Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

NCT03333486 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: I 40916NCI-2017-01949
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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, 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.

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; Aplastic Anemia; B-Cell Non-Hodgkin Lymphoma; CD40 Ligand Deficiency; Chronic Granulomatous Disease; Chronic Leukemia in Remission; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Congenital Amegakaryocytic Thrombocytopenia; Congenital Neutropenia; Congenital Pure Red Cell Aplasia; Glanzmann Thrombasthenia; Immunodeficiency Syndrome; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Paroxysmal Nocturnal Hemoglobinuria; Plasma Cell Myeloma; Polycythemia Vera; Recurrent Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Severe Aplastic Anemia; Shwachman-Diamond Syndrome; Sickle Cell Disease; T-Cell Non-Hodgkin Lymphoma; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

Outcome Measures

Primary Outcomes (1)

• Relapse Rate

  The number of participants that relapse within 1 year.

  At 1 year

Secondary Outcomes (7)

• ANC Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment

  At 1 year post-transplant

• Platelet Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment

  At 1 year post-transplant

• Proportion of Participants With Acute Graft Versus Host Disease (GVHD)

  At 100 days post-transplant

• Proportion of Participants With Chronic Graft Versus Host Disease (GVHD)

  At 1 year post-transplant

• Overall Survival

  up to 5 years and 8 months

Other Outcomes (3)

• Immune Reconstitution

  Up to 1 year

• Lymphoid Chimerism Expressed as a Percentage of Donor Cells

  At 30 days

• Myeloid Chimerism Expressed as a Percentage of Donor Cells

  At 100 days

Study Arms (1)

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.

Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Total-Body Irradiation

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support, Peripheral Stem Cell Transplant, peripheral stem cell transplantation

Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

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; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic-Phase; Congenital amegakaryocytic thrombocytopenia; Neutropenia, Severe Congenital, Autosomal Recessive 3; Anemia, Diamond-Blackfan; Thrombasthenia; Immunologic Deficiency Syndromes; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Hemoglobinuria, Paroxysmal; Multiple Myeloma; Polycythemia Vera; Lymphoma, Non-Hodgkin; Shwachman-Diamond Syndrome; Anemia, Sickle Cell; Lymphoma, T-Cell; Thalassemia; Waldenstrom Macroglobulinemia; Wiskott-Aldrich Syndrome

Interventions

Cyclophosphamide; fludarabine phosphate; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Anemia; Bone Marrow Failure Disorders; Lymphoma; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, B-Cell; Myelodysplastic-Myeloproliferative Diseases; Anemia, Hypoplastic, Congenital; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Anemia, Hemolytic; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Exocrine Pancreatic Insufficiency; Pancreatic Diseases; Digestive System Diseases; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipomatosis; Anemia, Hemolytic, Congenital; Hemoglobinopathies; Lymphopenia; Leukopenia; Cytopenia; Primary Immunodeficiency Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

Adrienne.Groman@RoswellPark.org

716-845-2300

Study Officials

• Philip McCarthy, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 7, 2017
• Study Start: December 7, 2017
• Primary Completion: August 28, 2023
• Study Completion: August 28, 2023
• Last Updated: July 4, 2025
• Results First Posted: April 2, 2024

Record last verified: 2025-06

Locations

US (1)