Hodgkin LymphomaPhase 1NCT01900509
Bendamustine Hydrochloride, Clofarabine, and Etoposide in Treating Younger Patients With Relapsed or Refractory Hematologic Malignancies
A Phase 1 study testing Bendamustine, Clofarabine and Etoposide in people with Hodgkin Lymphoma and Non-Hodgkin Lymphoma, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Participants with relapsed or refractory leukemia or lymphoma will be recruited for this study to find whether or not the addition of a new drug called bendamustine will be safe and possible to give with other chemotherapy drugs. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Acute Leukemia
- What is being tested?
- Bendamustine, Clofarabine and Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants with Hodgkin or Non-Hodgkin lymphoma must meet one of the following criteria: (a) Relapsing disease in 2nd or greater relapse and measurable disease, or (b) Refractory disease failing to achieve complete remission (CR) with > 2 induction or re-induction attempts.
- Participant with acute leukemia must meet one of the following criteria: (a) Relapsing acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or acute biphenotypic leukemia in 2nd or greater relapse; or (b) Refractory ALL, AML, or acute biphenotypic leukemia failing to achieve CR with ≥ 2 induction or re-induction attempts.
- Participant with leukemia has M2 or M3 marrow at the time of enrollment. Participant with M2 marrow must have definite cytogenetic, molecular, or immunophenotypic evidence of recurrent/refractory disease.
- Age is ≤ 21 years (participant has not yet reached 22nd birthday).
- Karnofsky or Lansky performance score is ≥ 60%. The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ≥ 16 years.
- There are no known contra-indications to any of the planned agents used in this protocol. Etoposide may be substituted by etoposide phosphate (etopophos) if the patient has a history of hypersensitivity reaction to etoposide
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- Adequate renal function defined as glomerular filtration rate > 60 cc/min/1.73m2, or normal serum creatinine based on age.
- Adequate hepatic function: (a) Direct bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, direct bilirubin is ≤ 1.4 mg/dl, and (b) AST and ALT ≤ 5 x ULN for age.
- Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection fraction ≥ 45%.
- Lymphoma participants without bone marrow involvement must have: (a) Absolute neutrophil count (ANC) ≥ 1,000/µL, and (b) Platelet count > 50,000/mm^3 (without transfusion support). [Note: these criteria are waived for participants with leukemia or lymphoma participants with bone marrow involvement.]
- Participant must have recovered from the acute side effects of all prior anti-cancer therapy, and :
- At least 2 weeks have elapsed since prior systemic cytotoxic chemotherapy (except intrathecal chemotherapy, and/or low dose maintenance therapy such as vincristine, mercaptopurine, methotrexate or glucocorticoids), and
- At least 4 weeks have elapsed since treatment with an investigational agent or antibody-based therapy, if applicable, and
- If the participant received a prior allogeneic hematopoietic stem cell transplantation (HSCT), at least 3 months have elapsed and there is no evidence of active graft-versus-host disease (GVHD), participant has discontinued immunosuppression, and there is no history of veno-occlusive disease.
Who cannot join
- Active, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illness.
- Isolated extramedullary disease (leukemia).
- Primary CNS lymphoma.
- Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment).
- Known HIV or active hepatitis B or C infection.
- Known hypersensitivity to bendamustine or mannitol.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: A Phase I Trial of Bendamustine in Combination With Clofarabine and Etoposide in Pediatric Patients With Relapsed or Refractory Hematologic Malignancies
Participants with relapsed or refractory leukemia or lymphoma will be recruited for this study to find whether or not the addition of a new drug called bendamustine will be safe and possible to give with other chemotherapy drugs. This drug is approved by the Food and Drug Administration (FDA) for the treatment of other cancers in adults that are similar to those being studied in the research trial.
PRIMARY OBJECTIVES
Read more
- To establish the maximum tolerated dose (MTD) of bendamustine in combination with clofarabine and etoposide in pediatric participants with hematologic malignancies.
- To characterize the safety profile and dose-limiting toxicities (DLTs) of bendamustine in combination with clofarabine and etoposide.
SECONDARY OBJECTIVES
- To estimate event-free survival at 4 months.
- To estimate minimal residual disease (MRD) levels present at end of each cycle of therapy in participants with leukemia.
- To characterize the pharmacokinetic profile of bendamustine in the proposed regimen.
Read the detailed description
Bendamustine will be combined with clofarabine and etoposide in a five-day cycle. Dexamethasone will be given to prevent capillary leak syndrome associated with clofarabine.
If the participant does not develop progressive disease or a dose-limiting toxicity (DLT) during the first cycle, a second cycle may be administered as a bridge to transplant. Each cycle lasts 21-28 days (or until count recovery).
Concomitant intrathecal therapy can be given at the investigator's discretion, but not on the same days as chemotherapy. Recommendations are triple intrathecal therapy (methotrexate, hydrocortisone, cytarabine) weekly for participants with CNS2 or CNS3 disease, and every two weeks for participants with CNS1 disease. Leucovorin may be given according to institutional guidelines.
The intent of this study design is for all participants to receive and complete one course of therapy. Participants who exhibit signs of disease progression or experience an unacceptable toxicity will be discontinued from protocol treatment.
- Conditions
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Acute Leukemia
- Being tested
- Bendamustine, Clofarabine, Etoposide, Etoposide phosphate, Dexamethasone
- Keywords
- Childhood leukemia, Childhood lymphoma, Bendamustine
- Medical subject headings
- Hodgkin Disease, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Also called Treanda(R), Bendamustine hydrochloride
Route of administration: intravenously (IV) over approximately 60 minutes, days 1-5.
ClofarabineDrug
Also called Clolar(TM), Clofarex
Route of administration: IV days 1-5.
EtoposideDrug
Also called VP-16, Vepesid(R)
Route of administration: IV days 1-5.
Etoposide phosphateDrug
Also called Etopophos(R)
Route of administration: Used in substitution for etoposide in participants who experience allergic reaction, Etopophos® will be administered IV.
DexamethasoneDrug
Also called Decadron(R)
Route of administration: three times daily orally (by mouth), days 1-5.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | All participants who meet eligibility for this study will follow the same treatment regimen.
INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone. Receives: Drug: Bendamustine; Drug: Clofarabine; Drug: Etoposide; Drug: Etoposide phosphate; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Establish MTD of bendamustine in combination with clofarabine and etoposide.
Measured: Continually throughout the study (up to 3 months)
Dose limiting toxicities
Characterize safety profile and DLTs of bendamustine in combination with clofarabine and etoposide
Measured: Continually throughout the study (up to 3 months)
Secondary outcomes (3)
Event free survival
Event-free survival (EFS) time will be calculated from on therapy to any kind of failure or to last contact date for participants who are alive without any failure at the last contact date. The time to EFS will be set to 0 for participants who fail to achieve complete remission. Kaplan-Meier estimates of EFS curves will be computed, along with estimates of standard errors by the method of Peto. Four month EFS, as well as longer term survival rates (6 month and 1 year) will be estimated with 95% confidence intervals.
Measured: 4 months after the start of therapy for the last patient enrolled on the study
Proportion of leukemia participants with positive minimal residual disease
The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Measured: At end of each cycle of chemotherapy (approximately at 1 month and 2 months)
Plasma concentration of bendamustine
Plasma concentrations of bendamustine will be measured using an established LC-MS/MS assay. Bendamustine pharmacokinetic parameters such as Cmax, tmax, AUC (0-t), t1/2, and clearance will be estimated using population-based modeling techniques.
Measured: Day 1 and day 5 of cycle 1 therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2013 (estimated)
- Study startAug 2013
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Teva Pharmaceuticals USA
- Responsible party
- Sponsor
- Investigators
- Sima Jeha, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01900509
- Sponsor's protocol ID
- BECHEM
- Other IDs
- TEVA ISS, NCI-2013-01148
- Status last verified
- Mar 2017
- First submitted
- 11 Jul 2013
- Last updated
- 22 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Jeha S, Crews KR, Pei D, Peyton M, Panetta JC, Ribeiro RC, Zhao X, Campbell P, Metzger ML, Yang JJ, Cheng C, Pui CH, Bhojwani D. Phase 1 study of bendamustine in combination with clofarabine, etoposide, and dexamethasone in pediatric patients with relapsed or refractory hematologic malignancies. Cancer. 2021 Jun 15;127(12):2074-2082. doi: 10.1002/cncr.33465. Epub 2021 Feb 17.
PubMed 33598942
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Bendamustine in Combination With Clofarabine and Etoposide in Pediatric Patients With Relapsed or Refractory Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01900509
- Acronym / sponsor ID
- BECHEM
- Conditions
- Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Acute Leukemia
- Keywords
- Childhood leukemia, Childhood lymphoma, Bendamustine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- Teva Pharmaceuticals USA
- Study start
- Aug 2013
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 16 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Participants with relapsed or refractory leukemia or lymphoma will be recruited for this study to find whether or not the addition of a new drug called bendamustine will be safe and possible to give with other chemotherapy drugs. This drug is approved by the Food and Drug Administration (FDA) for the treatment of other cancers in adults that are similar to those being studied in the research trial.
PRIMARY OBJECTIVES
- To establish the maximum tolerated dose (MTD) of bendamustine in combination with clofarabine and etoposide in pediatric participants with hematologic malignancies.
- To characterize the safety profile and dose-limiting toxicities (DLTs) of bendamustine in combination with clofarabine and etoposide.
SECONDARY OBJECTIVES
- To estimate event-free survival at 4 months.
- To estimate minimal residual disease (MRD) levels present at end of each cycle of therapy in participants with leukemia.
- To characterize the pharmacokinetic profile of bendamustine in the proposed regimen.
Detailed description
Bendamustine will be combined with clofarabine and etoposide in a five-day cycle. Dexamethasone will be given to prevent capillary leak syndrome associated with clofarabine.
If the participant does not develop progressive disease or a dose-limiting toxicity (DLT) during the first cycle, a second cycle may be administered as a bridge to transplant. Each cycle lasts 21-28 days (or until count recovery).
Concomitant intrathecal therapy can be given at the investigator's discretion, but not on the same days as chemotherapy. Recommendations are triple intrathecal therapy (methotrexate, hydrocortisone, cytarabine) weekly for participants with CNS2 or CNS3 disease, and every two weeks for participants with CNS1 disease. Leucovorin may be given according to institutional guidelines.
The intent of this study design is for all participants to receive and complete one course of therapy. Participants who exhibit signs of disease progression or experience an unacceptable toxicity will be discontinued from protocol treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Bendamustine, Drug: Clofarabine, Drug: Etoposide, Drug: Etoposide phosphate, Drug: DexamethasoneAll participants who meet eligibility for this study will follow the same treatment regimen. INTERVENTIONS: bendamustine, clofarabine, etoposide (or etoposide phosphate), dexamethasone. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Participants with Hodgkin or Non-Hodgkin lymphoma must meet one of the following criteria: (a) Relapsing disease in 2nd or greater relapse and measurable disease, or (b) Refractory disease failing to achieve complete remission (CR) with > 2 induction or re-induction attempts.
- Participant with acute leukemia must meet one of the following criteria: (a) Relapsing acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or acute biphenotypic leukemia in 2nd or greater relapse; or (b) Refractory ALL, AML, or acute biphenotypic leukemia failing to achieve CR with ≥ 2 induction or re-induction attempts.
- Participant with leukemia has M2 or M3 marrow at the time of enrollment. Participant with M2 marrow must have definite cytogenetic, molecular, or immunophenotypic evidence of recurrent/refractory disease.
- Age is ≤ 21 years (participant has not yet reached 22nd birthday).
- Karnofsky or Lansky performance score is ≥ 60%. The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ≥ 16 years.
Key exclusion criteria (6 listed)
- Active, uncontrolled infection or severe concurrent medical disease, including but not limited to congestive heart failure, cardiac arrhythmias, or psychiatric illness.
- Isolated extramedullary disease (leukemia).
- Primary CNS lymphoma.
- Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment).
- Known HIV or active hepatitis B or C infection.
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 |
|---|---|---|
| BendamustineAlso: Treanda(R), Bendamustine hydrochlorideRoute of administration: intravenously (IV) over approximately 60 minutes, days 1-5. | Drug | Treatment |
| ClofarabineAlso: Clolar(TM), ClofarexRoute of administration: IV days 1-5. | Drug | Treatment |
| EtoposideAlso: VP-16, Vepesid(R)Route of administration: IV days 1-5. | Drug | Treatment |
| Etoposide phosphateAlso: Etopophos(R)Route of administration: Used in substitution for etoposide in participants who experience allergic reaction, Etopophos® will be administered IV. | Drug | Treatment |
| DexamethasoneAlso: Decadron(R)Route of administration: three times daily orally (by mouth), days 1-5. | Drug | Treatment |
Primary outcome
Maximum tolerated dose
Time frame: Continually throughout the study (up to 3 months)
Establish MTD of bendamustine in combination with clofarabine and etoposide.
Dose limiting toxicities
Time frame: Continually throughout the study (up to 3 months)
Characterize safety profile and DLTs of bendamustine in combination with clofarabine and etoposide
3 secondary outcomes
Event free survival
Time frame: 4 months after the start of therapy for the last patient enrolled on the study
Proportion of leukemia participants with positive minimal residual disease
Time frame: At end of each cycle of chemotherapy (approximately at 1 month and 2 months)
Plasma concentration of bendamustine
Time frame: Day 1 and day 5 of cycle 1 therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2017.
- Derived from this study: PubMed 33598942Jeha S, Crews KR, Pei D, Peyton M, Panetta JC, Ribeiro RC, Zhao X, Campbell P, Metzger ML, Yang JJ, Cheng C, Pui CH, Bhojwani D. Phase 1 study of bendamustine in combination with clofarabine, etoposide, and dexamethasone in pediatric patients with relapsed or refractory hematologic malignancies. Cancer. 2021 Jun 15;127(12):2074-2082. doi: 10.1002/cncr.33465. Epub 2021 Feb 17.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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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.
Sima Jeha, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bendamustine, Clofarabine and Etoposide in people with Hodgkin Lymphoma and Non-Hodgkin Lymphoma, run by St. Jude Children's Research Hospital 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 14 inclusion and 6 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: finished, as of the sponsor's last update on 22 Mar 2017. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (time frame: Continually throughout the study (up to 3 months)). 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?
On the ClinicalTrials.gov record for NCT01900509, 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 22 Mar 2017.