Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation

Condition(s) targeted: Leukemia; Myelodysplastic Syndrome; Chronic Myelogenous Leukemia; Lymphoma; Hodgkin's Lymphoma; Multiple Myeloma

Intervention: Dose Level I (Drug); Dose Level 2 (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Penn State University

Official(s) and/or principal investigator(s):
David F Claxton, MD, Principal Investigator, Affiliation: Penn State College of Medicine

Overall contact:
Tara Nisbet, RN, OCN, Phone: 717-531-0003, Ext: 285453, Email: tnisbet@hmc.psu.edu

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.

Official title: Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation

Study design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: 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.

Secondary outcome: Observe disease free and overall survivals in acute leukemia and lymphoma patients receiving allogeneic hematopoietic transplant after Clofarabine and cyclophosphamide conditioning.

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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)

Tara Nisbet, RN, OCN, Phone: 717-531-0003, Ext: 285453, Email: tnisbet@hmc.psu.edu

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

Starting date: May 2007
Ending date: January 2010
Last updated: February 3, 2009