Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Syndrome

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Prolymphocytic

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Richter Syndrome

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Gemcitabine

Tacrolimus

Methotrexate

Lenograstim

Thymoglobulin

Busulfan

Clofarabine

Antilymphocyte Serum

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Adjuvants, Immunologic

Calcineurin Inhibitors

Alkylating Agents

Antineoplastic Agents, Alkylating

Folinic Acid

Folate

Vitamin B9

Participants receive gemcitabine IV over 10-25 minutes on days -6 and -4, clofarabine IV over 1 hour and busulfan IV over 3 hours on days -6 to -3. Participants with matched unrelated donors also receive anti-thymocyte globulin IV over 4 hours on days -3 to -1. Starting day -2, participants receive tacrolimus PO daily for up to 6 months. Participants undergo hematopoietic allogeneic stem cell transplant on day 0, then receive methotrexate IV over 15 minutes on days 1, 3, 6 and 11, and filgrastim SC QD beginning 1 week after transplant until blood cell levels return to normal.

Allogeneic Hematopoietic Stem Cell Transplantation

Anti-Thymocyte Globulin

Filgrastim

Chitra Hosing

This phase I/II trial studies the best dose and side effects of gemcitabine and how well it works with clofarabine and busulfan and donor stem cell transplant in treating participants with chronic lymphocytic leukemia. Drugs used in chemotherapy, such as gemcitabine, clofarabine, and busulfan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of gemcitabine when administered with busulfan and clofarabine.

II. To estimate the day 100 treatment-related mortality (TRM) for the preparative regimen busulfan, clofarabine, and gemcitabine followed by allogeneic hematopoietic cell transplantation (HCT) for patients with chronic lymphocytic leukemia (CLL).

SECONDARY OBJECTIVES:

I. To determine the rate of progression-free survival (PFS), graft versus host disease (GVHD), engraftment, and overall survival (OS) for this treatment regimen at one year post treatment completion.

OUTLINE: This is a dose-escalation study of gemcitabine.

Participants receive gemcitabine intravenously (IV) over 10-25 minutes on days -6 and -4, clofarabine IV over 1 hour and busulfan IV over 3 hours on days -6 to -3. Participants with matched unrelated donors also receive anti-thymocyte globulin IV over 4 hours on days -3 to -1. Starting day -2, participants receive tacrolimus orally (PO) daily for up to 6 months. Participants undergo hematopoietic allogeneic stem cell transplant on day 0, then receive methotrexate IV over 15 minutes on days 1, 3, 6 and 11, and filgrastim subcutaneously (SC) once daily (QD) beginning 1 week after transplant until blood cell levels return to normal.

After completion of study treatment, participants are followed up at 3, 6 and 12 months, then every 6 months for 1 year.

Allogeneic Stem Cell Transplant for CLL

Clofarabine, Gemcitabine, and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)

Number of patients without any relapse post treatment completion

The number of days until participants by dose level reach engraftment.

GvHD (Graft versus Host Disease) occurs when immune cells transplanted from a non-identical donor (graft) recognizes the transplant recipient (the host) as foreign, thereby initiating an immune reaction in the transplant recipient. Acute GvHD typically occurs around the time of engraftment and manifests in skin, GI system, and liver abnormalities. Chronic GvHD is defined by manifestations such as ocular, oral, lung, sclerosis skin, failure to thrive, fascia, cholestasis in liver, esophagus strictures.

Number of deaths related to treatment by day 100 post allogeneic transplant

To find the maximum tolerated dose (MTD) of Gemcitabine when administered with Busulfan \& Clofarabine

Will be estimated by the method of Kaplan and Meier. Time-to-event distributions as function of patient baseline covariates will be evaluated using Bayesian time-to-event regression modeling.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

At Gemcitabine Dose Level 2, there were no participants at that dose level and so the number of participants at risk for adverse events is zero.

Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant

Gemcitabine Dose Level 1

Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant

Gemcitabine Dose Level 2

Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant

Gemcitabine Dose Level 3

Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant

Gemcitabine Dose Level 4

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Diseases : Chronic Lymphocytic Leukemia (CLL)

Diseases : Prolymphocytic Leukemia (PLL)

Diseases: Richter's

Disease Category

Patients age 18-70 with CLL, PLL, or Richter's Transformation who were eligible for allogeneic transplantation

Early termination leading to small number of subjects analyzed. This study never moved to Phase II, therefore was not analyzed.

Dr. Chitra Hosing

Infection

Graft versus Host Disease (GVHD)

No participants were treated at dose level 2.

100 Day Treatment Related Mortality (TRM)

MTD analysis was for Phase II. Data were not collected.

Maximum Tolerated Dose (MTD)

All participants were registered on Phase I.

Overall Survival

Analysis was for Phase II. No analysis was done due to low accrual on Phase I.

Progression-free Survival (PFS)

Day 10

Day 11

Day 12

Day 13

Day 15

Day 17

<10 days - Graft Failure

Time-to-engraftment

Chronic GvHD (cGvHD)

Acute GvHD(aGvHD)

Acute and Chronic Graft Verse Host Disease (GvHD)

Overall Study

Recurrence

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Lymphoma

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Lymphosarcoma

Fludarabine

Fludarabine phosphate

Vorinostat

Histone Deacetylase Inhibitors

CONDITIONING REGIMEN: Patients receive vorinostat PO QD, fludarabine phosphate IV over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -6 to -3. Patients receiving a transplant from a HLA-matched unrelated donor, receive anti-thymocyte globulin IV over 4 hours on days -3 to -1.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Allogeneic Bone Marrow Transplantation

Fludarabine Phosphate

Peripheral Blood Stem Cell Transplantation

Pharmacological Study

Partow Kebriaei

This phase I trial studies the side effects and best dose of vorinostat when given together with fludarabine phosphate, clofarabine, and busulfan in treating patients with acute leukemia that is under control (remission) or has returned (relapse) undergoing donor stem cell transplant. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate, clofarabine, and busulfan, 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. Giving vorinostat together with fludarabine phosphate, clofarabine, and busulfan before a donor stem cell transplant may be a better treatment for patients with acute leukemia.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of SAHA (vorinostat) in combination with the preparative regimen fludarabine (fludarabine phosphate), clofarabine, and busulfan followed by allogeneic hematopoietic stem cell transplantation (SCT) for patients with advanced acute leukemia.

SECONDARY OBJECTIVES:

I. To determine the rate of graft versus host disease (GVHD), engraftment, progression-free survival (PFS) and overall survival (OS) for this treatment regimen.

OUTLINE: This is a dose-escalation study of vorinostat.

CONDITIONING REGIMEN: Patients receive vorinostat orally (PO) once daily (QD), fludarabine phosphate intravenously (IV) over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -6 to -3. Patients receiving a transplant from a human leukocyte antigen (HLA)-matched unrelated donor, receive anti-thymocyte globulin IV over 4 hours on days -3 to -1.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

Fludarabine Phosphate, Clofarabine, and Busulfan With Vorinostat in Treating Patients With Acute Leukemia in Remission or Relapse Undergoing Donor Stem Cell Transplant

Fludarabine/Clofarabine/Busulfan Combined With SAHA in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukemia

The 2-stage time-to-event continual reassessment method will be used. Toxicity will be tabulated by dose, type, and grade. The probability of toxicity over 30 days as a function of dose will be estimated by fitting a Bayesian binary outcome regression model.

Will be estimated by the Kaplan and Meier method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Allogeneic Stem Cell Transplant for CLL	NCT01629511	Allogeneic Hema... Chronic Lymphoc... Prolymphocytic ... Richter Syndrom...	Allogeneic Hema... Anti-Thymocyte ... Busulfan Clofarabine Filgrastim Gemcitabine Methotrexate Tacrolimus	18 Years - 70 Years	M.D. Anderson Cancer Center
Allogeneic Stem Cell Transplant for CLL	NCT01629511	Allogeneic Hema... Chronic Lymphoc... Prolymphocytic ... Richter Syndrom...	Allogeneic Hema... Anti-Thymocyte ... Busulfan Clofarabine Filgrastim Gemcitabine Methotrexate Tacrolimus	18 Years - 70 Years	M.D. Anderson Cancer Center
Fludarabine Phosphate, Clofarabine, and Busulfan With Vorinostat in Treating Patients With Acute Leukemia in Remission or Relapse Undergoing Donor Stem Cell Transplant	NCT02083250	Acute Lymphobla... Acute Myeloid L... Allogeneic Hema... Myelodysplastic... Previously Trea... Recurrent Acute... Recurrent Acute...	Allogeneic Bone... Allogeneic Hema... Anti-Thymocyte ... Busulfan Clofarabine Fludarabine Pho... Peripheral Bloo... Pharmacological... Vorinostat	- 60 Years	M.D. Anderson Cancer Center
Fludarabine Phosphate, Clofarabine, and Busulfan With Vorinostat in Treating Patients With Acute Leukemia in Remission or Relapse Undergoing Donor Stem Cell Transplant	NCT02083250	Acute Lymphobla... Acute Myeloid L... Allogeneic Hema... Myelodysplastic... Previously Trea... Recurrent Acute... Recurrent Acute...	Allogeneic Bone... Allogeneic Hema... Anti-Thymocyte ... Busulfan Clofarabine Fludarabine Pho... Peripheral Bloo... Pharmacological... Vorinostat	- 60 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for allogeneic hematopoietic stem cell transplantation recipient