Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation - Full Text View

Sponsored by:	Penn State University
Information provided by:	Penn State University
ClinicalTrials.gov Identifier:	NCT00626626

Purpose

Allogeneic hematopoietic transplant is curative for many patients with hematological neoplasms but conditions to provide optimal engraftment and anti-tumor efficacy with minimal toxicity are still under way. Clofarabine is a newly licensed agent with dramatic anti-leukemic activity. Its incorporation into a regimen for pre-transplant conditioning of acute leukemia and lymphoma patients is logical, exploiting both the anti-tumor activities it is recognized to have and the immunosuppressive activity seen with drugs in its class.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndrome Chronic Myelogenous Leukemia Lymphoma Hodgkin's Lymphoma Multiple Myeloma	Drug: Cohort 1 Drug: Cohort 2 -	Phase I Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma

Drug Information available for: Cyclophosphamide Hydrocortisone Cortisol 21-phosphate Cortisol succinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone acetate Hydrocortisone cypionate Hydrocortisone hemisuccinate Proctofoam-HC Methylprednisolone Alemtuzumab Campath Diphenhydramine Diphenhydramine citrate Diphenhydramine hydrochloride Promethazine Promethazine hydrochloride Ondansetron Ondansetron hydrochloride Acetaminophen Clofarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation

Further study details as provided by Penn State University:

Primary Outcome Measures:

Establish the safety of Clofarabine and cyclophosphamide preceding allogeneic hematopoietic engraftment. Assess the efficacy of Clofarabine and cyclophosphamide as conditioning for promoting allogeneic hematopoietic engraftment. [ Time Frame: two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Observe disease free and overall survivals in acute leukemia and lymphoma patients receiving allogeneic hematopoietic transplant after Clofarabine and cyclophosphamide conditioning. [ Time Frame: Two years ] [ Designated as safety issue: No ]

Estimated Enrollment:	26
Study Start Date:	May 2007
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Cohort 1- Cyclophosphamide given to patients 1-3	Drug: Cohort 1 Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic to be given prior to each dose of clofarabine. An additional similar dose should be given prior to cyclophosphamide dose. Clofarabine 30 mg/M2 Days -8 through -4 (5 doses) infusion over 1 hour. Alemtuzumab on day -8 only after Clofarabine, patients will be premedicated with Benadryl 25mg IV, Tylenol 650 mg PO and Methylprednisolone 1 mg/kg IV. Alemtuzumab 20 mg will be administered as a single dose over 2 hours after premedication. Cyclophosphamide given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion. Cyclophosphamide 500 mg/M2 Days -8 and -7 (2 doses) this dose given to patients 1-3.
2: Experimental Cohort 2 - Cyclophosphamide given to patients 4-9 if level 1 tolerated.	Drug: Cohort 2 - Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic to be given prior to each dose of clofarabine. An additional similar dose should be given prior to cyclophosphamide dose. Clofarabine 30 mg/M2 Days -8 through -4 (5 doses) infusion over 1 hour. Alemtuzumab on day -8 only after Clofarabine, patients will be premedicated with Benadryl 25mg IV, Tylenol 650 mg PO and Methylprednisolone 1 mg/kg IV. Alemtuzumab 20 mg will be administered as a single dose over 2 hours after premedication. Cyclophosphamide given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion. Cyclophosphamide 1000 mg/M2 Days -8 and -7 (2 doses) this dose given to patients 4-9 if Level 1 tolerated.

Arms

Assigned Interventions

1: Experimental

Cohort 1- Cyclophosphamide given to patients 1-3

Drug: Cohort 1

Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic to be given prior to each dose of clofarabine. An additional similar dose should be given prior to cyclophosphamide dose. Clofarabine 30 mg/M2 Days -8 through -4 (5 doses) infusion over 1 hour. Alemtuzumab on day -8 only after Clofarabine, patients will be premedicated with Benadryl 25mg IV, Tylenol 650 mg PO and Methylprednisolone 1 mg/kg IV. Alemtuzumab 20 mg will be administered as a single dose over 2 hours after premedication. Cyclophosphamide given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion. Cyclophosphamide 500 mg/M2 Days -8 and -7 (2 doses) this dose given to patients 1-3.

2: Experimental

Cohort 2 - Cyclophosphamide given to patients 4-9 if level 1 tolerated.

Drug: Cohort 2 -

Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic to be given prior to each dose of clofarabine. An additional similar dose should be given prior to cyclophosphamide dose. Clofarabine 30 mg/M2 Days -8 through -4 (5 doses) infusion over 1 hour. Alemtuzumab on day -8 only after Clofarabine, patients will be premedicated with Benadryl 25mg IV, Tylenol 650 mg PO and Methylprednisolone 1 mg/kg IV. Alemtuzumab 20 mg will be administered as a single dose over 2 hours after premedication. Cyclophosphamide given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion. Cyclophosphamide 1000 mg/M2 Days -8 and -7 (2 doses) this dose given to patients 4-9 if Level 1 tolerated.

Detailed Description:

Non-myeloablative conditioning allows curative allogeneic hematopoietic transplantation for patients unable to tolerate more toxic conventional conditioning regiments. These regiments continue to be refined and evolve. No standard regimen is yet agreed upon. The incorporation of the newly licenses agent Clofarabine into a non-myeloablative regimen is logical given its recognized anti-leukemic activity. This study will assess the safety and efficacy of Cyclophosphamide and Clofarabine in promoting hematopoietic engraftment after allogeneic transplant of blood stem cells. Patients eligibility will include those with advanced hematological neoplasms who might benefit from allogeneic blood cell transplant. Patients must have adequate organ function and suitable related or unrelated donors for transplant. In Phase I of the study 9-12 patients will be treated in order to establish Cyclophosphamide and Clofarabine dose, and to confirm reasonable safety and engraftment efficacy. Phase II will treat at total of 20 patients at the selected dose level of Clofarabine and Cyclophosphamide. Results will be compared to extensive Penn State Milton S. Hershey Medical Center experience using Fludarabine and Cyclophosphamide in a similar patient population. Supportive care, including graft versus host disease prophylaxis will be similar to that recently used at Hershey Medical Center. Primary endpoints will include survival and engraftment as compared to historical results at Hershey Medical Center. Disease specific outcomes for frequent diagnoses such as acute leukemia and non-hodgkin's lymphoma will be assessed as secondary endpoints.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Phase I

Acute leukemia - secondary or beyond first remission or in CR with poor risk cytogenetics, myelodysplastic syndrome IPPS Int-2 or high risk, chronic myelogenous leukemia in accelerated or blast crisis and imatinib refractory or lymphoma having failed second line therapy or relapsed mantle cell lymphoma.

Phase II

Acute leukemia secondary or at high risk for relapse, myelodysplastic syndrome IPPS Int-2 or high risk or having failed other therapy, chronic myelogenous leukemia, lymphoma having failed first line therapy or at high risk, relapsed Hodgkin's, CCL progressed beyond initial therapy, multiple myeloma beyond initial response or with high risk features.
Must have an HLA matched or 5/6 matched related donor at at least a 5/6 matched unrelated donor available.
Have adequate renal and hepatic functions
Capable of understanding the investigational nature, potential risk and benefits of the study and able to provide valid informed consent.
Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
Male and female patients of childbearing potential must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

Current concomitant chemotherapy, radiation therapy or immunotherapy other than as specified in the protocol.
Use of investigational agents within 30 days and no cytotoxic anticancer agents within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all non-hematological acute toxicities from any previous therapy.
Other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment.
Patients with systemic fungal, bacterial, viral, or other infection not controlled.
Pregnant or lactating patients.
Any significant concurrent disease, illness or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up or interpretation of study results.
Age > 70 (for Phase 1) or 75 (for Phase 2)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00626626

Contacts

Contact: Tara Nisbet, RN, OCN

717-531-0003 ext 285453

tnisbet@hmc.psu.edu

Locations

United States, Pennsylvania
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center	Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Tara Nisbet, RN, OCN 717-531-0003 ext 285453 tnisbet@hmc.psu.edu

Sponsors and Collaborators

Penn State University

Investigators

Principal Investigator:

David F Claxton, MD

Penn State College of Medicine

More Information

Responsible Party:	Penn State College of Medicine ( David F. Claxton, MD )
Study ID Numbers:	25223, PSU25223
Study First Received:	February 20, 2008
Last Updated:	December 30, 2008
ClinicalTrials.gov Identifier:	NCT00626626
Health Authority:	United States: Institutional Review Board

Keywords provided by Penn State University:

leukemia
myelodysplastic syndrome
chronic myelogenous leukemia
lymphoma
mantle cell lymphoma

Study placed in the following topic categories:

Hydrocortisone
Hodgkin's disease
Precancerous Conditions
Chronic myelogenous leukemia
Methylprednisolone
Blood Protein Disorders
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Leukemia
Preleukemia
Promethazine
Hemorrhagic Disorders

Multiple myeloma
Alemtuzumab
Ondansetron
Hodgkin Disease
Lymphoma
Acetaminophen
Clofarabine
Myelodysplastic syndromes
Immunoproliferative Disorders
Cortisol succinate
Hematologic Diseases
Blood Coagulation Disorders
Myelodysplasia
Myelodysplastic Syndromes
Myeloproliferative Disorders

Additional relevant MeSH terms:

Neoplasms
Pathologic Processes
Disease
Neoplasms by Histologic Type
Immune System Diseases

Antineoplastic Agents
Therapeutic Uses
Syndrome
Cardiovascular Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009