Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 2NCT03333486
Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
A Phase 2 study testing Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Leukemia in Remission, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
This phase II trial studies how well fludarabine phosphate, cyclophosphamide, total body irradiation, and donor stem cell transplant work in treating patients with blood cancer. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells… Read more about this study
- Who is it for?
- Ages 1 year to 75 years
- Conditions the study is for
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Leukemia in Remission, Acute Lymphoblastic Leukemia
- What is being tested?
- Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2017to 28 Aug 2023
- Phase
- Phase 2
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 1 year to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Any disease that is considered transplant eligible per TCT standards
- Disease response noted (i.e. CR, non-CR, or not applicable): Assessed as per disease specific criteria
- Suitable related haploidentical donor identified per transplant service:
- Recipient should not have HLA antibodies to potential donor. If the recipient does have HLA antibodies to the potential donor, an alternative donor is preferred; however, if there are no suitable alternative donors, the anti-HLAt antibodies should be depleted per transplant service guidelines.
- Haploidentical donors that are ABO compatible with the recipient are preferred. Minor ABO incompatibility is preferred to major ABO incompatibility. Major ABO incompatibility between recipient and donor is the least preferred but still acceptable for this study.
- It is preferred that the haploidentical donor must be available to donate on day -1 and day 0, so that fresh product can be processed by the Stem Cell lab and administered to the patient on day 0.While less preferable, cryopreserved product may be utilized with this product.
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- Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation
- Left ventricular ejection fraction > 40%
- Bilirubin, liver alkaline phosphatase, serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
- Calculated creatinine clearance > 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics
- Have a Karnofsky (adult) or Lansky (for =< 16 years) performance status >= 60%
- Patient must be able to pass radiation evaluation (i.e.: able to receive 200 cGy)
- Patients who have failed a prior autologous transplant are eligible; however, at least 90 days must have elapsed between the start of this reduced intensity conditioning regimen and the last transplant if patient had a prior autologous BMT
- Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Participant must understand the investigational nature of this study and sign an independent ethics committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
- If patient is planned to use a fully matched donor, patient is excluded from trial; patient must be planned to undergo a haploidentical matched transplant to participate on study. Patient is still eligible for trial regardless of donor options if PI feels that haplo transplant is in the patient's best interest per clinical decision
Who cannot join
- Participants who have had chemotherapy (not including molecularly targeted agents; examples include, but are not limited to, tyrosine kinase inhibitors such as FLT3 inhibitors and IDH2 inhibitors), radiation treatment and/or surgery 7 days prior to starting conditioning regimen. Those who have not recovered sufficiently from adverse events due to agents administered more than 2 weeks earlier are also ineligible. Exceptions may be made on a case-by-case basis after discussion with the PI
- Uncontrolled central nervous system (CNS) disease (for hematologic malignancies) Per PI discretion
- Child-Pugh class B and C liver failure
- Concomitant active malignancy that would be expected to require chemotherapy within 3 years of transplant (other than non-melanoma skin cancer) Exception would include any concurrently existing malignancy that could be treated with a transplant per PI discretion (Example: Patient has AML but a history of mastocytosis)
- Patients who have received maximally allowed doses (given in 2 Gy fractionations, or equivalent) of previous radiation therapy to various organs; patients who previously have received a higher than allowed dose of radiation to a small lung, liver and brain volume, will be evaluated by the radiation oncologist to determine if the patient is eligible for study
- Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
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- Known human immunodeficiency virus (HIV) positive
- Pregnant or nursing female participants
- Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening
- Patients with donor specific HLA antibodies with a titer greater than 3000 MFI (whether or not they have undergone a desensitization protocol)
- Patients who have undergone a prior allogeneic hematopoietic or (other organ) transplant
- Treating physician considers the potential HLA haploidentical donor to be ineligible to receive G-CSF, and/or concern on the part of the treating physician for risk of harm to the potential donor with administration of G-CSF, and/or refusal by the potential donor (or donor's guardian) to receive G-CSF
- Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
- Received an investigational agent within 14 days prior to enrollment. Exceptions may be made on a case-by-case basis after discussion with PI
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: A Phase II Trial of Haploidentical Allogeneic Stem Cell Transplantation Utilizing Mobilized Peripheral Blood Stem Cells
This phase II trial studies how well fludarabine phosphate, cyclophosphamide, total body irradiation, and donor stem cell transplant work in treating patients with blood cancer. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also 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. The donated stem cells may also replace the patient?s immune cells and help destroy any remaining cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the rate of relapse, defined as recurrence of underlying disease or progression of underlying disease, at 1 year in patients who receive haploidentical peripheral blood stem cells (PBSCs) after reduced intensity conditioning and post-transplant cyclophosphamide and tocilizumab (or tocilizumab alternative).
SECONDARY OBJECTIVES:
- To evaluate safety including development of acute graft versus host disease (GVHD) and death at 100 days post-transplant, as well as other treatment related toxicities including chronic GVHD, engraftment rate, non-relapse mortality, progression free survival (PFS) at one year, and overall survival (OS) at one year, as compared with historical controls.
TERTIARY OBJECTIVES:
- Correlative studies will include chimerism analysis by molecular analysis and evaluation of immune reconstitution by cytomegalovirus (CMV) dextramer analysis using flow cytometry.
OUTLINE:
Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -6 to -2 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients undergo total body irradiation (TBI) on days -1 and peripheral blood stem cell transplantation (PBSCT) on day 0.
After completion of study treatment, patients are followed up at 30 and 100 days.
- Conditions
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Leukemia in Remission, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia With FLT3/ITD Mutation, Acute Myeloid Leukemia With Gene Mutations
- Being tested
- Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Peripheral Blood Stem Cell Transplantation, Total-Body Irradiation
- Medical subject headings
- Leukemia, Myeloid, Accelerated Phase, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Anemia, Aplastic, Lymphoma, B-Cell, Granulomatous Disease, Chronic, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support
Undergo PBSCT
Total-Body IrradiationRadiation
Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation
Undergo TBI
| Study group | Role | What they receive |
|---|---|---|
| Treatment (fludarabine, cyclophosphamide, TBI, PBSCT) | Experimental | Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients undergo TBI on days -1 and PBSCT on day 0. Receives: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Total-Body Irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relapse Rate
The number of participants that relapse within 1 year.
Measured: At 1 year
Secondary outcomes (7)
ANC Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment
Absolute Neutrophil Count Engraftment rate was defined as the number of participants that received an engraftment within 1 year post-transplant and ANC > 0.5x10^9/L for three consecutive days, out of the total number of participants. The rate was computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
Measured: At 1 year post-transplant
Platelet Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment
Platelet Engraftment rate was defined as the number of participants that received an engraftment within 1 year post-transplant and the platelets >= 20 x 10^9/L after 7 consecutive days with no platelet transfusions, out of the total number of participants. The rate was computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
Measured: At 1 year post-transplant
Proportion of Participants With Acute Graft Versus Host Disease (GVHD)
Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
Measured: At 100 days post-transplant
Proportion of Participants With Chronic Graft Versus Host Disease (GVHD)
Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
Measured: At 1 year post-transplant
Overall Survival
Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson. Will be obtained using the product-limit based Kaplan-Meier method.
Measured: up to 5 years and 8 months
Progression Free Survival
Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson. Will be obtained using the product-limit based Kaplan-Meier method.
Measured: up to 5 years and 8 months
Transplant Related Mortality
Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
Measured: At 1 year post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start7 Dec 2017
- Primary completion28 Aug 2023
- Study completion28 Aug 2023
Why it stopped: Futility analysis determined closure
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 Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveStudies 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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philip McCarthy, MD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333486
- Sponsor's protocol ID
- I 40916
- Other IDs
- NCI-2017-01949, I 40916
- Status last verified
- Jun 2025
- First submitted
- 2 Nov 2017
- Last updated
- 4 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No