Graft Versus Host DiseasePhase 2NCT02248597
Donor Stem Cell Transplant Followed by Cyclophosphamide in Treating Patients With Hematological Diseases
A Phase 2 study testing fludarabine phosphate, busulfan and cyclophosphamide in people with Graft Versus Host Disease and Hematopoietic/Lymphoid Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Graft Versus Host Disease, Hematopoietic/Lymphoid Cancer
- What is being tested?
- fludarabine phosphate, busulfan and cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2015to 18 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant consistent with the standard of care
- Remission of any acute hematologic malignancy or adequate disease control for chronic malignancies.
- Ages 18-69 years old.
- Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor
Who cannot join
- Significant organ dysfunction defined as: LV EF < 50% (evaluated by echocardiogram or MRI), DLCO or FEV1 < 65% predicted, AST/ALT > 2.5 x ULN, Bilirubin > 1.5 x ULN, Serum creatinine > 2mg/dL, dialysis, or prior renal transplant
- HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation)
- Positive pregnancy test for women of childbearing age.
- Major anticipated illness or organ failure incompatible with survival form transplant.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
Trial locations and contacts
1 site in 1 country.
United States1 site
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, 27157
About this study
Official title: Haploidentical Stem Cell Transplant Using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study
This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer 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 (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide results in 60% or better disease free survival (DFS) at 12 months at our institution.
SECONDARY OBJECTIVES:
- To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse mortality, and relapse.
OUTLINE:
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2
TRANSPLANT: Patients undergo stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35.
After completion of study treatment, patients are followed up periodically for 2 years.
- Being tested
- fludarabine phosphate, busulfan, cyclophosphamide, allogeneic hematopoietic stem cell transplantation, tacrolimus
- Medical subject headings
- Graft vs Host Disease, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called 2-F-ara-AMP, Beneflur, Fludara
Given IV
busulfanDrug
Also called BSF, BU, Misulfan, Mitosan
Given IV
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Undergo myeloablative or reduced intensity allogeneic stem cell transplant
tacrolimusDrug
Also called FK 506, Prograf
Also called Cellcept, MMF
| Study group | Role | What they receive |
|---|---|---|
| Treatment (stem cell transplant with GVHD prophylaxis) | Experimental | PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2
TRANSPLANT: Patients undergo stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation Receives: Drug: fludarabine phosphate; Drug: busulfan; Drug: cyclophosphamide; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: tacrolimus; Drug: mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
12 Month Disease Free Survival Probability
The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.
Measured: At 12 months
Secondary outcomes (4)
Rate of Acute GvHD
Kaplan-Meier estimation of the rate of acute GvHD in the study population at one year with a 95% confidence interval.
Measured: 12 months
Overall Survival
The survival function will be estimated and plotted using the method of Kaplan and Meier.
Measured: At 12 months
Progression Free Survival
Kaplan-Meier estimation of the percentage of patients who are alive without progressive disease at one year.
Measured: At 12 months
Relapse-free Mortality
Non-relapse mortality will be defined as time from registration to death due to anything other than relapse of hematological malignancy. Patients who relapse will be treated as a competing risk.
Measured: At 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study start25 Feb 2015
- Primary completion18 Jan 2022
- Study completion18 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Dianna S. Howard, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02248597
- Sponsor's protocol ID
- IRB00029210
- Other IDs
- NCI-2014-01898, CCCWFU 97214, P30CA012197
- Status last verified
- Oct 2023
- First submitted
- 23 Sep 2014
- Last updated
- 11 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haploidentical Stem Cell Transplant Using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study
- ClinicalTrials.gov ID
- NCT02248597
- Acronym / sponsor ID
- IRB00029210
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 Feb 2015 (actual)
- Primary completion
- 18 Jan 2022 (actual)
- Study completion
- 18 Jan 2023 (actual)
- First posted
- 25 Sep 2014 (estimated)
- Results
- Posted 11 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer 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 (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening.
Detailed description
PRIMARY OBJECTIVES:
- To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide results in 60% or better disease free survival (DFS) at 12 months at our institution.
SECONDARY OBJECTIVES:
- To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse mortality, and relapse.
OUTLINE:
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2
TRANSPLANT: Patients undergo stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35.
After completion of study treatment, patients are followed up periodically for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (stem cell transplant with GVHD prophylaxis) | Experimental | Drug: fludarabine phosphate, Drug: busulfan, Drug: cyclophosphamide, Procedure: allogeneic hematopoietic stem cell transplantation, Drug: tacrolimus, Drug: mycophenolate mofetilPREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2 TRANSPLANT: Patients undergo stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant consistent with the standard of care
- Remission of any acute hematologic malignancy or adequate disease control for chronic malignancies.
- Ages 18-69 years old.
- Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor
Key exclusion criteria (5 listed)
- Significant organ dysfunction defined as: LV EF < 50% (evaluated by echocardiogram or MRI), DLCO or FEV1 < 65% predicted, AST/ALT > 2.5 x ULN, Bilirubin > 1.5 x ULN, Serum creatinine > 2mg/dL, dialysis, or prior renal transplant
- HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation)
- Positive pregnancy test for women of childbearing age.
- Major anticipated illness or organ failure incompatible with survival form transplant.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
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 |
|---|---|---|
| fludarabine phosphateAlso: 2-F-ara-AMP, Beneflur, FludaraGiven IV | Drug | Treatment (stem cell transplant with GVHD prophylaxis) |
| busulfanAlso: BSF, BU, Misulfan, MitosanGiven IV | Drug | Treatment (stem cell transplant with GVHD prophylaxis) |
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Treatment (stem cell transplant with GVHD prophylaxis) |
| allogeneic hematopoietic stem cell transplantationUndergo myeloablative or reduced intensity allogeneic stem cell transplant | Procedure or surgery | Treatment (stem cell transplant with GVHD prophylaxis) |
| tacrolimusAlso: FK 506, Prograf | Drug | Treatment (stem cell transplant with GVHD prophylaxis) |
| mycophenolate mofetilAlso: Cellcept, MMF | Drug | Treatment (stem cell transplant with GVHD prophylaxis) |
Primary outcome
12 Month Disease Free Survival Probability
Time frame: At 12 months
The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.
4 secondary outcomes
Rate of Acute GvHD
Time frame: 12 months
Overall Survival
Time frame: At 12 months
Progression Free Survival
Time frame: At 12 months
Relapse-free Mortality
Time frame: At 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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. This study is not recruiting at the moment.
Dianna S. Howard principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing fludarabine phosphate, busulfan and cyclophosphamide in people with Graft Versus Host Disease and Hematopoietic/Lymphoid Cancer, run by Wake Forest University Health Sciences at 1 site 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 4 inclusion and 5 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: finished, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 11 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
12 Month Disease Free Survival Probability (time frame: At 12 months). 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 11 Oct 2023.