Purpose

This is a first-in-human, multi-center, open-label clinical study with separate dose escalation (Phase 1) and expansion (Phase 2) stages to assess preliminary safety, tolerability, and efficacy of the second generation oral XPO1 inhibitor KPT-8602 in patients with relapsed/refractory multiple myeloma (MM), metastatic colorectal cancer (mCRC), metastatic castration resistant prostate cancer (mCRPC), and higher risk myelodysplastic syndrome (HR-MDS). Dose escalation and dose expansion may be included for all parts of the study as determined by ongoing study results. This study is currently closed for enrollment for patients with relapsed/refractory multiple myeloma (MM), metastatic or colorectal cancer (mCRC), and metastatic castration resistant prostate cancer (mCRPC).

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Written informed consent obtained prior to any screening procedures and in accordance with federal, local, and institutional guidelines.
  2. Age ≥ 18 years.

Higher Risk Myelodysplastic Syndrome (Part F):

3. Documented diagnosis of MDS with 5-19% myeloblasts.

4. Patients should be intermediate-2 or high-risk MDS by International Prognostic Scoring System (IPSS).

5. Patients believed to be IPSS high risk, without clearly meeting IPSS categories above should be discussed with the medical monitor prior to enrolling.

6. HMA refractory patients including:

1. ≥ 2 cycles of azacitidine and/or decitabine or experimental agents (such as SGI-110 or ASTX727 or similar) with clear progressive disease (PD) (no count recovery with ≥50% increase in bone marrow blasts)

OR

2. ≥ 4 cycles of azacitidine and/or decitabine (or other hypomethylating therapy) with lack of improvement (no CR/CRi/PR/HI).

7. Patients receiving a stable dose of erythropoiesis-stimulating agent (ESA) for at least 1 month at the time of study entry may continue to receive ESA.

Exclusion Criteria

Patients in All Parts of the Study:

1. Major surgery within 4 weeks before C1D1.

2. Impaired cardiac function or clinically significant cardiac diseases.

3. Uncontrolled active severe systemic infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to C1D1.

4. Patients with known symptomatic brain metastasis.

5. Prior malignancies:

1. Patients in All Parts of the Study: Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (i.e. cervix) may enroll irrespective of the time of diagnosis.

2. Patients with Higher Risk MDS only: Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of enrollment.

INDICATION-SPECIFIC EXCLUSION CRITERIA

Higher risk Myelodysplastic Syndrome (Part F):

6. IPSS low or intermediate-1 risk MDS.

7. Evidence of transformation to AML by World Health Organization (WHO) (≥20% blasts in bone marrow or peripheral blood).

8. Patients receiving granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) within the 3 weeks prior to C1D1.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
KPT-8602
Relapsed/Refractory Multiple Myeloma (RRMM) - CLOSED TO ENROLLMENT Metastatic Colorectal Cancer (CRC) - CLOSED TO ENROLLMENT Relapsed/Refractory Metastatic Castration Resistant Prostate Cancer (mCRPC) - CLOSED TO ENROLLMENT Higher Risk Myelodysplastic Syndrome (MDS) - CLOSED TO ENROLLMENT Starting dose for CRC, mCRPC, MDS is 20 mg of KPT-8602
  • Drug: KPT-8602

More Details

NCT ID
NCT02649790
Status
Active, not recruiting
Sponsor
Karyopharm Therapeutics Inc

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.