Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation
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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: Dose Level I Drug: Dose Level 2 |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation |
- 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 ]
- 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 ]
| Enrollment: | 10 |
| Study Start Date: | May 2007 |
| Study Completion Date: | January 2010 |
| Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Phase 1: 1-3 patients will be treated in order to establish Cyclophosphamide and Clofarabine dose and to confirm reasonable safety and engraftment efficacy.
|
Drug: Dose Level I
Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic should be given prior to each dose of Clofarabine. An additional similar dose should be given prior to Cyclophosphamide dose. Clofarabine 30 mg/M2 -8 through - 4 (5 doses) infusion. Alemtuzumab on day -8 only and after Clofarabine. Cyclophosphamide 500 mg/m2 Days -8 and -7 (2 doses) given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion.
Other Name: CLOLAR
|
|
Experimental: 2
Phase II patients 4-9 will treat at the selected dose level of Clofarabine and Cyclophosphamide.
|
Drug: Dose Level 2
Hydrocortisone 100 mg IV 30 minutes prior to each dose of Clofarabine. Ondansetron 16 mg PO or IV or another comparable antiemetic should be given prior to each dose of Clofarabine. An additional similar dose should be given prior to Cyclophosphamide dose. Clofarabine 30 mg/M2 -8 through - 4 (5 doses) infusion. Alemtuzumab on day -8 only and after Clofarabine. Cyclophosphamide 1000 mg/m2 Days -8 and -7 (2 doses) given over 1 hour beginning 4 hours after the beginning of Clofarabine infusion (patients 4-9)
Other Names:
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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 |
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| United States, Pennsylvania | |
| Penn State College of Medicine, Penn State Milton S. Hershey Medical Center | |
| Hershey, Pennsylvania, United States, 17033 | |
| Principal Investigator: | David F Claxton, MD | Penn State College of Medicine |
More Information
No publications provided
| Responsible Party: | David F. Claxton, MD, Professor of Medicine, Milton S. Hershey Medical Center |
| ClinicalTrials.gov Identifier: | NCT00626626 History of Changes |
| Other Study ID Numbers: | 25223, PSU25223 |
| Study First Received: | February 20, 2008 |
| Last Updated: | January 8, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Milton S. Hershey Medical Center:
|
leukemia myelodysplastic syndrome chronic myelogenous leukemia lymphoma mantle cell lymphoma |
Additional relevant MeSH terms:
|
Hodgkin Disease Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphoma Multiple Myeloma Neoplasms, Plasma Cell Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hemorrhagic Disorders Precancerous Conditions Cyclophosphamide Clofarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 18, 2013