Acute Lymphoblastic LeukemiaPhase 1/2NCT00983528
Alemtuzumab and Clofarabine for Relapsed or Refractory Acute Lymphoblastic Leukemia
A Phase 1/2 study testing Alemtuzumab and Clofarabine in people with Acute Lymphoblastic Leukemia, run by University of California, San Diego at 3 sites in United States.
Trial summary
Clofarabine is approved by the FDA for the treatment of pediatric patients (1 to 21 years of age) with relapsed or refractory ALL. Alemtuzumab is approved by the FDA for treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients over the age of 18. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- Alemtuzumab and Clofarabine
- How many people
- 6 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2009to Sep 2011
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Provide signed written informed consent. If a patient is under the 18 years of age the parent or the guardian will also need to provide written informed consent.
- Diagnosis of ALL (B or T lineage) who have received therapy with at least 1 but not more than 3 prior different induction regimens and have been deemed to have relapse or refractory disease. The phase II component of the study enrollment will be limited to 2 different prior induction regimens if patients are older than 30 years.
- ALL lymphoblasts with CD52 expression on at least 10% on lymphoblasts.
- Age >= 16 years of age.
- ECOG PS 0-2.
- Have adequate renal and hepatic functions.
Show all 10Show fewer
- Subject or their patient or guardian is capable of understanding the investigational nature, potential risks 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 must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. Subjects 16 and 17 years old must also adhere to effective contraception methods or abstinence during the study and for a minimum of 6 months after study and the nature of contraception or abstinence must be documented.
- CMV PCR negative prior to enrollment
Who cannot join
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea, CNS treatment or prophylaxis, or tyrosine kinase inhibitors for individuals with Philadelphia chromosome positive ALL. The patient must have recovered from all acute toxicities from any previous therapy.
- Lack of bone marrow or blood involvement by leukemia such as a documented CNS or testicular only relapse.
- Have any 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 any known or suspected Hepatitis B, C and HIV infections.
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, 92093
UCSD Medical Center
San Diego, California, 92103
Rady Children's Hospital
San Diego, California, 92123
About this study
Official title: A Phase I/II Study of Alemtuzumab and Clofarabine for Relapsed or Refractory Acute Lymphoblastic Leukemia
Clofarabine is approved by the FDA for the treatment of pediatric patients (1 to 21 years of age) with relapsed or refractory ALL. Alemtuzumab is approved by the FDA for treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients over the age of 18. These drugs have been used to treat patients with leukemia in other research studies like this one. Both drugs have individually been administered to adult patients with ALL with acceptable toxicity profiles. This study will evaluate the combination of clofarabine and alemtuzumab when administered to adult patients with relapsed or refractory ALL. Primary objectives of the study is to determine the maximum tolerated dose of clofarabine when administered with alemtuzumab, evaluate the safety of the combination, and assess for activity of the combination by evaluating response rate, effect on ALL progenitor cell population, and patients who are able to bridge to transplant.
Read the detailed description
The strategy for treating relapsed and refractory adult ALL patients is through reinduction chemotherapy followed by allogeneic stem cell transplantation, provided that the toxicity of the salvage regimen is acceptable. However, this leukemia is characterized as being highly refractory to standard chemotherapy and therefore novel therapeutic approaches are desperately needed. Clofarabine is a second generation nucleoside analog FDA approved for the treatment of relapsed and refractory pediatric ALL. Clofarabine has been administered to adult patients with hematologic malignancies with an acceptable toxicity profile with 8% of relapsed ALL patients attaining a complete response (CR). The maximum tolerated dose (MTD) of clofarabine IV in adult patients has been determined to be 40 mg/m2/day for 5 consecutive days, which is lower than the tolerable daily dose for pediatric patients, 52 mg/m2/day. More recently, Karp and colleagues reported their experience with clofarabine in combination with cyclophosphamide in 18 patients with refractory acute leukemias. Encouraging responses were seen in the refractory ALL patients with 67% (4/6) patients experiencing a CR. Toxicity did not allow dose escalation of clofarabine and the MTD was defined as 10 mg/m2 administered over 6 non-consecutive days when combined with cyclophosphamide 200-400mg/m2 over a total of 7 days per cycle. As such, we are conservatively evaluating a clofarabine dose of 20mg/m2 for five days with a dose de-escalation step if there is dose limiting toxicity.
The addition of monoclonal antibody therapy is an attractive approach in the treatment of relapsed and refractory ALL since it targets both B and T progenitor ALL subtypes and has different mechanisms of action and side effects than chemotherapy. Alemtuzumab is a humanized monoclonal antibody to CD52 which is expressed on the majority of neoplastic lymphocytes, including 70% of ALL and 100% of Philadelphia positive ALL. The CALGB evaluated alemtuzumab as consolidation in front-line therapy for patients with ALL and demonstrated feasibility and found alemtuzumab administration at 30mg subcutaneously administered for 12 doses to be safe and well tolerated in a frontline consolidation setting in ALL. In the present protocol targeting refractory and relapsed ALL patients, the maximal alemtuzumab dose will be 30 mg as in Stock's study, but will be administered intravenously in order to improve the induction chemotherapy pharmacokinetics. Premedication with dexamethasone, benadryl, and acetaminophen will be given to all patients prior to alemtuzumab infusion to prevent infusional reactions associated with intravenous dosing.
The combination of purine analogs and alemtuzumab have been administered simultaneously safely with promising additive activity in other relapsed and refractory lymphocytic leukemias. A recent case series reported patients with relapsed and/or refractory ALL who failed several induction chemotherapies to achieve complete responses to fludarabine and alemtuzumab combination regimens. All patients were able to proceed to allogeneic SCT with refractory ALL patient relapsing at 8 months while relapsed patients remain in remission at 6 and 24 months.
Other approaches utilizing combination chemotherapy have failed to demonstrate consistent activity that would qualify them as standard of care. Therefore the standard of care for patients with relapsed and refractory ALL is enrollment into clinical trials.
All patients will receive alemtuzumab in a dose escalation fashion (3, 10, 30mg). Successive escalating doses will be administered if the previous dose is tolerated. Previously, Stock et al established the safety of 12 doses of 30mg of alemtuzumab in ALL. The treatment regimen is designed to have alemtuzumab administered prior to administration of clofarabine to allow dose escalation of the monoclonal antibody and decrease confounding acute toxicities such as infusion reactions and cytokine release. Clofarabine dose is modeled after previous trials in adult and pediatric ALL. The starting dose of clofarabine is lower than standard phase II doses for adult hematologic malignancy to conservatively evaluate tolerability and toxicity of clofarabine in combination with alemtuzumab. Alemtuzumab dosing will be limited to a total of 12. However, patients can continue with additional cycles of clofarabine if they do not show progressive disease or have unacceptable toxicity.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- Alemtuzumab, Clofarabine
- Keywords
- cancer, lymphoblastic, leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlemtuzumabBiological
Also called Campath
3mg day 1,10mg day 2, 30mg day 3, 30mg day 5, 30mg day 8, then three times per calendar week thereafter for a total 12- 30mg doses
ClofarabineDrug
Also called Clolar
Dose Escalation
Cycle 1 (30 days or until alemtuzumab completed) Clofarabine 10,20,30 or 40 mg/m2 days 5-9
Cycle 2 and subsequent cycles (administered no more frequently than every 28 days) 10,20,30 or 40 mg/m2 days 1-5
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine the Maximum Tolerated Dose of Clofarabine When Administered in Combination With Alemtuzumab as Measured by CTC Version 3.0. (Phase 1)
Measured: 2 years
Number of Adverse Events
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 posted24 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionSep 2011
- Study completionSep 2011
Why it stopped: Support withdrawn due to slow accrual
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.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00983528
- Sponsor's protocol ID
- 090331
- Status last verified
- Jul 2020
- First submitted
- 23 Sep 2009
- Last updated
- 12 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Alemtuzumab and Clofarabine for Relapsed or Refractory Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT00983528
- Acronym / sponsor ID
- 090331
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- cancer, lymphoblastic, leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Support withdrawn due to slow accrual
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Sep 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 24 Sep 2009 (estimated)
- Results
- Posted 12 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clofarabine is approved by the FDA for the treatment of pediatric patients (1 to 21 years of age) with relapsed or refractory ALL. Alemtuzumab is approved by the FDA for treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients over the age of 18. These drugs have been used to treat patients with leukemia in other research studies like this one. Both drugs have individually been administered to adult patients with ALL with acceptable toxicity profiles. This study will evaluate the combination of clofarabine and alemtuzumab when administered to adult patients with relapsed or refractory ALL. Primary objectives of the study is to determine the maximum tolerated dose of clofarabine when administered with alemtuzumab, evaluate the safety of the combination, and assess for activity of the combination by evaluating response rate, effect on ALL progenitor cell population, and patients who are able to bridge to transplant.
Detailed description
The strategy for treating relapsed and refractory adult ALL patients is through reinduction chemotherapy followed by allogeneic stem cell transplantation, provided that the toxicity of the salvage regimen is acceptable. However, this leukemia is characterized as being highly refractory to standard chemotherapy and therefore novel therapeutic approaches are desperately needed. Clofarabine is a second generation nucleoside analog FDA approved for the treatment of relapsed and refractory pediatric ALL. Clofarabine has been administered to adult patients with hematologic malignancies with an acceptable toxicity profile with 8% of relapsed ALL patients attaining a complete response (CR). The maximum tolerated dose (MTD) of clofarabine IV in adult patients has been determined to be 40 mg/m2/day for 5 consecutive days, which is lower than the tolerable daily dose for pediatric patients, 52 mg/m2/day. More recently, Karp and colleagues reported their experience with clofarabine in combination with cyclophosphamide in 18 patients with refractory acute leukemias. Encouraging responses were seen in the refractory ALL patients with 67% (4/6) patients experiencing a CR. Toxicity did not allow dose escalation of clofarabine and the MTD was defined as 10 mg/m2 administered over 6 non-consecutive days when combined with cyclophosphamide 200-400mg/m2 over a total of 7 days per cycle. As such, we are conservatively evaluating a clofarabine dose of 20mg/m2 for five days with a dose de-escalation step if there is dose limiting toxicity.
The addition of monoclonal antibody therapy is an attractive approach in the treatment of relapsed and refractory ALL since it targets both B and T progenitor ALL subtypes and has different mechanisms of action and side effects than chemotherapy. Alemtuzumab is a humanized monoclonal antibody to CD52 which is expressed on the majority of neoplastic lymphocytes, including 70% of ALL and 100% of Philadelphia positive ALL. The CALGB evaluated alemtuzumab as consolidation in front-line therapy for patients with ALL and demonstrated feasibility and found alemtuzumab administration at 30mg subcutaneously administered for 12 doses to be safe and well tolerated in a frontline consolidation setting in ALL. In the present protocol targeting refractory and relapsed ALL patients, the maximal alemtuzumab dose will be 30 mg as in Stock's study, but will be administered intravenously in order to improve the induction chemotherapy pharmacokinetics. Premedication with dexamethasone, benadryl, and acetaminophen will be given to all patients prior to alemtuzumab infusion to prevent infusional reactions associated with intravenous dosing.
The combination of purine analogs and alemtuzumab have been administered simultaneously safely with promising additive activity in other relapsed and refractory lymphocytic leukemias. A recent case series reported patients with relapsed and/or refractory ALL who failed several induction chemotherapies to achieve complete responses to fludarabine and alemtuzumab combination regimens. All patients were able to proceed to allogeneic SCT with refractory ALL patient relapsing at 8 months while relapsed patients remain in remission at 6 and 24 months.
Other approaches utilizing combination chemotherapy have failed to demonstrate consistent activity that would qualify them as standard of care. Therefore the standard of care for patients with relapsed and refractory ALL is enrollment into clinical trials.
All patients will receive alemtuzumab in a dose escalation fashion (3, 10, 30mg). Successive escalating doses will be administered if the previous dose is tolerated. Previously, Stock et al established the safety of 12 doses of 30mg of alemtuzumab in ALL. The treatment regimen is designed to have alemtuzumab administered prior to administration of clofarabine to allow dose escalation of the monoclonal antibody and decrease confounding acute toxicities such as infusion reactions and cytokine release. Clofarabine dose is modeled after previous trials in adult and pediatric ALL. The starting dose of clofarabine is lower than standard phase II doses for adult hematologic malignancy to conservatively evaluate tolerability and toxicity of clofarabine in combination with alemtuzumab. Alemtuzumab dosing will be limited to a total of 12. However, patients can continue with additional cycles of clofarabine if they do not show progressive disease or have unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Provide signed written informed consent. If a patient is under the 18 years of age the parent or the guardian will also need to provide written informed consent.
- Diagnosis of ALL (B or T lineage) who have received therapy with at least 1 but not more than 3 prior different induction regimens and have been deemed to have relapse or refractory disease. The phase II component of the study enrollment will be limited to 2 different prior induction regimens if patients are older than 30 years.
- ALL lymphoblasts with CD52 expression on at least 10% on lymphoblasts.
- Age >= 16 years of age.
- ECOG PS 0-2.
Key exclusion criteria (8 listed)
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea, CNS treatment or prophylaxis, or tyrosine kinase inhibitors for individuals with Philadelphia chromosome positive ALL. The patient must have recovered from all acute toxicities from any previous therapy.
- Lack of bone marrow or blood involvement by leukemia such as a documented CNS or testicular only relapse.
- Have any 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 any known or suspected Hepatitis B, C and HIV infections.
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 |
|---|---|---|
| AlemtuzumabAlso: Campath3mg day 1,10mg day 2, 30mg day 3, 30mg day 5, 30mg day 8, then three times per calendar week thereafter for a total 12- 30mg doses | Biological | – |
| ClofarabineAlso: ClolarDose Escalation Cycle 1 (30 days or until alemtuzumab completed) Clofarabine 10,20,30 or 40 mg/m2 days 5-9 Cycle 2 and subsequent cycles (administered no more frequently than every 28 days) 10,20,30 or 40 mg/m2 days 1-5 | Drug | – |
Primary outcome
To Determine the Maximum Tolerated Dose of Clofarabine When Administered in Combination With Alemtuzumab as Measured by CTC Version 3.0. (Phase 1)
Time frame: 2 years
Number of Adverse Events
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 12 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites 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 Alemtuzumab and Clofarabine in people with Acute Lymphoblastic Leukemia, run by University of California, San Diego at 3 sites 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 10 inclusion and 8 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 12 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 12 Aug 2020). 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?
To Determine the Maximum Tolerated Dose of Clofarabine When Administered in Combination With Alemtuzumab as Measured by CTC Version 3.0. (Phase 1) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Aug 2020.