant infusion on Day 0. Graft-vs-host-disease (GVHD) prophylaxis with cyclophosphamide, mycophenolate mofetil, and sirolimus.
Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Mycophenolate mofetil · Drug: Sirolimus · Procedure: Allogeneic bone marrow transplant · Drug: Levetiracetam · Biological: Anti-thymocyte globulin · Radiation: Total body irradiation - 400
Cyclophosphamide (Cy) 14.5 mg/kg/day intravenously (IV) on Days -6 and -5 and 50 mg/kg/day IV on Days +3 and +4.
Also known as: Cytoxan, Cy, CTX
Fludarabine 30 mg/m\^2/day IV on Days -6, -5, -4, -3, and -2.
Also known as: Fludara
Mycophenolate mofetil 15 mg/kg by mouth (PO) three times a day from Day +5 to Day +35.
Also known as: MMF, CellCept
The first dose of Sirolimus is 6 mg PO on Day +5. Further dosing is adjusted according to drug levels. Sirolimus is continued through Day +365.
Also known as: Rapamune
An allogeneic bone marrow transplant is a procedure that involves taking bone marrow from a donor and giving it to a recipient.
Also known as: Allo BMT
200 centigray (cGy) in one fraction on Day -1.
Also known as: TBI
Given at 500 mg PO twice daily from Day -6 to Day +365.
Also known as: Keppra
Test dose of 0.5 mg/kg IV given on Day -9, then 2 mg/kg/day IV on Day -8 and -7.
Also known as: ATG, Thymoglobulin
400 centigray (cGy) in one fraction on Day -1.
Also known as: TBI
Transplant-related Mortality
Number of participants who died for reasons related to bone marrow transplant.
Time frame: Up to one year
Progression-free Survival
Percentage of participants who are alive without relapse.
Time frame: 2 years
Donor Chimerism at 30 Days
Number of participants with full (95-100%), mixed (5-94%), and no (0-4%) donor cells. Chimerism is reported for unsorted whole blood and T cells.
Time frame: 30 days
Donor Chimerism at 1 Year
Number of participants with full (95-100%), mixed (5-94%), and no (0-4%) donor cells. Chimerism is reported for unsorted whole blood and T cells.
Time frame: 1 year
| Milestone | Transplant - 200 cGy | Transplant - 400 cGy |
|---|---|---|
| Started | 29 | 13 |
| Completed | 29 | 13 |
| Not completed | 0 | 0 |
Number of participants who died for reasons related to bone marrow transplant.
| Participants | Transplant - 200 cGy | Transplant - 400 cGy |
|---|---|---|
| Transplant-related Mortality | 1 | 0 |
Percentage of participants who are alive without relapse.
No measurements were reported for this outcome.
Number of participants with full (95-100%), mixed (5-94%), and no (0-4%) donor cells. Chimerism is reported for unsorted whole blood and T cells.
| Participants | Transplant - 200 cGy | Transplant - 400 cGy |
|---|---|---|
| Whole blood — 95-100% | 12 | 8 |
| Whole blood — 5-94% | 15 | 3 |
| Whole blood — 0-4% | 1 | 1 |
| Whole blood — Unknown or not measured | 1 | 1 |
| T cells — 95-100% | 4 | 4 |
| T cells — 5-94% | 18 | 8 |
| T cells — 0-4% | 5 | 0 |
| T cells — Unknown or not measured | 2 | 1 |
Number of participants with full (95-100%), mixed (5-94%), and no (0-4%) donor cells. Chimerism is reported for unsorted whole blood and T cells.
| Participants | Transplant - 200 cGy | Transplant - 400 cGy |
|---|---|---|
| Whole blood — 95-100% | 6 | 9 |
| Whole blood — 5-94% | 9 | 3 |
| Whole blood — 0-4% | 1 | 0 |
| Whole blood — Unknown or not measured | 13 | 1 |
| T cells — 95-100% | 7 | 10 |
| T cells — 5-94% | 9 | 2 |
| T cells — 0-4% | 0 | 0 |
| T cells — Unknown or not measured | 13 | 1 |
Collected over Up to 60 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Transplant - 200 cGy | 1/29 (3.4%) | 21/29 (72.4%) | 0/29 (0%) |
| Transplant - 400 cGy | 0/13 (0%) | 7/13 (53.8%) | 0/13 (0%) |
| Event | Transplant - 200 cGy | Transplant - 400 cGy |
|---|---|---|
| Febrile neutropeniaInfections and infestations | 8/29 | 5/13 |
| Vaso-occlusive crisisBlood and lymphatic system disorders | 10/29 | 0/13 |
| Acute kidney injuryRenal and urinary disorders | 5/29 | 0/13 |
| BacteremiaInfections and infestations | 4/29 | 0/13 |
| EmesisGastrointestinal disorders | 4/29 | 1/13 |
| FeverInfections and infestations | 4/29 | 0/13 |
| HeadacheGeneral disorders | 4/29 | 1/13 |
| Posterior reversible encephalopathy syndromeNervous system disorders | 4/29 | 0/13 |
| Pain - unspecifiedGeneral disorders | 3/29 | 0/13 |
| SeizureNervous system disorders | 3/29 | 0/13 |
| Age, Categorical(Participants) | Transplant - 200 cGy | Transplant - 400 cGy | Total |
|---|---|---|---|
| <=18 years | 9 | 6 | 15 |
| Between 18 and 65 years | 20 | 7 | 27 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Transplant - 200 cGy | Transplant - 400 cGy | Total |
|---|---|---|---|
| Median | 19 (6 to 42) | 21 (5 to 31) | 21 (5 to 42) |
| Sex: Female, Male(Participants) | Transplant - 200 cGy | Transplant - 400 cGy | Total |
|---|---|---|---|
| Female | 17 | 8 | 25 |
| Male | 12 | 5 | 17 |
| Ethnicity (NIH/OMB)(Participants) | Transplant - 200 cGy | Transplant - 400 cGy | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 29 | 13 | 42 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Transplant - 200 cGy | Transplant - 400 cGy | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 25 | 6 | 31 |
| White | 1 | 2 | 3 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 5 | 8 |
| Region of Enrollment(Participants) | Transplant - 200 cGy | Transplant - 400 cGy | Total |
|---|---|---|---|
| United States | 29 | 13 | 42 |
| Disease(Participants) | Transplant - 200 cGy | Transplant - 400 cGy | Total |
|---|---|---|---|
| Sickle cell disease | 25 | 7 | 32 |
| Thalassemia | 4 | 6 | 10 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
This study is terminated, as verified in Mar 2019. 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