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Antineoplastic Agents

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All Drugs and Chemicals

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Cyclophosphamide

Fludarabine

Fludarabine phosphate

Cyclosporine

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Antitubercular Agents

filgrastim

graft-versus-tumor induction therapy

cyclophosphamide

cyclosporine

fludarabine phosphate

mycophenolate mofetil

umbilical cord blood transplantation

radiation therapy

Claudio G. Brunstein, MD, PhD

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving chemotherapy together with total-body irradiation followed by donor umbilical cord blood transplant, cyclosporine, and mycophenolate mofetil works in treating patients with hematologic cancer.

OBJECTIVES:

Primary

* Determine the engraftment potential of unrelated allogeneic umbilical cord blood (UCB) using nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with hematologic malignancies.

Secondary

* Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment in patients treated with this regimen.
* Determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients treated with this regimen.
* Determine the incidence of malignant relapse in patients treated with this regimen.
* Determine the 1- and 2-year survival and event-free survival of patients treated with this regimen.
* Determine the phenotype and function of immune cells recovering after UCB transplantation in patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to HLA disparity (0-1 vs 2) and number of graft units (1 vs 2).

* Nonmyeloablative conditioning: Patients receive nonmyeloablative conditioning comprising fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation twice daily on days -4 to -1.
* Unrelated allogeneic umbilical cord blood transplantation (UCBT): Patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
* Immunosuppression: Patients receive cyclosporine orally or IV over 2 hours 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper in the absence of graft-vs-host disease (GVHD). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 30, continuing beyond day 30 if no donor engraftment. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Chemotherapy and Total-Body Irradiation Followed by Donor Umbilical Cord Blood Transplant, Cyclosporine, and Mycophenolate Mofetil in Treating Patients With Hematologic Cancer

A Cyclophosphamide/Fludarabine/Total Body Irradiation Preparative Regimen for Patients With Hematological Malignancy Receiving Unrelated Donor Umbilical Cord Blood Transplantation

National Cancer Institute (NCI)

Masonic Cancer Center, University of Minnesota

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Myelodysplastic/myeloproliferative Disease

Participants will taken Fedratinib by mouth once a day every day of each 28 day cycle.

Participants will be given Fedratinib at a dose of 400 mg PO once daily (4-100 mg capsules). Fedratinib can be given at any time during the day, but patients are advised to take the dose at the same approximate time every day.

Fedratinib Pill

Quan Lovette

Andrew Kuykendall, MD

Onyee Chan, MD

Timothy E Kubal, MD, MBA

Jeffrey E Lancet, MD

Eric Padron, MD

David A Sallman, MD

Kendra L Sweet, MD

Keniya Chambers

Kristen Pettit, MD

Kaylie Sunyak

Abhay Singh, MD

The purpose of the study is to evaluate the effectiveness, safety, and tolerability of a study drug called fedratinib in participants with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) and chronic neutrophilic leukemia (CNL).

Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL)

A Phase 2 Study of Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL)

Patient's global impression of change will be measured using the validated questionnaire wherein patients are asked about the change in their myelofibrosis symptoms since starting on the study. Patients can choose from one of seven potential answers: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. This will be reportedly qualitatively wherein the number of patients choosing particular answers will be tabulated and frequencies will be reported.

Response rate of fedratinib in MDS/MPN and CNL. Investigators will measure the proportion of patients achieving a clinical response from baseline to week 24 as defined by Complete Response (CR), Partial Response (PR) or Clinical Benefit (CB) by modified MDS/MPN IWG Proposed response criteria.

Participants spleen size will be measured and compared to baseline spleen size measurement. Spleen response is defined as 50% reduction in palpable splenomegaly of a spleen that is at least 10cm at baseline, a spleen that is palpable at more than 5 cm at baseline becoming non-palpable, or, in cases where volumetric evaluation is feasible, a ≥ 35% reduction in spleen volume in patients with a baseline spleen volume \> 450 cc. Spleen responses by palpation will need to correlate with a 50% reduction in longest diameter of the spleen by imaging.

Reduction in MPN-SAF TSS score will be measured by comparing TSS score at day 84 assessment to TSS score on cycle 1 day 1. Only patients with baseline TSS ≥ 10 will be eligible for symptom response. Patients who do not have a TSS score performed at day 84 assessment or who have discontinued study drug prior to day 84 assessment will be considered to not have 50% reduction in TSS.

The MPN-SAF TSS is a questionnaire with nine items containing the most common symptoms reported by patients (concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss and fever), plus one item ("worst fatigue") from the "Brief Fatigue Inventory (BFI)". Each item has a score that ranges from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). A higher score therefore indicates more severe symptoms

Bristol-Myers Squibb

H. Lee Moffitt Cancer Center and Research Institute

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell, Marginal Zone

Hodgkin Disease

Polycythemia Vera

Polycythemia

Lymphoma, B-Cell

Thrombocytosis

Thrombocythemia, Essential

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Chronic Lymphocytic Leukemia

B-cell Lymphoma

Marginal Zone Lymphoma

Hodgkin Lymphoma

Essential Thrombocythemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Tipifarnib

Patients receive oral tipifarnib twice daily for 21 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 1 course of therapy, patients may receive subsequent therapy at the maximum tolerated dose at the investigator's discretion.

tipifarnib

Todd M. Zimmerman, MD

Randomized phase I trial to study the effectiveness of tipifarnib in treating patients who have advanced hematologic cancer. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

OBJECTIVES:

I. Determine the relationship between tipifarnib dose and inhibition of farnesylation in malignant cells of patients with advanced hematologic malignancies.

II. Determine the safety profile of this drug in this patient population. III. Determine the clinical activity of this drug in these patients.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 4 dose levels.

Patients receive oral tipifarnib twice daily for 21 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 1 course of therapy, patients may receive subsequent therapy at the maximum tolerated dose at the investigator's discretion.

Tipifarnib in Treating Patients With Advanced Hematologic Cancer

A Dose Finding Study of R115777 (NSC 702818) in Patients With Advanced Hematologic Malignancies

Patients receiving umbilical cord blood transplantation.

The graft will be given by slow injection into each posterior iliac crest.

John E. Wagner, MD

Rationale: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from the donor's umbilical cord blood are injected into the patient's bone marrow they may help make stem cells, red blood cells, white blood cells, and platelets.

Purpose: This phase I/II trial is studying the side effects of donor umbilical cord blood transplant when given directly into the bone marrow and to see how well it works in treating patients with hematologic cancer.

Objectives:

Primary

* Determine the safety, in terms of infusional toxicity, of myeloablative unrelated donor double-unit umbilical cord blood (UCB) transplantation via intra-bone marrow injection (IBMI) in patients with advanced or high-risk hematologic malignancy.
* Determine whether treatment with this regimen improves the time to neutrophil engraftment (compared to historical controls) in these patients.

Secondary

* Determine the incidence of sustained donor engraftment in patients treated with this regimen.
* Determine the relative contribution of each UCB unit to initial and sustained donor engraftment in these patients.
* Determine the incidence of grade II-IV and grade III-IV acute graft-vs-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
* Determine the incidence of day 100 and 180 transplant-related mortality in patients treated with this regimen.
* Determine the probability of survival at 100 days and 1 year post-transplantation in these patients.

Outline: This is a nonrandomized study.

Patients receive a myeloablative conditioning regimen. Patients also receive immunosuppression, growth factor, and supportive care as in protocol MT2005-10 (NCT00309842).

Patients receive 2 units of donor umbilical cord blood (UCB) by intra-bone marrow injection (IBMI) over 10 minutes each on day 0. If the IBMI procedure is not possible, then the UCB units are given intravenously (IV.)

After completion of study therapy, patients are followed periodically for 5 years.

Projected Accrual: A total of 36 patients will be accrued for this study.

Donor Umbilical Cord Blood Transplant By Injection Into the Bone Marrow in Treating Patients With Hematologic Cancer

A Phase I/II Study of Double Unit Umbilical Cord Blood (UCB) Transplantation Utilizing Graft Administration Via Intra-Bone Marrow Injection (Companion Protocol to MT2000-25)

Number of days to neutrophil recovery observed in recipients of two umbilical cord blood units (UCB)administered i.v. Neutrophil recovery is defined as first of 3 consecutive days with ANC (absolute neutrophil count) greater than or equal to 500/ul.

Number of patients with sustained neutrophil recovery with chimerism (evidence of engraftment of both cord blood transplants) at 6 months.

Number of patients who received both cord blood units and achieved sustained donor engraftment

Number of patients who exhibited grade II-IV acute GVHD at 100 days post umbilical cord blood transplant.

Number of patients who were deceased at days 100 and 180 from any cause other than relapse.

Overall survival of patients-Number of patients who were alive at Day 100 and 1 year post transplant.

Number of umbilical cord blood transplant patients developing severe GVHD at 100 days post transplant.

Number of umbilical cord blood transplant patients with limited and extensive chronic GVHD.

Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.

Umbilical Cord Blood Transplant Patients

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

This study was terminated early based on interim statistical analysis that indicated time to engraftment will not be improved compared to historical controls. While safe, lack of faster marrow recovery supports early discontinuation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy and Total-Body Irradiation Followed by Donor Umbilical Cord Blood Transplant, Cyclosporine, and Mycophenolate Mofetil in Treating Patients With Hematologic Cancer	NCT00290641	Chronic Myelopr... Leukemia Lymphoma Myelodysplastic...	filgrastim graft-versus-tu... cyclophosphamid... cyclosporine fludarabine pho... mycophenolate m... umbilical cord ... radiation thera...	- 45 Years	Masonic Cancer Center, University of Minnesota
Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL)	NCT05177211	Myeloproliferat... Chronic Neutrop... MDS	Fedratinib Pill	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Tipifarnib in Treating Patients With Advanced Hematologic Cancer	NCT00005967	Chronic Myelopr... Leukemia Lymphoma Multiple Myelom... Myelodysplastic...	tipifarnib	18 Years -	National Cancer Institute (NCI)
Donor Umbilical Cord Blood Transplant By Injection Into the Bone Marrow in Treating Patients With Hematologic Cancer	NCT00295880	Myeloproliferat... Leukemia Lymphoma Myelodysplastic...	umbilical cord ...	12 Years - 45 Years	Masonic Cancer Center, University of Minnesota
Donor Stem Cell Transplant, Pentostatin, and Total-Body Irradiation in Treating Patients With Hematological Cancer	NCT00816413	Chronic Myelopr... Leukemia Lymphoma Myelodysplastic... Nonmalignant Ne...	cyclosporine mycophenolate m... pentostatin cytogenetic ana... fluorescence in... protein analysi... flow cytometry immunoenzyme te... laboratory biom... reduced-intensi... nonmyeloablativ... peripheral bloo... total-body irra...	19 Years - 75 Years	University of Nebraska
Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia	NCT02092324	Atypical Chroni... Chronic Neutrop...	Laboratory Biom... Quality-of-Life... Questionnaire A... Ruxolitinib Pho...	18 Years -	OHSU Knight Cancer Institute

Spots Global Cancer Trial Database for chronic neutrophilic leukemia