LeukemiaPhase 1/2NCT00626626
Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation
A Phase 1/2 study testing Clofar, Cyclophos, Alemtuzumab and Clofar, Cyclophos,Alemtuzumab(Ph II) in people with Leukemia and Myelodysplastic Syndrome, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndrome, Chronic Myelogenous Leukemia
- What is being tested?
- Clofar, Cyclophos, Alemtuzumab and Clofar, Cyclophos,Alemtuzumab(Ph II)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Jan 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
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.
Read the 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.
- Conditions
- Leukemia, Myelodysplastic Syndrome, Chronic Myelogenous Leukemia, Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma
- Being tested
- Clofar, Cyclophos, Alemtuzumab, Clofar, Cyclophos,Alemtuzumab(Ph II)
- Keywords
- leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, lymphoma, mantle cell lymphoma
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Hodgkin Disease, Multiple Myeloma, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clofar, Cyclophos, AlemtuzumabDrug
Also called CLOLAR
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.
Clofar, Cyclophos,Alemtuzumab(Ph II)Drug
Also called Clolar, Campath
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)
| Study group | Role | What they receive |
|---|---|---|
| "Clofar, Cyclophos, Alemtuzumab" | Experimental | 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 - Clofarabine,Cyclophosphamide \& Alemtuzumab - Clofar (30mg/m2) D -8 to -4; Cyclo (500mg/m2) D -8 \& -7 \& Alem (20mg over 2hrs) Receives: Drug: Clofar, Cyclophos, Alemtuzumab |
| "Clofar, Cyclophos,Alemtuzumab(Ph II)" | Experimental | Phase II patients 4-9 will treat at the selected dose level of Clofarabine and Cyclophosphamide.
Drug - Clofarabine, Cyclophosphamide \& Alemtuzumab Clofar (30mg/m2) D -8 to -4; Cyclo (1000mg/m2) D -8 \& -7 \& Alem (20mg)-pts. Receives: Drug: Clofar, Cyclophos,Alemtuzumab(Ph II) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment of Allogeneic Blood Cells.
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.
Adequacy of engraftment will be assessed via assessment of chimerism (percent donor engraftment). Less than 20% engraftment by day 30 is then failure of engraftment.
Safety is defined per common toxicity criteria - Non-Hematological and non renal toxicities of ≥grade 3 or ≥grade 4 up to day 30 are scored as toxicity.
Measured: two years
Secondary outcomes (2)
Disease-Free Survival
Observe disease free survivals in acute leukemia and lymphoma patients receiving allogeneic hematopoietic transplant after Clofarabine and cyclophosphamide conditioning.
Measured: Two years
Overall Survival
Observe overall survival in leukemia and lymphoma patients receiving transplant after clofarabine and cyclophosphamide conditioning.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2008 (estimated)
- Study startMay 2007
- Primary completionJan 2010
- Study completionJan 2010
Why it stopped: Investigator decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David F. Claxton, MD, Milton S. Hershey Medical Center
- Investigators
- David F Claxton, MD, Principal investigator, Penn State College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00626626
- Sponsor's protocol ID
- 25223
- Status last verified
- Mar 2018
- First submitted
- 20 Feb 2008
- Last updated
- 25 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Karch J, Zhu J, Ehmann WC, Claxton D. Clofarabine and CY do not yield reliable engraftment of hematopoietic stem cells. Bone Marrow Transplant. 2012 Aug;47(8):1134-5. doi: 10.1038/bmt.2011.224. Epub 2011 Nov 14. No abstract available.
PubMed 22080968
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clofarabine and Non-Myeloablative Allogeneic Hematopoietic Transplantation
- ClinicalTrials.gov ID
- NCT00626626
- Acronym / sponsor ID
- 25223
- Conditions
- Leukemia, Myelodysplastic Syndrome, Chronic Myelogenous Leukemia, Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma
- Keywords
- leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, lymphoma, mantle cell lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigator decision
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 29 Feb 2008 (estimated)
- Results
- Posted 25 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| "Clofar, Cyclophos, Alemtuzumab" | Experimental | Drug: Clofar, Cyclophos, AlemtuzumabPhase 1: 1-3 patients will be treated in order to establish Cyclophosphamide and Clofarabine dose and to confirm reasonable safety and engraftment efficacy. Drug - Clofarabine,Cyclophosphamide \& Alemtuzumab - Clofar (30mg/m2) D -8 to -4; Cyclo (500mg/m2) D -8 \& -7 \& Alem (20mg over 2hrs) |
| "Clofar, Cyclophos,Alemtuzumab(Ph II)" | Experimental | Drug: Clofar, Cyclophos,Alemtuzumab(Ph II)Phase II patients 4-9 will treat at the selected dose level of Clofarabine and Cyclophosphamide. Drug - Clofarabine, Cyclophosphamide \& Alemtuzumab Clofar (30mg/m2) D -8 to -4; Cyclo (1000mg/m2) D -8 \& -7 \& Alem (20mg)-pts. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clofar, Cyclophos, AlemtuzumabAlso: CLOLARHydrocortisone 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. | Drug | "Clofar, Cyclophos, Alemtuzumab" |
| Clofar, Cyclophos,Alemtuzumab(Ph II)Also: Clolar, CampathHydrocortisone 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) | Drug | "Clofar, Cyclophos,Alemtuzumab(Ph II)" |
Primary outcome
Engraftment of Allogeneic Blood Cells.
Time frame: two years
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. Adequacy of engraftment will be assessed via assessment of chimerism (percent donor engraftment). Less than 20% engraftment by day 30 is then failure of engraftment. Safety is defined per common toxicity criteria - Non-Hematological and non renal toxicities of ≥grade 3 or ≥grade 4 up to day 30 are scored as toxicity.
2 secondary outcomes
Disease-Free Survival
Time frame: Two years
Overall Survival
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22080968Karch J, Zhu J, Ehmann WC, Claxton D. Clofarabine and CY do not yield reliable engraftment of hematopoietic stem cells. Bone Marrow Transplant. 2012 Aug;47(8):1134-5. doi: 10.1038/bmt.2011.224. Epub 2011 Nov 14. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David F Claxton, MD principal investigator
Penn State College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Clofar, Cyclophos, Alemtuzumab and Clofar, Cyclophos,Alemtuzumab(Ph II) in people with Leukemia and Myelodysplastic Syndrome, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Engraftment of Allogeneic Blood Cells. (time frame: two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00626626, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2018.