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.
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.
- 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.
- 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
- 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
- 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)