E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of the study treatment as determined by the rate of complete remission (CR) and complete remission with incomplete blood count recovery (CRi) in adult subjects with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in second relapse or adult subjects with Philadelphia chromosome-negative ALL who failed two treatment lines of anti-leukemia chemotherapy. One of these leukemia free intervals must be defined as lasting ≥ 90 days. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate: - duration of CR and CRi - overall survival - safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥18 years. 2. Have Philadelphia chromosome-negative ALL or lymphoblastic lymphoma and be in second relapse or have failed two treatment lines of anti-leukemia chemotherapy. 3. Have histologically or cytologically proven ALL and ≥10% bone marrow blasts. If <10% bone marrow blasts, subject must have histologically or cytologically proven ALL and evaluable extramedullary disease. 4. Have achieved a complete response to at least one prior anti-leukemia therapy as defined by a leukemia-free interval of ≥ 90 days. 5. For patients with a prior history of stem cell transplantation, ≤Grade 1 active skin graft-versus-host disease. No active gastrointestinal or liver graft-versus-host disease. 6. ECOG performance status 0–3. 7. Patients must have normal renal and liver function as defined below within 14 days, inclusive, prior to study enrollment, unless the abnormality is considered attributable to leukemia: a. Total bilirubin ≤2.0 x institutional upper limit of normal (ULN), unless the patient has a known diagnosis of Gilbert’s disease. b. Aspartate transaminase (AST, SGOT) or alanine transaminase (ALT, SGPT) ≤3 x institutional ULN. c. Serum creatinine ≤2.0 g/dL or calculated estimated creatinine clearance ≥50 mL/min/1.73 m2 based on Cockcroft and Gault formula, unless renal dysfunction is considered due to hematologic malignancy. 8. Never received prior Marqibo treatment. 9. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to enrollment. 10. If female, the patient is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (e.g., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide or abstinence) from the Screening visit through 30 days after the last dose of Marqibo. 11. If male, the patient agrees to use an acceptable barrier method for contraception from the Screening visit through 30 days after the last dose of Marqibo. 12. Before enrollment, the patient is capable of understanding and complying with parameters as outlined in the protocol and able to sign a written informed consent according to ICH/GCP, and national/local regulations. |
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E.4 | Principal exclusion criteria |
1. Burkitt’s lymphoma or Burkitt's leukemia. 2. History of Philadelphia chromosome-positive ALL and/or BCR/ABL rearrangements documented by FISH or PCR. 3. Active CNS disease. History of treated CNS disease is allowable. The CNS disease must have resolved in order for the subject to be eligible. 4. Eligibility for stem cell transplantation. This implies that a suitable donor is readily available, the subject is willing to undergo stem cell transplantation, and the Investigator believes this is a better treatment option than Marqibo. This is at the Investigator’s discretion. 5. Treatment with any investigational agents or chemotherapy agents in the last 21 days before study entry, unless full recovery from side effects has occurred or the patient has rapidly progressing disease judged to be life threatening by the Investigator. 6. Patients receiving any other standard or investigational treatment for their leukemia. a. Intrathecal chemotherapy for CNS prophylaxis is allowable. b. The use of hydroxyurea (Hydrea®) to control leukocytosis is allowable but must be tapered off by Day 14 of Course 1. From Day 15 of Course 1 on through the end of study participation, hydroxyurea (Hydrea®) is not allowed. c. Systemic corticosteroids must have been tapered off, preferably before the start of study treatment, but no later than by Day 5 of Course 1. From Day 6 of Course 1 on through the end of study participation, systemic corticosteroids are not allowed. 7. Persistent chronic clinically significant toxicities from prior chemotherapy ≥Grade 2 (NCI CTCAE v3.0). 8. Persistent ≥Grade 2 active neuropathy (NCI CTCAE v3.0). 9. History of persistent ≥Grade 2 active neurologic disorders unrelated to chemotherapy (including demyelinating form of Charcot-Marie-Tooth syndrome, acquired demyelinating disorders, or other demyelinating condition). 10. Patients with a history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to vincristine or components of Marqibo. 11. Pregnant or breast-feeding women. 12. Active serious infection not controlled by oral or intravenous antibiotics or antifungals. 13. Known human immunodeficiency virus (HIV) status. 14. Any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities. 15. Any condition or circumstance which in the opinion of the Investigator would significantly interfere with the patient’s protocol compliance and put the patient at increased risk. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is complete remission (CR) plus complete remission with incomplete blood count recovery (CRi). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |