Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma
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|ClinicalTrials.gov Identifier: NCT02518750|
Recruitment Status : Terminated (Due to slow accrual)
First Posted : August 10, 2015
Results First Posted : April 3, 2019
Last Update Posted : April 3, 2019
This is a phase-II study to evaluate the efficacy of a salvage regimen in children with relapsed T-cell ALL or lymphoma. Peg-asparaginase, mitoxantrone, intrathecal triples (IT) (intrathecal methotrexate/hydrocortisone/cytarabine) (ITMHA) and dexamethasone are commonly used drugs to treat relapsed or refractory acute lymphocytic leukemia or lymphoma (ALL). In this study, the investigators want to know if adding three drugs called panobinostat, bortezomib and liposomal vincristine (VSLI) to this regimen will result in remission (no signs or symptoms of leukemia or lymphoma).
- Panobinostat has been approved by the FDA for treating adults with multiple myeloma, but it has not been approved for use in children and has not been given together with the other drugs used in this study. It has not been widely studied in children.
- VSLI has been approved by the FDA for adults with relapsed or refractory ALL, but has not yet been approved for treating children with leukemia or lymphoma.
- Bortezomib has been approved by the FDA for treating adults with a cancer called multiple myeloma and adults with relapsed mantle cell lymphoma; it has not been approved for treating children.
- To estimate the complete remission (CR) rate for patients with T-cell lymphoblastic leukemia and lymphoma in first relapse.
- To evaluate minimal residual disease (MRD) levels at end of each block of therapy.
- To describe the toxicities of vincristine sulfate liposome injection (VSLI) when used in combination with chemotherapy and bortezomib.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia Lymphoma, Non-Hodgkin's Leukemia, T-Cell Leukemia, B-Cell||Drug: Dexamethasone Drug: Panobinostat Drug: Liposomal vincristine Drug: Mitoxantrone Drug: Peg-asparaginase Drug: Bortezomib Drug: Intrathecal Triples Drug: High-dose methotrexate Drug: 6-Mercaptopurine Drug: High-dose cytarabine Drug: Nelarabine Drug: Cyclophosphamide Drug: Etoposide Drug: Clofarabine||Phase 2|
This is a study of re-induction therapy that will comprise of three blocks of multi-agent chemotherapy. CR will be evaluated following each block of therapy. All patients will be candidates for hematopoietic stem cell transplant (HSCT) once they achieve negative minimal residual disease (MRD). If patients cannot proceed to HSCT following Block A, they will continue therapy on Block B and Block C until ready for HSCT.
Three Block Induction:
Block A: approximately 5 weeks
- Dexamethasone 10 mg/m^2/day orally (PO) Days 1-8, 15-22 (Total 16 days)
- Panobinostat 24 mg/m^2/dose PO Day 2,4,6
- Liposomal vincristine (VSLI) 2.25 mg/m^2 no cap intravenously (IV) on Days 7, 14, 21, 28
- Mitoxantrone 10 mg/m^2 IV Day 7,14 (In the absence of peripheral blasts, Day 14 Mitoxantrone will be given if WBC ≥1000 and ANC ≥300)
- Peg-asparaginase 2500 units/m^2 on Days 9,23
- Bortezomib 1.3 mg/m^2 IV Days 16, 19, 23, 26
- Intrathecal Triples (IT) (intrathecal methotrexate/hydrocortisone/cytarabine) (ITMHA) Days 1, 7, 14, 21, 28. Additional ITs on Days 10 and 17 for patients with central nervous system (CNS) 2, 3 or traumatic tap with blasts
Block B: approximately 5 weeks
- High-dose methotrexate 8 g/m^2 IV over 24 hours (will not be given to patients with prior cranial irradiation) Day 1
- 6-mercaptopurine 50 mg/m^2 PO days 1-14
- ITMHA Day 1
- High-dose cytarabine 3 g/m^2 IV every 12 hours (Q12H) Days 15 and 16
Block C: approximately 3 weeks
- Nelarabine 650 mg/m^2/day IV Days 1-5 (Clofarabine 40 mg/m^2/day IV Days 1-5 will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II)
- Cyclophosphamide 300 mg/m^2 IV Days 1-5
- Etoposide 100 mg/m^2/day IV Days 1-5
Response evaluation is performed after the end of each treatment block. All patients should proceed to hematopoietic stem cell transplantation (HSCT) after achieving negative minimal residual disease (MRD) when a suitable donor is identified. Patients could continue on Block B and Block C if not ready for HSCT. If after completion of Block C, MRD is persistently positive, the plan will be discussed with the principal investigator and co-principal investigator and the transplant team. Enrollment on ongoing natural killer (NK) cell studies will be considered. For patients who require a second transplant, HAP3R (another clinical trial at St. Jude Children's Research Hospital) may be an option. Donor will be selected according to institutional practices and transplant regimens will be used according to institutional HSCT protocols and guidelines.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study Incorporating Panobinostat, Bortezomib and Liposomal Vincristine Into Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma|
|Actual Study Start Date :||November 23, 2016|
|Actual Primary Completion Date :||March 11, 2018|
|Actual Study Completion Date :||March 11, 2018|
Experimental: Study Participants
Participants with ALL will receive the following interventions in three treatment blocks:
Given orally (PO).
Other Name: Decadron®
Other Name: LBH589
Drug: Liposomal vincristine
For intravenous (IV) use only.
Other Name: Novantrone®
Given IV or intramuscularly (IM).
In case of allergy or intolerance to Peg-asparaginase, Erwinia L-asparaginase (Erwinase®) will be used. Erwinia L-asparaginase is given by either IV or IM injection.
Given by IV push over 3 to 5 seconds. For IV use only.
Drug: Intrathecal Triples
Given IT as ITMHA.
Drug: High-dose methotrexate
Given intrathecally (IT) or IV.
Other Name: HDMTX
Given PO at consistent time each day.
Drug: High-dose cytarabine
Given IT or IV.
Other Name: Cytoxan®
In case of etoposide reactions, IV etoposide phosphate (Etopophos®) will be used.
Clofarabine will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II.
- Complete Remission (CR) Rate [ Time Frame: At the end of each remission re-induction block C (approximately 13 weeks after start of therapy) ]All participants who start re-induction Block A therapy are considered evaluable. Any patient who at any time point achieves CR and goes to transplant is considered as a success; or any patient who successfully reaches the end of block C and achieves/remains in CR is considered a success; all other cases are considered as failure.
- Block A Minimal Residual Disease (MRD) [ Time Frame: At the end of Block A therapy (approximately 5 weeks after start of therapy) ]MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. 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.
- Block B Minimal Residual Disease (MRD) [ Time Frame: At the end of Block B therapy (approximately 10 weeks after start of therapy) ]MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. 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.
- Block C Minimal Residual Disease (MRD) [ Time Frame: At the end of Block C therapy (approximately 13 weeks after start of therapy) ]MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. 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.
- Proportion of Relevant Toxicities [ Time Frame: At the completion of therapy (up to approximately 5 months after the start of therapy) ]The toxicities of liposomal vincristine (VSLI) when used in combination with chemotherapy will be evaluated. Proportions (probabilities) of relevant toxicities will be estimated with point and interval estimates.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02518750
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Principal Investigator:||Sima Jeha, MD||St. Jude Children's Research Hospital|